Publications by authors named "Yuanqing Ye"

168 Publications

Predicting COVID-19 epidemiological trend by applying population mobility data in two-stage modeling.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Feb;50(1):68-73

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,Zhejiang University,Hangzhou 310003,China.

:To predict the epidemiological trend of coronavirus disease 2019 (COVID-19) by mathematical modeling based on the population mobility and the epidemic prevention and control measures. : As of February 8,2020,the information of 151 confirmed cases in Yueqing,Zhejiang province were obtained,including patients' infection process,population mobility between Yueqing and Wuhan,etc. To simulate and predict the development trend of COVID-19 in Yueqing, the study established two-stage mathematical models,integrating the population mobility data with the date of symptom appearance of confirmed cases and the transmission dynamics of imported and local cases. : It was found that in the early stage of the pandemic,the number of daily imported cases from Wuhan (using the date of symptom appearance) was positively associated with the number of population travelling from Wuhan to Yueqing on the same day and 6 and 9 days before that. The study predicted that the final outbreak size in Yueqing would be 170 according to the number of imported cases estimated by consulting the population number travelling from Wuhan to Yueqing and the susceptible-exposed-infectious-recovered (SEIR) model; while the number would be 165 if using the reported daily number of imported cases. These estimates were close to the 170,the actual monitoring number of cases in Yueqing as of April 27,2020. : The two-stage modeling approach used in this study can accurately predict COVID-19 epidemiological trend.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0043DOI Listing
February 2021

Impact of socioeconomic status,population mobility and control measures on COVID-10 development in major cities of China.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Feb;50(1):52-60

Yale School of Public Health,Yale University,New Haven 06520,Connecticut,USA.

:To evaluate the impact of socioeconomic status,population mobility,prevention and control measures on the early-stage coronavirus disease 2019 (COVID-19) development in major cities of China. : The rate of daily new confirmed COVID-19 cases in the 51 cities with the largest number of cumulative confirmed cases as of February 19,2020 (except those in Hubei province) were collected and analyzed using the time series cluster analysis. It was then assessed according to three aspects,that is, socioeconomic status,population mobility,and control measures for the pandemic. : According to the analysis on the 51 cities,4 development patterns of COVID-19 were obtained,including a high-incidence pattern (in Xinyu),a late high-incidence pattern (in Ganzi),a moderate incidence pattern (in Wenzhou and other 12 cities),and a low and stable incidence pattern (in Hangzhou and other 35 cities). Cities with different types and within the same type both had different scores on the three aspects. : There were relatively large difference on the COVID-19 development among different cities in China,possibly affected by socioeconomic status,population mobility and prevention and control measures that were taken. Therefore,a timely public health emergency response and travel restriction measures inside the city can interfere the development of the pandemic. Population flow from high risk area can largely affect the number of cumulative confirmed cases.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0028DOI Listing
February 2021

Impact of Wuhan lockdown on the spread of COVID-19 in China: a study based on the data of population mobility.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Feb;50(1):61-67

Department of Surgical Oncology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China.

This study aimed to quantitatively assess the effectiveness of the Wuhan lockdown measure on controlling the spread of coronavirus diesase 2019 (COVID-19). : Firstly,estimate the daily new infection rate in Wuhan before January 23,2020 when the city went into lockdown by consulting the data of Wuhan population mobility and the number of cases imported from Wuhan in 217 cities of Mainland China. Then estimate what the daily new infection rate would have been in Wuhan from January 24 to January 30th if the lockdown measure had been delayed for 7 days,assuming that the daily new infection in Wuhan after January 23 increased in a high,moderate and low trend respectively (using exponential, linear and logarithm growth models). Based on that,calculate the number of infection cases imported from Wuhan during this period. Finally,predict the possible impact of 7-day delayed lockdown in Wuhan on the epidemic situation in China using the susceptible-exposed-infectious-removed (SEIR) model. : The daily new infection rate in Wuhan was estimated to be 0.021%,0.026%,0.029%,0.033% and 0.070% respectively from January 19 to January 23. And there were at least 20 066 infection cases in Wuhan by January 23,2020. If Wuhan lockdown measure had been delayed for 7 days,the daily new infection rate on January 30 would have been 0.335% in the exponential growth model,0.129% in the linear growth model,and 0.070% in the logarithm growth model. Correspondingly,there would have been 32 075,24 819 and 20 334 infection cases travelling from Wuhan to other areas of Mainland China,and the number of cumulative confirmed cases as of March 19 in Mainland China would have been 3.3-3.9 times of the officially reported number. Conclusions: Timely taking city-level lockdown measure in Wuhan in the early stage of COVID-19 outbreak is essential in containing the spread of the disease in China.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0021DOI Listing
February 2021

Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation.

Nat Commun 2021 05 13;12(1):2788. Epub 2021 May 13.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Human ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis.
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http://dx.doi.org/10.1038/s41467-021-23075-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119676PMC
May 2021

Allostatic score and its associations with demographics, healthy behaviors, tumor characteristics, and mitochondrial DNA among breast cancer patients.

Breast Cancer Res Treat 2021 Jun 28;187(2):587-596. Epub 2021 Jan 28.

Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Introduction: Allostatic load (AL), a composite index, has been used to capture variation in life-course stresses. However, few studies have been carried out among breast cancer patients.

