Publications by authors named "Zhi-Xun Zhao"

11 Publications

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The Distinction of Clinicopathological Characteristics, Treatment Strategy and Outcome in Colorectal Cancer Patients With Synchronous vs. Metachronous Bone Metastasis.

Front Oncol 2020 19;10:974. Epub 2020 Jun 19.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bejing, China.

The impact of the timing of bone metastasis (BM) diagnosis on colorectal cancer (CRC) patients is unclear. Our study aimed to explore the differences in clinicopathological characteristics, treatments and prognosis between synchronous BM (SBM) and metachronous BM (MBM) from CRC. We retrospectively investigated clinical data of CRC patients with SBM or MBM from 2008 to 2017 at Chinese National Cancer Center. Cancer specific survival (CSS) after BM diagnosis was estimated using the Kaplan-Meier method. The multivariable COX regression model identified the prognostic factors of CSS. Finally, 63 CRC patients with SBM and 138 CRC patients with MBM were identified. Compared to SBM from CRC, MBM significantly was more involving multiple bone lesions (63.0 vs. 7.9%; < 0.001), and more frequently originated from rectal cancer (60.9 vs. 41.3%; = 0.033). The therapeutic strategies in SBM and MBM group were contrasted including systemic treatment, bisphosphonates, radiotherapy and metastasectomy for BM. 85.5% of patients in MBM group and 25.4% of patients in SBM group underwent primary tumor resection at initial diagnosis ( < 0.001). The median CSS was 11 months in both SBM and MBM group ( = 0.556), yet MBM patients developed from CRC in early AJCC stage presented obviously longer survival than those from advanced stage. Furthermore, patients could have improved CSS from primary tumor resection while there might be no survival benefit from targeted therapy in both SBM and MBM groups. Bisphosphonates was associated with a better CSS for patients with SBM, while radiotherapy for BM was related to a better CSS for patients with MBM. The CRC patients in SBM and MBM group represented different clinicopathological characteristics and treatment modalities, which affected the prognosis in different ways. Distinct consideration for CRC patients with SBM and MBM in clinical decision making is required.
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http://dx.doi.org/10.3389/fonc.2020.00974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318073PMC
June 2020

B7-H3 immune checkpoint expression is a poor prognostic factor in colorectal carcinoma.

Mod Pathol 2020 11 8;33(11):2330-2340. Epub 2020 Jun 8.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Although PD-1/PD-L1 immunotherapy has been used successfully in treating many cancers, metastatic colorectal cancer (CRC) patients are not as responsive. B7-H3 is a promising target for immunotherapy and we found it to have the highest expression among B7-CD28 family members in CRC. Thus, the aim of the present study was to investigate B7-H3 expression in a large CRC cohort. B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. B7-H3 (50.9%) was detected in more primary tumors than B7-H4 (29.1%) or PD-L1 (29.2%), and elevated B7-H3 expression was associated with advanced overall stage. Co-expression of B7-H3 only with B7-H4 or PD-L1 was infrequent in primary tumors (6.3%, 5.7%, respectively). Moreover, B7-H3 in primary tumors was positively correlated with their respective expression at metastatic sites (ρ = 0.631; p < 0.001). No significant relationships between B7-H4 and PD-L1 and survival were observed; however, B7-H3 overexpression in primary tumors was significantly related to decreased disease-free survival. A positive relationship between B7-H3 expression and high density CD45RO T cell was observed in primary tumors, whereas B7-H4 and PD-L1 overexpression were related to CD3 T-cell infiltration. In conclusion, compared with B7-H4 and PD-L1, B7-H3 expression exhibited a higher prevalence and was significantly related to aggressiveness, worse prognosis and CD45RO T-cell infiltration in primary tumors. Further exploration of this potential target of immunotherapy in CRC patients is warranted.
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http://dx.doi.org/10.1038/s41379-020-0587-zDOI Listing
November 2020

A prognostic index model to individually predict clinical outcomes for colorectal cancer with synchronous bone metastasis.

J Cancer 2020 11;11(15):4366-4372. Epub 2020 May 11.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bejing, China.

The prognosis of synchronous bone metastasis (BM) in colorectal cancer (CRC) is poor and rarely concerned. A clinical tool to evaluate the prognosis and clinical outcomes for BM would be attractive in current clinical practice. A total of 342 CRC patients with synchronous BM were identified from Surveillance, Epidemiology, and End Results (SEER) database. The cancer specific survival (CSS) was estimated with the Kaplan-Meier method. Prognostic factors were identified from multivariate Cox model, and the final clinical nomogram was developed to predict the CSS. The concordance index (C-index) was used to assess the discriminative ability. Calibration curves were provided to internally validate the performance of the nomogram. The nomogram finally consisted of 6 prognostic factors including age, tumor grade, AJCC N stage, carcinoembryonic antigen (CEA) levels, primary tumor resection and chemotherapy, which translated the effects of prognostic factors into certain scores to predict the 1-, 2- and 3-year CSS for the synchronous BM in CRC patients. The nomogram presented a good accuracy for predicting the CSS with the C-index of 0.742. The calibration of the nomogram predictions was also accurate. This nomogram was accurate enough to predict the CSS of CRC patients with synchronous BM using readily available clinicopathologic factors and could provide individualized clinical decisions for both physicians and patients.
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http://dx.doi.org/10.7150/jca.40921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255384PMC
May 2020

Joint effect of pre-operative anemia and perioperative blood transfusion on outcomes of colon-cancer patients undergoing colectomy.

