Publications by authors named "Yeting Hu"

19 Publications

  • Page 1 of 1

Hierarchically Microstructure-Bioinspired Flexible Piezoresistive Bioelectronics.

ACS Nano 2021 Jun 15. Epub 2021 Jun 15.

Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. China.

The naturally microstructure-bioinspired piezoresistive sensor for human-machine interaction and human health monitoring represents an attractive opportunity for wearable bioelectronics. However, due to the trade-off between sensitivity and linear detection range, obtaining piezoresistive sensors with both a wide pressure monitoring range and a high sensitivity is still a great challenge. Herein, we design a hierarchically microstructure-bioinspired flexible piezoresistive sensor consisting of a hierarchical polyaniline/polyvinylidene fluoride nanofiber (HPPNF) film sandwiched between two interlocking electrodes with microdome structure. Ascribed to the substantially enlarged 3D deformation rates, these bioelectronics exhibit an ultrahigh sensitivity of 53 kPa, a pressure detection range from 58.4 to 960 Pa, a fast response time of 38 ms, and excellent cycle stability over 50 000 cycles. Furthermore, this conformally skin-adhered sensor successfully demonstrates the monitoring of human physiological signals and movement states, such as wrist pulse, throat activity, spinal posture, and gait recognition. Evidently, this hierarchically microstructure-bioinspired and amplified sensitivity piezoresistive sensor provides a promising strategy for the rapid development of next-generation wearable bioelectronics.
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http://dx.doi.org/10.1021/acsnano.1c01606DOI Listing
June 2021

Dicer1 Promotes Colon Cancer Cell Invasion and Migration Through Modulation of tRF-20-MEJB5Y13 Expression Under Hypoxia.

Front Genet 2021 8;12:638244. Epub 2021 Mar 8.

Department of Colorectal Surgery, 4th Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Hypoxia plays a key role in colorectal cancer (CRC) metastasis, but its underlying mechanism remains largely unknown. Dicer1, an RNase, has been considered as a tumor regulator in many tumors. However, whether Dicer1 affects CRC progression under hypoxia remains uncertain. In this study, we found that Dicer1 expression was induced by hypoxia in CRC cells and it mediates hypoxia-induced CRC cell progression. Furthermore, we found that the expression of tRF-20-MEJB5Y13, a small non-coding RNA derived from tRNA, was increased under hypoxic conditions, and its upregulation by Dicer1 resulted in hypoxia-induced CRC cell invasion and migration. These results advance the current understanding of the role of Dicer1 in regulating hypoxia signals and provide a new pathway for the development of therapeutic interventions for inhibiting cancer progression.
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http://dx.doi.org/10.3389/fgene.2021.638244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982525PMC
March 2021

Prognostic Risk Model of Immune-Related Genes in Colorectal Cancer.

Front Genet 2021 4;12:619611. Epub 2021 Mar 4.

Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Purpose: We focused on immune-related genes (IRGs) derived from transcriptomic studies, which had the potential to stratify patients' prognosis and to establish a risk assessment model in colorectal cancer.

Summary: This article examined our understanding of the molecular pathways associated with intratumoral immune response, which represented a critical step for the implementation of stratification strategies toward the development of personalized immunotherapy of colorectal cancer. More and more evidence shows that IRGs play an important role in tumors. We have used data analysis to screen and identify immune-related molecular biomarkers of colon cancer. We selected 18 immune-related prognostic genes and established models to assess prognostic risks of patients, which can provide recommendations for clinical treatment and follow-up. Colorectal cancer (CRC) is a leading cause of cancer-related death in human. Several studies have investigated whether IRGs and tumor immune microenvironment (TIME) could be indicators of CRC prognoses. This study aimed to develop an improved prognostic signature for CRC based on IRGs to predict overall survival (OS) and provide new therapeutic targets for CRC treatment. Based on the screened IRGs, the Cox regression model was used to build a prediction model based on 18-IRG signature. Cox regression analysis revealed that the 18-IRG signature was an independent prognostic factor for OS in CRC patients. Then, we used the TIMER online database to explore the relationship between the risk scoring model and the infiltration of immune cells, and the results showed that the risk model can reflect the state of TIME to a certain extent. In short, an 18-IRG prognostic signature for predicting CRC patients' survival was firmly established.
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http://dx.doi.org/10.3389/fgene.2021.619611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970128PMC
March 2021

Alterations of circulating bacterial DNA in colorectal cancer and adenoma: A proof-of-concept study.