Methods: In this study, we examined the cross-sectional association of AL with demographics, healthy behaviors, tumor characteristics, and mitochondrial DNA copy number in breast cancer patients. The study used a sub-sample of 934 women with newly diagnosed breast cancer at M.D. Anderson from 2013 to 2018. To construct the AL score, the study used a battery of seventeen factors that represents the activity of five physiological systems: metabolic, cardiovascular, immunological, renal, and liver.

Results: AL was positively associated with the age of disease diagnosis (P = 0.002), and was higher in Black and Hispanic populations than White (P = 0.001 and 0.032, respectively). AL was also found more abundant in those who experienced marital dissolution (P = 0.006), lacked a college education (P = 0.045), currently smoked (P = 0.011), and had low levels of physical activity (P = 0.037) than their counterparts. The study then found that higher AL was associated with increased odds of having poorly differentiated tumors (Odds ratio (OR): 1.40, 95% confidence interval (CI): 1.28, 1.62). An additional significant association was observed between AL with estrogen receptor negative (ER-) (OR = 1.56, 95%CI: 1.02, 2.36) among Black patients. Finally, we observed a significant positive correlation between AL with leukocyte mitochondrial DNA copy number variation (P < 0.001).

Conclusions: We conclude AL is influenced by selected demographics and healthy behaviors, and further is correlated with tumor characteristics and mitochondrial DNA copy number in breast cancer patients.
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http://dx.doi.org/10.1007/s10549-021-06102-0DOI Listing
June 2021

The relationship between body-mass index and overall survival in non-small cell lung cancer by sex, smoking status, and race: A pooled analysis of 20,937 International lung Cancer consortium (ILCCO) patients.

Lung Cancer 2021 02 4;152:58-65. Epub 2020 Dec 4.

Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Introduction: The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC).

Methods: Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses.

Results: Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; p = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (p = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (p<0.001) and obese categories (p = 0.004) relative to the normal-BMI category, when compared to male ever-smokers.

Conclusion: Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships.
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http://dx.doi.org/10.1016/j.lungcan.2020.11.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042597PMC
February 2021

HIF3A DNA methylation, obesity and weight gain, and breast cancer risk among Mexican American women.

Obes Res Clin Pract 2020 Nov - Dec;14(6):548-553. Epub 2020 Oct 26.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Family Medicine and Population Health, School of Medicine, Virginia Commonwealth University, VA, USA. Electronic address:

Objective: In previous epigenome-wide association studies, Hypoxia inducible Factor 3 Alpha Subunit (HIF3A) DNA methylation has been reported to be associated with body mass index (BMI) and weight change. However, none of these studies have included Mexican Americans.

Methods: In the current study, we assessed levels of HIF3A methylation in 927 Mexican American women identified from Mano-A-Mano, the Mexican American Cohort study.

Results: Significantly higher methylation levels at three CpG sites (position 46801557, 46801642, and 46801699) were observed in obese women compared to non-obese women (P < 0.05). Furthermore, we found that elevated methylation levels at those three CpG sites were associated with significant weight gain (P < 0.05), defined as an increase in BMI by at least one category between the baseline and the follow-up, with a median follow-up time of 39 months. Then, using pre-diagnostic blood DNA samples, we found increased DNA methylation at CpG 46801642 to be associated with a 1.35-fold increased risk of breast cancer (Hazard Ratio (HR) = 1.35, 95% Confidence Interval (CI): 1.02, 3.01), with a median follow-up time of 127 months. Using the Cancer Genome Atlas (TCGA) data, we further found that levels of HIF3A were significantly higher-methylated and down-regulated in breast tumor than in normal tissues (P < 1 × 10 for both).

Conclusion: Thus, our results provide evidence to support the role of HIF3A in obesity, weight gain, and the development of breast cancer.
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http://dx.doi.org/10.1016/j.orcp.2020.10.001DOI Listing
October 2020

Validation of plasma metabolites associated with breast cancer risk among Mexican Americans.

Cancer Epidemiol 2020 12 30;69:101826. Epub 2020 Sep 30.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States.

In our previous breast cancer case control study in Hispanics, we found 14 metabolites whose levels differed between cases and controls. To validate the results, we carried out a nested case control study of 100 incident breast cancer and 100 matched healthy women identified from the Mano-A-Mano Mexican American Cohort study. With the adjustment of parity, education, birth place, language acculturation, BMI category, smoking, drinking, physical activity, and sitting time, 4 metabolites were associated with breast cancer risk: 3-hydroxyoctanoate (Odds ratio (OR) = 1.51, 95% confidence interval (CI): 1.10, 3.47), 3-hydroxybutyrate (BHBA) (OR = 1.42, 95%CI: 1.01, 3.72), linoleate (18:2n6) (OR = 1.39, 95% CI: 1.07, 4.04), and bilirubin (OR = 0.54, 95%CI: 0.42, 0.95). Then, we used 3 non-redundant metabolites, namely 3-hydroxyoctanoate, linoleate (18:2n6), and bilirubin, to generate a metabolic risk score. Increased metabolites risk score was associated with a 1.67-fold increased risk of breast cancer (OR = 1.67, 95%CI: 1.32, 3.94). And the significant association was more evident among those who were diagnosed with cancer earlier during the follow-up (≤ 5 years) than their counterparts. In conclusion, we identified four significant metabolites which may help elucidate metabolic pathways that contribute to breast carcinogenesis. Our findings warrant further replication efforts.
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http://dx.doi.org/10.1016/j.canep.2020.101826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710579PMC
December 2020

Immune checkpoint-related serum proteins and genetic variants predict outcomes of localized prostate cancer, a cohort study.

Cancer Immunol Immunother 2021 Mar 9;70(3):701-712. Epub 2020 Sep 9.

Center for Clinical Big Data and Analytics, Bioinformatics and Big Data, The Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Rd, Hangzhou, 310058, PR China.

Background: The clinical predictors and biological mechanisms for localized prostate cancer (PCa) outcomes remain mostly unknown. We aim to evaluate the role of serum immune-checkpoint-related (ICK) proteins and genetic variations in predicting outcomes of localized PCa.

Methods: We profiled the serum levels of 14 ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, 4-1BB, CD27, and CTLA-4) in 190 patients with localized PCa. The genotypes of 97 single nucleotide polymorphisms (SNPs) from 19 ICK-related genes were analyzed in an extended population (N = 1762). Meta-data from ArrayExpress and TCGA was employed to validate and to probe functional data. Patients were enrolled and tumor aggressiveness, biochemical recurrence (BCR), and progression information were obtained. Statistical analyses were performed analyzing associations between serum biomarkers, genotypes, mRNA and outcomes.

Results: We showed that serum (s)BTLA and sTIM3 levels were associated with PCa aggressiveness (P < 0.05). sCD28, sCD80, sCTLA4, sGITR, sHVEM and sIDO correlated with both BCR and progression risks (all P < 0.05). We further identified ICK variants were significantly associated with aggressiveness, BCR and progression. Among them, 4 SNPs located in CD80 (rs7628626, rs12695388, rs491407, rs6804441) were not only associated with BCR and progression risk, but also correlated with sCD80 level (P < 0.01). rs491407 was further validated in an independent cohort. The CD80 mRNA expression was associated with BCR (HR, 1.85, 95% CI 1.06-3.22, P = 0.03) in meta-analysis of validation cohorts.

Conclusion: We highlight the prognostic value of serum ICK-related proteins for predicting aggressiveness, BCR and progression of PCa. The genetic variations and mRNA expression in CD80 could be predictors and potential targets of localized PCa.
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http://dx.doi.org/10.1007/s00262-020-02718-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907032PMC
March 2021

Genetic associations of T cell cancer immune response-related genes with T cell phenotypes and clinical outcomes of early-stage lung cancer.

J Immunother Cancer 2020 08;8(2)

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States

Background: Recent advances in T cell-related immunotherapy have brought remarkable progress in the treatment of non-small cell lung cancer (NSCLC). However, whether and how genetic variations of T cell cancer immune response genes can influence clinical outcomes of NSCLC patients remain obscure.

Methods: In this multiphase study, we assessed 2450 single-nucleotide polymorphisms (SNPs) from 280 T cell cancer immune response-related genes in 941 early-stage NSCLC patients (discovery n=536; validation n=405) to analyze the variants' associations with outcomes and to observe the effects on T cell phenotypes.

Results: We found 14 SNPs in 10 genes were associated with NSCLC outcomes (p<0.05) in both phases. Among them, :rs1964986 was the most significant variant associated with recurrence risk after meta-analysis (HR 1.84, 95% CI 1.35 to 2.52, p=1.15E-04), while :rs10108662 was the most significant SNP associated with death risk (HR 1.87, 95% CI 1.40 to 2.51, p=2.17E-05). Analysis of unfavorable genotypes indicated cumulative effects on death and recurrence risks. Seven treatment-specific variants were found to predict opposite outcomes in surgery-only and surgery-plus-chemotherapy subgroups. Expression quantitative trait loci analysis indicated that six SNPs significantly correlated with their corresponding gene expression. T cells from high-risk subjects displayed reduced degranulation (p=0.02) and decreased cytotoxicity against cancer cells (p<0.01). Gene expression profile indicated increased IDO1 expression and decreased IL2, PRF and GZMB expression in high-risk subjects.

Conclusions: Genetic variations in T cell cancer immune response pathways can impact outcomes and may be served as predictors for treatment efficacy in early-stage NSCLC patients. The correlation between immune genotypes and T cell antitumor immunity suggests a biological link between host immune genetics and NSCLC prognosis.
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http://dx.doi.org/10.1136/jitc-2019-000336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412613PMC
August 2020

Patterns of racial/ethnic disparities in baseline health-related quality of life and relationship with overall survival in patients with colorectal cancer.

Qual Life Res 2020 Nov 3;29(11):2977-2986. Epub 2020 Jul 3.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: Racial disparities are evident in colorectal cancer (CRC) prognosis with black patients experiencing worse outcomes than Hispanics and whites, yet mediators of these disparities are not fully known. The aim of this study is to identify variables that contribute to racial/ethnic disparities in health-related quality of life (HR-QoL) and overall survival in CRC.

Methods: Using SF-12 questionnaires, we assessed HR-QoL in 1132 CRC patients by calculating their physical (PCS) and mental composite summary (MCS) scores. Associations between poor PCS/MCS and sociodemographic factors were estimated and survival differences were identified by race/ethnicity.