Cancer Lett 2021 02 27;499:201-208. Epub 2020 Nov 27.

Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Cancer Center Zhejiang University, Zhejiang, China. Electronic address:

The gut microbiota is closely associated with colorectal neoplasia. While most metagenomics studies utilized fecal samples, circulating bacterial DNA in colorectal neoplasia patients remained unexplored. This proof-of-concept study aims to characterize alterations of circulating bacterial DNA in colorectal neoplasia patients. We performed WGS of plasma samples from 25 colorectal cancer (CRC) patients, 10 colorectal adenoma (CRA) patients and 22 healthy controls (HC). Bacterial relative abundance was measured by removing the host genome and mapping reads into bacterial genomes. By diversity analysis, we found plasma samples required less sample size to approach saturation than fecal samples, and species diversity in HC was slightly higher compared with CRC/CRA patients. The majority of circulating bacterial DNA came from bacterial genera which commonly associated with gastrointestine and oral tract. By differential analysis, a total of 127 significant species between CRC patients and HC were identified, on which basis 28 species with top predictive ability were selected and showed promise in preliminary discrimination between CRC/CRA and HC. In CRA patients, relative abundance of the selected 28 species more closely resembled those in CRC patients than HC. By comparing with fecal metagenomics studies, we found there was moderate positive correlation between fold changes of the overlapped fecal and circulating bacterial DNA. Finally, species correlation analysis revealed that CRC and HC displayed distinct patterns of species association. In conclusion, this study demonstrated alterations of circulating bacterial DNA in colorectal neoplasia patients, which had the potential to become non-invasive biomarkers for colorectal neoplasia screening and early diagnosis.
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http://dx.doi.org/10.1016/j.canlet.2020.11.030DOI Listing
February 2021

Silencing of brain-expressed X-linked 2 (BEX2) promotes colorectal cancer metastasis through the Hedgehog signaling pathway.

Int J Biol Sci 2020 1;16(2):228-238. Epub 2020 Jan 1.

Department of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.

The incidence of colorectal cancer is increasing, and cancer metastasis is one of the major causes of poor outcomes. BEX2 has been reported to be involved in tumor development in several types of cancer, but its role in metastatic colorectal cancer remains largely undefined. Herein, we demonstrated that BEX2 knockout resulted in enhanced migratory and metastatic potential in colorectal cancer cells both in vitro and in vivo, and re-expression of BEX2 in knockout cells could reverse the enhanced migratory capacity. RNA-Seq results indicated that the hedgehog signaling pathway was activated after BEX2 knockout; moreover, the hedgehog signaling inhibitors, GANT61 and GDC-0449 could reverse the migratory enhancement of BEX2-/- colorectal cancer cells. We also demonstrated that the nuclear translocation of Zic2 after BEX2 silencing could activate the hedgehog signaling pathway, while Zic2 knockdown abrogated the migratory enhancement of BEX2-/- cells and inhibited the hedgehog signaling pathway. In summary, our findings suggest that BEX2 negatively modulates the hedgehog signaling pathway by retaining Zic2 in the cytoplasm in colorectal cancer cells, thereby inhibiting migration and metastasis of colorectal cancer cells.
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http://dx.doi.org/10.7150/ijbs.38431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949152PMC
November 2020

High-risk Stage III colon cancer patients identified by a novel five-gene mutational signature are characterized by upregulation of IL-23A and gut bacterial translocation of the tumor microenvironment.

Int J Cancer 2020 04 27;146(7):2027-2035. Epub 2019 Nov 27.

Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The heterogeneities of colorectal cancer (CRC) lead to staging inadequately of patients' prognosis. Here, we performed a prognostic analysis based on the tumor mutational profile and explored the characteristics of the high-risk tumors. We sequenced 338 colorectal carcinomas as the training dataset, constructed a novel five-gene (SMAD4, MUC16, COL6A3, FLG and LRP1B) prognostic signature, and validated it in an independent dataset from The Cancer Genome Atlas (TCGA). Kaplan-Meier and Cox regression analyses confirmed that the five-gene signature is an independent predictor of recurrence and prognosis in patients with Stage III colon cancer. The mutant signature translated to an increased risk of death (hazard ratio = 2.45, 95% confidence interval = 1.15-5.22, p = 0.016 in our dataset; hazard ratio = 4.78, 95% confidence interval = 1.33-17.16, p = 0.008 in TCGA dataset). RNA and bacterial 16S rRNA sequencing of high-risk tumors indicated that mutations of the five-gene signature may lead to intestinal barrier integrity, translocation of gut bacteria and deregulation of immune response and extracellular related genes. The high-risk tumors overexpressed IL23A and IL1RN genes and enriched with cancer-related bacteria (Bacteroides fragilis,Peptostreptococcus, Parvimonas, Alloprevotella and Gemella) compared to the low-risk tumors. The signature identified the high-risk group characterized by gut bacterial translocation and upregulation of interleukins of the tumor microenvironment, which was worth further researching.
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http://dx.doi.org/10.1002/ijc.32775DOI Listing
April 2020

Extent of enhancement on multiphase contrast-enhanced CT images is a potential prognostic factor of stage I-III colon cancer.

Eur Radiol 2019 Mar 25;29(3):1114-1123. Epub 2018 Sep 25.

Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, Zhejiang Province, China.

Objective: By evaluating extent of tumour enhancement on preoperative contrast-enhanced MDCT, we aimed to establish an imaging-based model to predict cancer-specific survival in stage I-III colon cancer.

Methods: A total of 548 stage I-III colon cancer patients who underwent curative resection from 2007 to 2013 were retrospectively included and divided into primary cohort and validation cohort according to admission time. The attenuation coefficient of each colon cancer was measured on the workstation by drawing the ROI in CT images. The enhancement ratio was calculated using maximum tumour attenuation value in triphasic MDCT scanning divided by the minimum. Patients were divided into low/high-enhancement groups according to the optimal cut-off value derived from time-dependent ROC curve. Kaplan-Meier method and COX regression analysis were adopted to evaluate prognostic value of variables. A nomogram for prognosis was conducted on the basis of a multivariate Cox proportional hazard model.

Results: No significant differences were observed in age, sex, pTNM stage, perioperative chemoradiotherapy, serum CEA, tumour size, tumour localisation and histologic type between low- and high-enhancement groups. The high-enhancement group had a significantly shorter cancer-specific survival rate (69.5%) than the low-enhancement group (85.9%) (p < 0.001). Subgroup analysis indicated that high-enhancement state was closely associated with increased risk of colon cancer mortality in stage I (p = 0.033), stage II (p = 0.002) and stage III (p = 0.014). Cox regression analysis indicated the extent of enhancement was an independent prognostic factor (HR 2.258, 95% CI 1.476-3.455; p < 0.001).

Conclusions: The extent of tumour enhancement on MDCT can serve as a potential risk factor for stage I-III colon cancer.

Key Points: • Survival rates of stage I-III colon cancer vary widely even within the same stage. • Prognostic value of the extent of tumour enhancement on MDCT was assessed. • The high-enhancement group had a significantly shorter cancer-specific survival rate.
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http://dx.doi.org/10.1007/s00330-018-5689-3DOI Listing
March 2019

A modified TNM staging system for non-metastatic colorectal cancer based on nomogram analysis of SEER database.

BMC Cancer 2018 01 8;18(1):50. Epub 2018 Jan 8.

Department of surgical oncology, and The Key Laboratory of Cancer Prevention and Intervention, Second Affiliated Hospital, China National Ministry of Education, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, Zhejiang Province, 310009, China.

Background: To revise the American Joint Committee on Cancer TNM staging system for colorectal cancer (CRC) based on a nomogram analysis of Surveillance, Epidemiology, and End Results (SEER) database, and to prove the rationality of enhancing T stage's weighting in our previously proposed T-plus staging system.