Results: Hispanic patients who never married were at greater risk of poor PCS (OR 2.69; 95% CI 1.11-6.49; P = 0.028) than were currently married patients. College education was associated with a decreased risk of poor PCS in Hispanic and white, but not black, patients. Gender was significantly associated with poor MCS among white patients only. CRC patients who reported a poor PCS or MCS had poor survival, with differences in median survival times (MSTs) by race. The effect of PCS was strongest in white CRC patients with a difference in overall MST of > 116 months between those with favorable versus poor physical HR-QoL. Black patients who reported poor Physical and Mental HR-QoL showed significant risk of a poor outcome.

Conclusion: These findings suggest that racial/ethnic disparities in CRC survival may be related to differences in HR-QoL. Identified mediators of HR-QoL could supplement current CRC management strategies to improve patients' survival.
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http://dx.doi.org/10.1007/s11136-020-02565-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606765PMC
November 2020

Author Correction: Personalized Risk Assessment in Never, Light, and Heavy Smokers in a prospective cohort in Taiwan.

Sci Rep 2020 Mar 23;10(1):5514. Epub 2020 Mar 23.

UC San Diego Moores Cancer Center, San Diego, California, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-62322-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090032PMC
March 2020

Genetic variants in epithelial-mesenchymal transition genes as predictors of clinical outcomes in localized prostate cancer.

Carcinogenesis 2020 08;41(8):1057-1064

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Epithelial-mesenchymal transition (EMT) plays a pivotal role in the progression of prostate cancer (PCa). However, little is known about genetic variants in the EMT pathway as predictors of aggressiveness, biochemical recurrence (BCR) and disease reclassification in localized PCa.

Patients And Methods: In this multistage study, we evaluated 5186 single nucleotide polymorphisms (SNPs) from 264 genes related to EMT pathway to identify SNPs associated with PCa aggressiveness and BCR in the MD Anderson PCa (MDA-PCa) patient cohort (N = 1762), followed by assessment of the identified SNPs with disease reclassification in the active surveillance (AS) cohort (N = 392).

Results: In the MDA-PCa cohort, 312 SNPs were associated with high D'Amico risk (P < 0.05), among which, 14 SNPs in 10 genes were linked to BCR risk. In the AS cohort, 2 of 14 identified SNPs (rs76779889 and rs7083961) in C-terminal Binding Proteins 2 gene were associated with reclassification risk. The associations of rs76779889 with different endpoints were: D'Amico high versus low, odds ratio [95% confidence interval (CI)] = 2.89 (1.32-6.34), P = 0.008; BCR, hazard ratio (HR) (95% CI) = 2.88 (1.42-5.85), P = 0.003; and reclassification, HR (95% CI) = 2.83 (1.40-5.74), P = 0.004. For rs7083961, the corresponding risk estimates were: D'Amico high versus low, odds ratio (95% CI) = 1.69 (1.12-2.57), P = 0.013; BCR, HR (95% CI) = 1.87 (1.15-3.02), P = 0.011 and reclassification, HR (95% CI) = 1.72 (1.09-2.72), P = 0.020. There were cumulative effects of these two SNPs on modulating these endpoints.

Conclusion: Genetic variants in EMT pathway may influence the risks of localized PCa's aggressiveness, BCR and disease reclassification, suggesting their potential role in the assessment and management of localized PCa.
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http://dx.doi.org/10.1093/carcin/bgaa026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422619PMC
August 2020

Comprehensive T cell repertoire characterization of non-small cell lung cancer.

Nat Commun 2020 01 30;11(1):603. Epub 2020 Jan 30.

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX, 77030, USA.

Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including non-small cell lung cancer (NSCLC). This requires a better understanding of the T cells in the lungs of patients with NSCLC. Here, we report T cell repertoire analysis in a cohort of 236 early-stage NSCLC patients. T cell repertoire attributes are associated with clinicopathologic features, mutational and immune landscape. A considerable proportion of the most prevalent T cells in tumors are also prevalent in the uninvolved tumor-adjacent lungs and appear specific to shared background mutations or viral infections. Patients with higher T cell repertoire homology between the tumor and uninvolved tumor-adjacent lung, suggesting a less tumor-focused T cell response, exhibit inferior survival. These findings indicate that a concise understanding of antigens and T cells in NSCLC is needed to improve therapeutic efficacy and reduce toxicity with immunotherapy, particularly adoptive T cell therapy.
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http://dx.doi.org/10.1038/s41467-019-14273-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992630PMC
January 2020

Soluble immune checkpoint-related proteins as predictors of tumor recurrence, survival, and T cell phenotypes in clear cell renal cell carcinoma patients.

J Immunother Cancer 2019 11 29;7(1):334. Epub 2019 Nov 29.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Immune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. With the exception of a few candidate biomarkers, the prognostic role of soluble immune checkpoint-related proteins in clear cell renal cell cancer (ccRCC) patients is largely uninvestigated.

Methods: We profiled the circulating levels of 14 immune checkpoint-related proteins panel (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, CD137, CD27 and CTLA-4) and their associations with the risk of recurrence and death in 182 ccRCC patients using a multiplex Luminex assay. Gene expression in tumors from a subset of participating patients (n = 47) and another 533 primary ccRCC from TCGA were analyzed to elucidate potential mechanisms. Our primary endpoint is overall survival; secondary endpoint is recurrence-free survival. Multivariate Cox proportional hazard model, unconditional logistic regression model, and Kaplan-Meier analysis were applied in the study.

Results: sTIM3 and sLAG3 were significantly associated with advanced (stage III) disease (P < 0.05). sPD-L2 was the strongest predictor of recurrence (HR 2.51, 95%CI 1.46-4.34, P = 9.33E-04), whereas high sBTLA and sTIM3 was associated with decreased survival (HR 6.02, 95%CI 2.0-18.1, P = 1.39E-03 and HR 3.12, 95%CI 1.44-6.75, P = 3.94E-03, respectively). Risk scores based on sTIM3 and sBTLA indicated that the soluble immune checkpoint-related proteins jointly predicted recurrence and death risks of ccRCC (P = 0.01 and 4.44E-04, respectively). Moreover, sLAG3 and sCD28 were found negatively correlated with cytolytic activity of T cells in tumors (rho = -0.31 and - 0.33, respectively).

Conclusions: Our study provides evidence that soluble immune checkpoint-related proteins may associate with advanced disease, recurrence and survival in ccRCC patients, which highlights the prognostic values of soluble immune checkpoint-related proteins. Future independent validation in prospective studies is warranted.
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http://dx.doi.org/10.1186/s40425-019-0810-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884764PMC
November 2019

Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways.

Hum Mol Genet 2020 01;29(1):70-79

Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

We previously identified five single nucleotide polymorphisms (SNPs) at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate two loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5662 cases and 9237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF] = 0.40) was associated with DLBCL risk [odds ratio (OR) = 0.83, P = 3.62 × 10-13]. rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5510 cases and 12 817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF = 0.45) was also associated with DLBCL risk (OR = 1.20, P = 2.31 × 10-12). This SNP is 29 426-bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.
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http://dx.doi.org/10.1093/hmg/ddz228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001601PMC
January 2020

Loss of Life Expectancy by 10 Years or More From Elevated Aspartate Aminotransferase: Finding Aspartate Aminotransferase a Better Mortality Predictor for All-Cause and Liver-Related than Alanine Aminotransferase.

Am J Gastroenterol 2019 09;114(9):1478-1487

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.

Objectives: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are 2 commonly ordered liver function tests, and ALT has long been considered more liver-specific than AST. Between the 2, the one which is better in predicting liver or non-liver-related mortality remains unsettled.

Methods: The cohort, 416,122 adults, came from a self-paying comprehensive health surveillance program during 1994-2008 and was followed up till 2008. Mortality came from National Death Index, with 10,412 deaths identified. Hazard ratios (HRs), computed by Cox model, and life expectancy, by life table method, were presented for 5 levels of AST and ALT with elevated AST or ALT defined as ≥40 IU/L. Liver disease included liver cancer and other liver conditions.

Results: There were 3 times more elevated ALT (15.4%) than AST (5.7%). However, those with elevated AST had higher mortality for all-cause (HR = 2.44), for liver disease (HR = 27.2), and for liver cancer (HR = 47.6) than its ALT counterparts (HR = 1.69, 10.8, and 20.2, respectively). Elevated AST also lost more years of life expectancy (10.2) than those lost by ALT (5.2) and larger than most common risks. Elevated AST had increased mortality from all cancers (HR = 3.57), stroke (HR = 1.36), respiratory diseases (HR = 1.34), and injuries (HR = 1.82), other than just liver disease. All-cause mortality remained significantly increased, when high risk groups were excluded, such as frequent drinkers, hepatitis carriers, those died from nonmedical conditions, those died in the first 3 years, or advanced fibrosis index based on 4 factors or aspartate transaminase-to-platelet ratio index. Results were consistent between those returned for second visits and those analyzed in initial visits.

Discussion: Those with elevated AST (≥40 IU/L) had life expectancy cut short by 10.2 years, doubled the number of years lost with elevated ALT. For all-cause and for liver-related mortality, AST was an important predictor, better than ALT.
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http://dx.doi.org/10.14309/ajg.0000000000000332DOI Listing
September 2019

Metabolic hormones and breast cancer risk among Mexican American Women in the Mano a Mano Cohort Study.

Sci Rep 2019 07 10;9(1):9989. Epub 2019 Jul 10.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

C-peptide, insulin, leptin, and other metabolic hormones are assumed to play roles in breast cancer development; though, results are inconsistent. In this prospective case-control study nested within the Mano a Mano Cohort Study, we assessed the risk of breast cancer with regard to plasma levels of c-peptide, gastric inhibitory polypeptide, insulin, leptin, monocyte chemoattractant protein-1, pancreatic polypeptide, and peptide YY. Among women followed for a median of 8.5 years, 109 breast cancer cases were identified and frequency-matched to 327 controls at a ratio of 1:3. Overall, only c-peptide was observed significantly associated with breast cancer risk. High c-peptide levels (≥ the median level of controls) were significantly associated with increased breast cancer risk (odds ratio [OR] = 1.39, 95% confidence interval [CI]: 1.01, 2.44). In an analysis of participants stratified by age, the significant association between c-peptide levels and breast cancer risk was evident in only women age ≥51 years (OR = 1.53, 95% CI: 1.02, 3.27). Among women age <51 years, high leptin levels were significantly associated with decreased breast cancer risk (OR = 0.49, 95% CI: 0.24, 0.82). Our findings suggest that selected metabolic hormones are associated with breast cancer development in Mexican American women.
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http://dx.doi.org/10.1038/s41598-019-46429-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620309PMC
July 2019

Sex specific associations in genome wide association analysis of renal cell carcinoma.