Methods: Total 115,377 non-metastatic CRC patients from SEER were randomly grouped as training and testing set by ratio 1:1. The Nomo-staging system was established via three nomograms based on 1-year, 2-year and 3-year disease specific survival (DSS) Logistic regression analysis of the training set. The predictive value of Nomo-staging system for the testing set was evaluated by concordance index (c-index), likelihood ratio (L.R.) and Akaike information criteria (AIC) for 1-year, 2-year, 3-year overall survival (OS) and DSS. Kaplan-Meier survival curve was used to valuate discrimination and gradient monotonicity. And an external validation was performed on database from the Second Affiliated Hospital of Zhejiang University (SAHZU).

Results: Patients with T1-2 N1 and T1N2a were classified into stage II while T4 N0 patients were classified into stage III in Nomo-staging system. Kaplan-Meier survival curves of OS and DSS in testing set showed Nomo-staging system performed better in discrimination and gradient monotonicity, and the external validation in SAHZU database also showed distinctly better discrimination. The Nomo-staging system showed higher value in L.R. and c-index, and lower value in AIC when predicting OS and DSS in testing set.

Conclusion: The Nomo-staging system showed better performance in prognosis prediction and the weight of lymph nodes status in prognosis prediction should be cautiously reconsidered.
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http://dx.doi.org/10.1186/s12885-017-3796-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759792PMC
January 2018

ANGPTL1 attenuates colorectal cancer metastasis by up-regulating microRNA-138.

J Exp Clin Cancer Res 2017 06 12;36(1):78. Epub 2017 Jun 12.

Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.

Background: Angiopoietin-like protein 1 (ANGPTL1) has been reported to suppress migration and invasion in lung and breast cancer, acting as a novel tumor suppressor candidate. Nevertheless, its effects on colorectal cancer (CRC) remain poorly defined. In this study, we aim to demonstrate the biological function of ANGPTL1 in CRC cells.

Methods: We explored ANGPTL1 mRNA expression in human CRC tissues and its association with prognosis. CRC cell lines overexpressing ANGPTL1 or with ANGPTL1 knocked down were constructed and analyzed for changes in proliferation, colony formation, migration and invasion. ANGPTL1-regulated microRNAs were analyzed, and microRNA inhibitor and mimics were used to explore the role of microRNA in ANGPTL1-associated biological function.

Results: ANGPTL1 mRNA expression was down-regulated in CRC tissues, and high ANGPTL1 expression predicted better survival in CRC patients. ANGPTL1 overexpression resulted in suppressed migration and invasion in vitro, and it prolonged overall survival in mouse models. By contrast, its down-regulation enhanced migration and invasion of CRC cells. MicroRNA-138 expression was positively correlated with ANGPTL1 mRNA level in CRC tissues and up-regulated by ANGPTL1 in CRC cells. In addition, the microRNA-138 inhibitor or mimics could reverse or promote the ANGPTL1-mediated inhibition of the migratory capacity of CRC cells, respectively.

Conclusions: This study is the first to demonstrate the biological function of ANGPTL1 in CRC cells. ANGPTL1 expression was down-regulated in CRC tissues and inversely correlated with poor survival. ANGPTL1 repressed migration and invasion of CRC cells, and microRNA-138 was involved in this process.
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http://dx.doi.org/10.1186/s13046-017-0548-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467265PMC
June 2017

Neuroendocrine differentiation is predictive of poor survival in patients with stage II colorectal cancer.

Oncol Lett 2017 Apr 7;13(4):2230-2236. Epub 2017 Feb 7.

Department of Surgical Oncology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang 310009, P.R. China.

The diagnosis of neuroendocrine differentiation (NED) is made primarily on the basis of ultrastructure and/or immunohistochemistry (IHC). Synaptophysin (Syn) and chromogranin A (CgA) are two important frequently used NED markers in colorectal cancer (CRC). The association between NED and the prognosis of stage II CRC remains controversial. Administration of adjuvant chemotherapy remains challenging for stage II CRC. Identification of reliable factors that improve the selection of patients with stage II CRC at high risk following surgery is of great importance. A total of 151 cases of patients with stage II CRC who received radical surgery in The Second Affiliated Hospital of Zhejiang University (Hangzhou, China) between January 2002 and March 2011 were assayed for Syn and CgA using IHC, following which patients were classified as NED(+) or NED(-). Survival curves were constructed using the Kaplan-Meier estimator, and the prognostic value was determined using a log-rank test and Cox's regression test. In the 151 cases of stage II CRC examined, the incidence of NED was 34.44%. The overall survival of the NED(+) group was significantly less favorable than that of the NED(-) group (P=0.001). The 5-year survival rate was 68% for NED(+) (n=51) and 90% for NED(-) (n=97). The independent prognostic factors of survival of patients with stage II CRC following multivariate analysis were age ≥65 years (P=0.007) and NED-positivity (P=0.014). NED was revealed to be an independent factor of poor prognosis for patients with stage II CRC, which may offer potential for improved therapy stratification.
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http://dx.doi.org/10.3892/ol.2017.5681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403537PMC
April 2017

BEX2 promotes tumor proliferation in colorectal cancer.

Int J Biol Sci 2017 12;13(3):286-294. Epub 2017 Feb 12.

Department of Surgical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China;; Key Laboratory of Cancer Prevention and Intervention of the China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

BEX2 has been suggested to promote the tumor growth in breast cancer and glioblastoma, while inhibit the proliferation of glioma cells. Thus, the role of BEX2 in tumor was still in debate. Additionally, the biological functions of BEX2 in colorectal cancer (CRC) have not yet been clarified. Here, we reported that BEX2 was overexpressed in advanced CRC from both the GSE14333 database and fresh CRC tissue specimens, and positively correlated with clinical staging. Knockdown of BEX2 significantly decreased the proliferation of SW620 colorectal cancer cells, suppressed subcutaneous xenograft growth and enhanced the survival of mice with cecal tumors. These effects were mainly mediated by the JNK/c-Jun pathway. Knockdown of BEX2 inhibited JNK/c-Jun phosphorylation, while BEX2 overexpression activated JNK/c-Jun phosphorylation. Moreover, the administration of the JNK-specific inhibitor SP600125 to SW620 with BEX2 overexpression abolished the effect of BEX2 on SW620 cell proliferation. This study reveals that BEX2 promotes colorectal cancer cell proliferation via the JNK/c-Jun pathway, suggesting BEX2 as a potential candidate target for the treatment of CRC.
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http://dx.doi.org/10.7150/ijbs.15171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370436PMC
November 2017

Hormone receptor status may impact the survival benefit of surgery in stage iv breast cancer: a population-based study.

Oncotarget 2016 Oct;7(43):70991-71000

Department of Surgical Oncology, 2nd Hospital of Zhejiang University School of Medicine, Hangzhou, P.R. China.

Introduction: The role of surgery in stage IV breast cancer is controversial. We used the Surveillance, Epidemiology, and End Results database to explore the impact of surgery on the survival of patients with stage IV breast cancer.

Methods: In total, 10,441 eligible stage IV breast cancer patients from 2004 to 2008 were included. They were divided into four groups as follows: R0 group (patients who underwent primary site and distant metastatic site resection), primary site resection group, metastases resection group, and no resection group.

Results: The four groups achieved a median survival time (MST) of 51, 43, 31 and 21 months, respectively, P < 0.001. The Cox proportional hazards model showed that the R0 group, primary resection group and metastases resection group had a good survival benefit, with hazard ratios of 0.558 (95% CI, 0.471-0.661), 0.566 (95% CI, 0.557-0.625) and 0.782 (95% CI, 0.693-0.883), respectively. In the hormone receptor (HR)-positive population, the R0 group (MST = 66 m, 5-year OS = 54.1%) gained an additional survival benefit compared with the primary resection group (MST = 52 m; 5-year OS = 44.9%; P < 0.001). The metastases resection group (MST = 38 m; 5-year OS = 31.7%) survived longer than the no resection group (MST = 28 m; 5-year OS = 22.0%; P < 0.001). In the HR-negative population, the R0 group and primary resection group had a similar survival (P = 0.691), and the metastases resection group had a similar outcome to that of the no resection group (P = 0.526).