Eur J Hum Genet 2019 10 23;27(10):1589-1598. Epub 2019 Jun 23.

Russian N.N. Blokhin Cancer Research Centre, Moscow, Russian Federation.

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (OR) = 0.83 [95% CI = 0.78-0.89], P = 1.71 × 10 compared with female odds ratio (OR) = 0.98 [95% CI = 0.90-1.07], P = 0.68) and 12q23.3 (intergenic, OR = 0.75 [95% CI = 0.68-0.83], P = 1.59 × 10 compared with OR = 0.93 [95% CI = 0.82-1.06], P = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.
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http://dx.doi.org/10.1038/s41431-019-0455-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777615PMC
October 2019

Body Mass Index (BMI), BMI Change, and Overall Survival in Patients With SCLC and NSCLC: A Pooled Analysis of the International Lung Cancer Consortium.

J Thorac Oncol 2019 09 1;14(9):1594-1607. Epub 2019 Jun 1.

PLA Hospital, Beijing, China.

Introduction: The relationships between morbid obesity, changes in body mass index (BMI) before cancer diagnosis, and lung cancer outcomes by histology (SCLC and NSCLC) have not been well studied.

Methods: Individual level data analysis was performed on 25,430 patients with NSCLC and 2787 patients with SCLC from 16 studies of the International Lung Cancer Consortium evaluating the association between various BMI variables and lung cancer overall survival, reported as adjusted hazard ratios (aHRs) from Cox proportional hazards models and adjusted penalized smoothing spline plots.

Results: Overall survival of NSCLC had putative U-shaped hazard ratio relationships with BMI based on spline plots: being underweight (BMI < 18.5 kg/m; aHR = 1.56; 95% confidence interval [CI]:1.43-1.70) or morbidly overweight (BMI > 40 kg/m; aHR = 1.09; 95% CI: 0.95-1.26) at the time of diagnosis was associated with worse stage-specific prognosis, whereas being overweight (25 kg/m ≤ BMI < 30 kg/m; aHR = 0.89; 95% CI: 0.85-0.95) or obese (30 kg/m ≤ BMI ≤ 40 kg/m; aHR = 0.86; 95% CI: 0.82-0.91) was associated with improved survival. Although not significant, a similar pattern was seen with SCLC. Compared with an increased or stable BMI from the period between young adulthood until date of diagnosis, a decreased BMI was associated with worse outcomes in NSCLC (aHR = 1.24; 95% CI: 1.2-1.3) and SCLC patients (aHR=1.26 (95% CI: 1.0-1.6). Decreased BMI was consistently associated with worse outcome, across clinicodemographic subsets.

Conclusions: Both being underweight or morbidly obese at time of diagnosis is associated with lower stage-specific survival in independent assessments of NSCLC and SCLC patients. In addition, a decrease in BMI at lung cancer diagnosis relative to early adulthood is a consistent marker of poor survival.
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http://dx.doi.org/10.1016/j.jtho.2019.05.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734935PMC
September 2019

Correction to: Breast cancer risk in relation to plasma metabolites among Hispanic and African American women.

Breast Cancer Res Treat 2019 08;176(3):697

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

In the original publication of the article, the sixth author name Krita A. Zanetti was mistakenly included as co-author. The corrected author group is given in the correction article. The original article has been corrected.
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http://dx.doi.org/10.1007/s10549-019-05292-yDOI Listing
August 2019

Circulating obesity-driven biomarkers are associated with risk of clear cell renal cell carcinoma: a two-stage, case-control study.

Carcinogenesis 2019 10;40(10):1191-1197

Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital and Department of Epidemiology and Health Statistics School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Obesity is one of modifiable risk factors for clear cell renal cell cancer (ccRCC). We aim to identify the association between obesity-driven biomarkers and ccRCC risk. This is a retrospective, two-phase, case-control study involving 682 cases and 733 controls. Obesity-driven biomarkers [gastric inhibitory polypeptide (GIP), C-peptide, insulin, resistin, adipsin, peptide YY, pancreatic polypeptide, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1, monocyte chemoattractant protein 1, lipocalin2, leptin, adiponectin] were measured using the Milliplex method. Multivariate logistic regression was used to assess the associations between biomarkers and ccRCC risk. Results revealed that GIP, C-peptide, IL-6 and TNF-α levels were consistently distinct between cases and controls. These markers were significantly associated with ccRCC risk in both phases (except C-peptide). In the combined population, compared with individuals with low levels of the biomarkers, individuals with high level of GIP [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.40-0.67] had lower risk, whereas individuals with high levels of C-peptide (OR = 1.46, 95% CI: 1.15-1.87), IL-6 (OR = 2.20, 95% CI: 1.50-3.22), TNF-α (OR = 1.90, 95% CI: 1.49-2.43) had significantly higher risk. Stratified analysis showed consistent associations with ccRCC risk in most subgroups (P < 0.05). The risk score based on the IL-6, TNF-α and GIP was positively associated with ccRCC risk in a dose-response manner (P for trend = 2.18E-13). Data from The Cancer Genome Atlas indicate that insulin signaling, IL-6 signaling and TNF-α signaling were enhanced in tumors. Collectively, our study demonstrates the integrative effect of insulin resistance and inflammation in ccRCC development, which may elucidate the basis of association between obesity and carcinogenesis. Further confirmation in prospective cohort studies are warranted for clinical applications in prevention and precision medicine of ccRCC.
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http://dx.doi.org/10.1093/carcin/bgz074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797001PMC
October 2019

Unruptured intracranial aneurysm growth trajectory: occurrence and rate of enlargement in 520 longitudinally followed cases.