Conclusion: Patients who underwent surgery for stage IV breast cancer showed better overall survival than the no resection group. Cytoreductive surgery could provide a survival benefit in HR+ stage IV breast cancer; however, in the HR- population, extreme caution should be exercised when considering surgery.
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http://dx.doi.org/10.18632/oncotarget.11235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342604PMC
October 2016

Incidence, Surgical Treatment, and Prognosis of Anorectal Melanoma From 1973 to 2011: A Population-Based SEER Analysis.

Medicine (Baltimore) 2016 Feb;95(7):e2770

From the Department of Surgical Oncology (HC, YC, YL, JH, YH, QX, KD),The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou ,Zhejiang, China); and Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province) (HC, YC, YL, JH, YH, QX, WH, KD), The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Anorectal melanoma (AM) is a rare type of melanoma that accounts for 0.4% to 1.6% of total malignant melanomas. The incidence of AM increases over time, and it remains highly lethal, with a 5-year survival rate of 6% to 22%. Considering the rare nature of this disease, most studies on AM comprise isolated case reports and single-center trials, which could not provide comprehensive assessment of the disease. Therefore, we conducted a population-based study by using the Surveillance, Epidemiology, and End Results (SEER) program to provide the latest and best available evidence of AM.We extracted all cases of AM registered in the SEER database from 1973 to 2011 (April 2014 release) and calculated age-adjusted incidence. Only cases with active follow-up were included to predict factors associated with prognosis. Survival outcomes were also compared among different types of surgery.We identified 640 AM cases, which consisted of 265 rectal melanoma and 375 anal melanoma. The estimated annual incidence rates of AM per 1 million population were 0.259 in males and 0.407 in females, and it increased with advanced age and over time. Tumor stage and surgical treatment were independent predictors of survival. Results implied that surgery improved the prognosis of patients with local- and regional-stage AM but could not prolong the survival of patients with distant-stage AM. Moreover, the outcome of less extensive excision was not statistically different from that of more extensive excision.This study provides an up-to-date estimation of the incidence and prognosis of AM by using SEER data. The incidence of AM continuously increases over time, despite its rarity. This disease also exhibits poor prognosis. Thus, AM must be further investigated in future studies. We also recommend surgery as the optimal treatment for local- and regional-stage AM patients but not for those with distant metastasis.
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http://dx.doi.org/10.1097/MD.0000000000002770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998623PMC
February 2016

Prognostic significance of matrix metalloproteinase 7 immunohistochemical expression in colorectal cancer: a meta-analysis.

Int J Clin Exp Med 2015 15;8(3):3281-90. Epub 2015 Mar 15.

The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute Hangzhou, Zhejiang, China ; Second Affiliated Hospital of Zhejiang University, School of Medicine Hangzhou, Zhejiang, China.

Matrix metalloproteinase 7 (MMP-7) was speculated to have a key role in the development and progression of human cancer. Considerable studies investigated the relationship between its expression and survival in colorectal cancer (CRC), but inconsistent results were obtained. The clinical significance of MMP-7 overexpression in CRC remains controversial. Therefore, in this article, we conducted a meta-analysis to analyze the prognostic value of MMP-7 in CRC. We searched studies in PubMed, Medline, and Web of Science databases until August 2014 to find relevant studies. A total of six high-quality studies met the inclusion criteria and 1631 patients were included in our study. Combined hazard ratios (HRs) suggested that MMP-7 overexpression had an unfavorable impact on overall survival (HR = 1.83, 95% CI: 1.24-2.71). Subgroup and sensitivity analyses further validated the role of MMP-7 as a predictor for prognosis. In conclusion, MMP-7 overexpression detected by immunohistochemistry indicated worse prognosis in CRC and may help to guide clinical therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443051PMC
June 2015

Association between MutL homolog 1 polymorphisms and the risk of colorectal cancer: a meta-analysis.

J Cancer Res Clin Oncol 2015 Dec 19;141(12):2147-58. Epub 2015 May 19.

The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Hangzhou, Zhejiang, China.

Purpose: As one of the most essential components of mismatch repair system, MutL homolog 1 (MLH1) plays an increasingly implicated role in initiation and promotion of colorectal carcinogenesis, with germ-line mutations in different loci. However, whether a single genetic variant in MLH1 could predict the risk of cancer was still under doubt and recent studies yielded inconsistent results. Therefore, this meta-analysis aimed at investigating the association between MLH1 single-nucleotide polymorphisms (SNPs) and colorectal cancer (CRC) risks.

Methods: A systematic literature search of PubMed, MEDLINE, Web of Science and BIOSIS databases was performed to obtain all available SNPs and studies. We focused on three SNPs (rs1800734, rs1799977 and rs63750448) with the most included studies and conducted overall and subgroup analyses after data extraction.

Results: A total of 37,347, 29,114 and 2722 patients in case and control groups were meta-analyzed in four genetic models (AA vs. BB, AB vs. BB, AA+AB vs. BB and AA vs. BB+AB) for each SNP. The overall results suggested that the mutation in rs63750447 predicted a higher CRC risk (AB vs. BB: OR 2.283, 95 % CI 1.612-3.232, P = 0.000; AA+AB vs. BB: OR 2.291, 95 % CI 1.618-3.244, P = 0.000), while rs1800734 and rs1799977 were not associated with CRC risks. Subgroup analysis according to study area, quality score and genotyping technique revealed the similar results.

Conclusions: As the first meta-analysis reporting the association between rs63750448 and CRC risk, the A allele substitution might be a risk factor for CRC. Additionally, there was no persuasive evidence showing that SNPs of rs1800734 and rs1799977 were related to CRC susceptibility.
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http://dx.doi.org/10.1007/s00432-015-1976-4DOI Listing
December 2015

Intake of cruciferous vegetables is associated with reduced risk of ovarian cancer: a meta-analysis.

Asia Pac J Clin Nutr 2015 ;24(1):101-9

Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, China. Email:

Background: Epidemiological studies on the association between cruciferous vegetable (CV) consumption and the risk of ovarian cancer have demonstrated inconsistent results. We conducted a meta-analysis on CV consumption and ovarian cancer risk.

Methods: The relevant studies were identified by searching the Medline (Pubmed), Embase and Web of Science databases. The references of related articles and reviews up to October 2013 were also screened. The pooled relative risks (RRs) with 95% confidence intervals (CIs) for the highest versus the lowest CV consumption levels were calculated using a random-effects model. The heterogeneity and publication bias were also evaluated.

Results: Eight studies (4 case-control studies and 4 cohort studies) were identified and included in this meta-analysis. When all studies were pooled together, there was a significantly inverse association between CV consumption and the risk of ovarian cancer (RR: 0.89; 95% CI: 0.81-0.99). No significant heterogeneity or publication bias was found.

Conclusions: The findings from this study suggest that the consumption of CVs may reduce the risk of ovarian cancer. Further investigations are needed to confirm the clinical effect of CVs on ovarian cancer.
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http://dx.doi.org/10.6133/apjcn.2015.24.1.22DOI Listing
April 2015

Laparoscopic surgery contributes more to nutritional and immunologic recovery than fast-track care in colorectal cancer.

World J Surg Oncol 2015 Feb 4;13:18. Epub 2015 Feb 4.

Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University, School of Medicine, Zhejiang, China.

Background: Many clinical trials had repeatedly shown that fast-track perioperative care and laparoscopic surgery are both preferred in the treatment of colorectal cancer. But few studies were designed to explore the diverse biochemical impacts of the two counterparts on human immunologic and nutritional status.

Methods: Ninety-two cases of colorectal cancer patients meeting the inclusion criteria were randomized to four groups: laparoscopy with fast-track treatment (LAFT); open surgery with fast-track treatment (OSFT); laparoscopy with conventional treatment (LAC); open surgery with conventional treatment (OSC). Peripheral blood tests including nutritional factors (albumin, prealbumin, and transferrin), humoral immunologic factors (IgG, IgM, and IgA), and cellular immunologic factors (T and NK cells) were evaluated. Blood samples were collected preoperatively (baseline) and 12 and 96 h after surgery (indicated as POH12 and POH96, respectively).