J Neurosurg 2019 Mar 1;132(4):1077-1087. Epub 2019 Mar 1.

2Department of Epidemiology, MD Anderson Cancer Center, University of Texas, Houston, Texas.

Objective: As imaging technology has improved, more unruptured intracranial aneurysms (UIAs) are detected incidentally. However, there is limited information regarding how UIAs change over time to provide stratified, patient-specific UIA follow-up management. The authors sought to enrich understanding of the natural history of UIAs and identify basic UIA growth trajectories, that is, the speed at which various UIAs increase in size.

Methods: From January 2005 to December 2015, 382 patients diagnosed with UIAs (n = 520) were followed up at UCLA Medical Center through serial imaging. UIA characteristics and patient-specific variables were studied to identify risk factors associated with aneurysm growth and create a predicted aneurysm trajectory (PAT) model to differentiate aneurysm growth behavior.

Results: The PAT model indicated that smoking and hypothyroidism had a large effect on the growth rate of large UIAs (≥ 7 mm), while UIAs < 7 mm were less influenced by smoking and hypothyroidism. Analysis of risk factors related to growth showed that initial size and multiplicity were significant factors related to aneurysm growth and were consistent across different definitions of growth. A 1.09-fold increase in risk of growth was found for every 1-mm increase in initial size (95% CI 1.04-1.15; p = 0.001). Aneurysms in patients with multiple aneurysms were 2.43-fold more likely to grow than those in patients with single aneurysms (95% CI 1.36-4.35; p = 0.003). The growth rate (speed) for large UIAs (≥ 7 mm; 0.085 mm/month) was significantly faster than that for UIAs < 3 mm (0.030 mm/month) and for males than for females (0.089 and 0.045 mm/month, respectively; p = 0.048).

Conclusions: Analyzing longitudinal UIA data as continuous data points can be useful to study the risk of growth and predict the aneurysm growth trajectory. Individual patient characteristics (demographics, behavior, medical history) may have a significant effect on the speed of UIA growth, and predictive models such as PAT may help optimize follow-up frequency for UIA management.
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http://dx.doi.org/10.3171/2018.11.JNS181814DOI Listing
March 2019

Breast cancer risk in relation to plasma metabolites among Hispanic and African American women.

Breast Cancer Res Treat 2019 Aug 15;176(3):687-696. Epub 2019 Feb 15.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Purpose: The metabolic etiology of breast cancer has been explored in the past several years using metabolomics. However, most of these studies only included non-Hispanic White individuals.

Methods: To fill this gap, we performed a two-step (discovery and validation) metabolomics profiling in plasma samples from 358 breast cancer patients and 138 healthy controls. All study subjects were either Hispanics or non-Hispanic African Americans.

Results: A panel of 14 identified metabolites significantly differed between breast cancer cases and healthy controls in both the discovery and validation sets. Most of these identified metabolites were lipids. In the pathway analysis, citrate cycle (TCA cycle), arginine and proline metabolism, and linoleic acid metabolism pathways were observed, and they significantly differed between breast cancer cases and healthy controls in both sets. From those 14 metabolites, we selected 9 non-correlated metabolites to generate a metabolic risk score. Increased metabolites risk score was associated with a 1.87- and 1.63-fold increased risk of breast cancer in the discovery and validation sets, respectively (Odds ratio (OR) 1.87, 95% Confidence interval (CI) 1.50, 2.32; OR 1.63, 95% CI 1.36, 1.95).

Conclusions: In summary, our study identified metabolic profiles and pathways that significantly differed between breast cancer cases and healthy controls in Hispanic or non-Hispanic African American women. The results from our study might provide new insights on the metabolic etiology of breast cancer.
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http://dx.doi.org/10.1007/s10549-019-05165-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588417PMC
August 2019

Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer: A Mendelian Randomization Analysis.

Cancer Epidemiol Biomarkers Prev 2019 05 30;28(5):935-942. Epub 2019 Jan 30.

Research Unit of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear.

Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk.

Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall non-small cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15-2.27; = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; = 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings.

Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention.

Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-0356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075698PMC
May 2019

The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study.

PLoS Med 2019 01 3;16(1):e1002724. Epub 2019 Jan 3.

National Institute of Public Health, Bucharest, Romania.

Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.

Methods And Findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.

Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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http://dx.doi.org/10.1371/journal.pmed.1002724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317776PMC
January 2019

Genetic associations of T cell cancer immune response with tumor aggressiveness in localized prostate cancer patients and disease reclassification in an active surveillance cohort.