Results: Albumin, transferrin, prealbumin, and IgG levels were the highest in the LAFT group for both POH12 and POH96 time intervals. Repeated measures (two-way ANOVA) indicated that the difference of albumin, transferrin, and IgG level were attributed to surgery type (P < 0.05) and not perioperative treatment (P > 0.05). Only in the laparoscopy-included groups, the relative albumin and IgG levels of POH96 were obviously higher than that of POH12.

Conclusion: Laparoscopic surgery accelerated postoperative nutrition and immune levels rising again while fast-track treatment retarded the drop of postoperative nutrition and immune levels. Laparoscopic surgery might play a more important role than fast-track treatment in the earlier postoperative recovery of nutritional and immunologic status. Combined laparoscopic surgery with fast-track treatment provided best postoperative recovery of nutrition and immune status. These results should be further compared with the clinical outcomes of our FTMDT trial (clinicaltrials.gov: NCT01080547).
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http://dx.doi.org/10.1186/s12957-015-0445-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337197PMC
February 2015

Neuroendocrine differentiation is a prognostic factor for stage II poorly differentiated colorectal cancer.

Biomed Res Int 2014 29;2014:789575. Epub 2014 Jun 29.

Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, Zhejiang 310009, China.

Neuroendocrine differentiation (NED) in colorectal cancer is an indistinct phenomenon and may define a new cancer subtype, especially in the poorly differentiated colorectal cancer (PDCRC). The clinical features of PDCRC with NED remain controversial, thus confusing the implementation of individualized treatment. This study included 171 patients who underwent surgery from 2000 to 2011 and had pathology-confirmed PDCRC. Each sample was examined by immunohistochemistry for the biological markers of NED, synaptophysin (Syn), and chromogranin (CgA). Patients with Syn(+) and/or CgA(+) cells were classified as NED(+); otherwise, they were NED(-). Data were collected for patients who were followed up for at least two years. NED(+) staining was present in 71 (41.5%) patients. The median survival time was 36.9 months. No survival differences existed between the NED(-) and NED(+) groups (P > 0.05). However, stage II NED(+) patients had a significantly worse prognosis than NED(-) patients (P = 0.018). For the NED(+) group, the median survival was 38.56 months, and the 5-year survival was 65%. For the NED(-) group, the median survival was 53.18 months, and the 5-year survival was 90%. NED is a common event in primary PDCRC. For stage II PDCRC, NED(+) indicates a poor prognosis.
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http://dx.doi.org/10.1155/2014/789575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100365PMC
March 2015

BEX1 promotes imatinib-induced apoptosis by binding to and antagonizing BCL-2.

PLoS One 2014 13;9(3):e91782. Epub 2014 Mar 13.

The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Hangzhou, Zhejiang, China; The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

An enhanced anti-apoptotic capacity of tumor cells plays an important role in the process of breakpoint cluster region/Abelson tyrosine kinase gene (BCR/ABL)-independent imatinib resistance. We have previously demonstrated that brain expressed X-linked 1 (BEX1) was silenced in secondary imatinib-resistant K562 cells and that re-expression of BEX1 can restore imatinib sensitivity resulting in the induction of apoptosis. However, the mechanism by which BEX1 executes its pro-apoptotic function remains unknown. We identified B-cell lymphoma 2 (BCL-2) as a BEX1-interacting protein using a yeast two-hybrid screen. The interaction between BEX1 and BCL-2 was subsequently confirmed by co-immunoprecipitation assays. Like BCL-2, BEX1 was localized to the mitochondria. The region between 33K and 64Q on BEX1 is important for its localization to the mitochondria and its ability to interact with BCL-2. Additionally, we found that this region is essential for BEX1-regulated imatinib-induced apoptosis. Furthermore, we demonstrated that the interaction between BCL-2 and BEX1 promotes imatinib-induced apoptosis by suppressing the formation of anti-apoptotic BCL-2/BCL-2-associated X protein (BAX) heterodimers. Our results revealed an interaction between BEX1 and BCL-2 and a novel mechanism of imatinib resistance mediated by the BEX1/BCL-2 pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091782PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3953594PMC
December 2015
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