Oncoimmunology 2019;8(1):e1483303. Epub 2018 Oct 29.

Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Determining prostate cancer (PCa) aggressiveness and reclassification are critical events during the treatment of localized disease and for patients undergoing active surveillance (AS). Since T cells play major roles in cancer surveillance and elimination, we aimed to identify genetic biomarkers related to T cell cancer immune response which are predictive of aggressiveness and reclassification risks in localized PCa. The genotypes of 3,586 single nucleotide polymorphisms (SNPs) from T cell cancer immune response pathways were analyzed in 1762 patients with localized disease and 393 who elected AS. The aggressiveness of PCa was defined according to pathological Gleason score (GS) and D'Amico criteria. PCa reclassification was defined according to changes in GS or tumor characteristics during subsequent surveillance biopsies. Functional characterization and analysis of immune phenotypes were also performed. In the localized PCa cohort, seven SNPs were significantly associated with the risk of aggressive disease. In the AS cohort, another eight SNPs were identified as predictors for aggressiveness and reclassification. Rs1687016 of was the most significant predictor of reclassification. Cumulative analysis showed that a genetic score based on the identified SNPs could significantly predict risk of D'Amico high risk disease (= 2.4E-09), GS4 + 3 disease (= 1.3E-04), biochemical recurrence (= 0.01) and reclassification (= 0.01). In addition, the rs34309 variant was associated with functional somatic mutations in the PI3K/PTEN/AKT/MTOR pathway and tumor lymphocyte infiltration. Our study provides plausible evidence that genetic variations in T cell cancer immune response can influence risks of aggressiveness and reclassification in localized PCa, which may lead to additional biological insight into these outcomes. PCa, prostate cancer; AS, active surveillance; GS, Gleason score; PSA, prostate specific antigen; TCGA, The Cancer Genome Atlas; SNP, single nucleotide polymorphisms; UFG, unfavorable genotype.
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http://dx.doi.org/10.1080/2162402X.2018.1483303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287782PMC
October 2018

A 5-microRNA signature identified from serum microRNA profiling predicts survival in patients with advanced stage non-small cell lung cancer.

Carcinogenesis 2019 07;40(5):643-650

Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Circulating microRNAs (miRNAs) are potential biomarkers for cancer diagnosis, screening and prognosis. This study aimed to identify serum miRNAs as predictors of survival in patients with advanced non-small cell lung cancer (NSCLC). We profiled serum miRNAs in a pilot set of four patients with good survival (>24 months) and four patients with poor survival (<6 months). We selected 140 stably detectable miRNAs and 42 miRNAs reported in literature for further analysis. Expression of these 182 miRNAs was measured using high-throughput polymerase chain reaction assay, and their association with 3-year survival in the discovery (n = 345) and validation (n = 177) cohorts was assessed. Five serum miRNAs (miR-191, miR-28-3p, miR-145, miR-328 and miR-18a) were significantly associated with 3-year overall survival in both cohorts. A combined 5-miRNA risk score was created to assess the cumulative impact of these miRNAs on risk of death. Quartile analysis of the risk score showed significant association with 3-year death risk, with a 4.6-, 6.8- and 9.3-month reduction in median survival time for the second, third and fourth quartiles, respectively. Survival tree analysis also identified distinct risk groups with different 3-year survival durations. Data from The Cancer Genome Atlas revealed all five miRNAs were differentially expressed (P < 0.0001) in paired tumor and normal tissues. Pathway analysis indicated that target genes of these five miRNAs were mainly enriched in inflammatory/immune response pathways and pathways implicated in resistance to chemoradiotherapy and/or targeted therapy. Our results suggested that the 5-miRNA signature could serve as a prognostic predictor in patients with advanced NSCLC.
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http://dx.doi.org/10.1093/carcin/bgy132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610172PMC
July 2019

Serum miR-331-3p predicts tumor recurrence in esophageal adenocarcinoma.

Sci Rep 2018 09 18;8(1):14006. Epub 2018 Sep 18.

Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

MicroRNAs (miRNAs) may contribute to the initiation and progression of cancer. The role of circulating miRNAs as predictors of recurrence in esophageal adenocarcinoma (EAC) has not been extensively explored. Here we measured the expressions of 167 miRNAs in serum samples from a discovery cohort of 72 EAC patients (32 patients with recurrence and 40 patients without). A rank sum test was performed to identify differentially expressed miRNAs. Cox regression model was applied to estimate the effect of miRNA expression on recurrence-free survival. The eligible miRNAs were then validated in an independent cohort of 329 EAC patients (132 patients with recurrence and 197 patients without). miR-331-3p was identified and confirmed to be differentially expressed between EAC patients with and without recurrence and associated with recurrence-free survival. In both cohorts, the expression of miR-331-3p was consistently decreased in patients with recurrence compared to those without (P < 0.05). Using patients with low expression of miR-331-3p as reference, those with high expression had HRs for recurrence of 0.45 (95% CI, 0.21-0.96, P = 0.040) and 0.55 (95% CI, 0.38-0.78, P = 0.001) in the discovery and validation cohorts, respectively. Therefore, serum miR-331-3p may be a useful biomarker for identifying EAC patients at high risk of recurrence.
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http://dx.doi.org/10.1038/s41598-018-32282-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143616PMC
September 2018