Gastroenterol Rep (Oxf) 2020 Apr 9;8(2):151-157. Epub 2019 Aug 9.

Department of Surgery, Yale School of Medicine, New Haven, CT, USA.

Background: Both pre-operative anemia and perioperative (intra- and/or post-operative) blood transfusion have been reported to increase post-operative complications in patients with colon cancer undergoing colectomy. However, their joint effect has not been investigated. The purpose of this study was to evaluate the joint effect of pre-operative anemia and perioperative blood transfusion on the post-operative outcome of colon-cancer patients after colectomy.

Methods: We identified patients from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database 2006-2016 who underwent colectomy for colon cancer. Multivariate logistic regression analysis was employed to assess the independent and joint effects of anemia and blood transfusion on patient outcomes.

Results: A total of 35,863 patients-18,936 (52.8%) with left-side colon cancer (LCC) and 16,927 (47.2%) with right-side colon cancer (RCC)-were identified. RCC patients were more likely to have mild anemia (62.7%) and severe anemia (2.9%) than LCC patients (40.2% mild anemia and 1.4% severe anemia). A total of 2,661 (7.4%) of all patients (1,079 [5.7%] with LCC and 1,582 [9.3%] with RCC) received a perioperative blood transfusion. Overall, the occurrence rates of complications were comparable between LCC and RCC patients (odds ratio [OR]=1.01; 95% confidence interval [CI]=0.95-1.07; =0.750). There were significant joint effects of anemia and transfusion on complications and the 30-day death rate ( for interaction: 0.010). Patients without anemia who received a transfusion had a higher risk of any complications (LCC, OR=3.51; 95% CI=2.55-4.85; <0.001; RCC, OR=3.74; 95% CI=2.50-5.59; <0.001), minor complications (LCC, OR=2.54; 95% CI=1.63-3.97; <0.001; RCC, OR=2.27; 95% CI=1.24-4.15; =0.008), and major complications (LCC, OR=5.31; 95% CI=3.68-7.64; <0.001; RCC, OR=5.64; 95% CI=3.61-8.79; <0.001), and had an increased 30-day death rate (LCC, OR=6.97; 95% CI=3.07-15.80; <0.001; RCC, OR=4.91; 95% CI=1.88-12.85; =0.001) than patients without anemia who did not receive a transfusion.

Conclusions: Pre-operative anemia and perioperative transfusion are associated with an increased risk of post-operative complications and increased death rate in colon-cancer patients undergoing colectomy.
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http://dx.doi.org/10.1093/gastro/goz033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136710PMC
April 2020

Prognostic scoring system for synchronous brain metastasis at diagnosis of colorectal cancer: A population-based study.

World J Gastrointest Oncol 2020 Feb;12(2):195-204

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Background: Brain metastasis (BM) from colorectal cancer (CRC) is rarely encountered clinically, and its prognosis has not been fully evaluated.

Aim: To construct a scoring system and accurately predict the survival of patients with synchronous BM at diagnosis of CRC.

Methods: A retrospective study of 371 patients with synchronous BM from CRC was performed, using the data from 2010 to 2014 from the Surveillance, Epidemiology, and End Results database. Survival time and prognostic factors were statistically analyzed by the Kaplan-Meier method and Cox proportional hazards models, respectively. A scoring system was developed using the independent prognostic factors, and was used to measure the survival difference among different patients.

Results: For the 371 patients, the median overall survival was 5 mo, survival rates were 27% at 1 year and 11.2% at 2 years. Prognostic analysis showed that age, carcinoembryonic antigen level and extracranial metastasis to the liver, lung or bone were independent prognostic factors. A scoring system based on these three prognostic factors classified the patients into three prognostic subgroups (scores of 0-1, 2-3, and 4). The median survival of patients with scores of 0-1, 2-3 and 4 was 14, 5 and 2 mo, respectively ( < 0.001). Subgroup analysis showed that there were significant differences in prognosis among the groups. Score 2-3 0-1: hazard ratio (HR) = 2.050, 95%CI: 1.363-3.083; 0.001; score 4 0-1: HR = 3.721, 95%CI: 2.225-6.225; < 0.001; score 2-3 4: HR = 0.551, 95%CI: 0.374-0.812; = 0.003.

Conclusion: The scoring system effectively distinguishes long-term and short-term survivors with synchronous BM from CRC. These results are helpful in providing a reference for guiding therapy.
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http://dx.doi.org/10.4251/wjgo.v12.i2.195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031150PMC
February 2020

A clinical model to predict the risk of synchronous bone metastasis in newly diagnosed colorectal cancer: a population-based study.

BMC Cancer 2019 Jul 17;19(1):704. Epub 2019 Jul 17.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bejing, China.

Background: The early detection of synchronous bone metastasis (BM) in newly diagnosed colorectal cancer (CRC) affects its initial management and prognosis. A clinical model to individually predict the risk of developing BM would be attractive in current clinical practice.

Methods: A total of 55,869 CRC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, of whom 317 patients were diagnosed with synchronous BM. Risk factors for BM in CRC patients was identified using multivariable logistic regression. A weighted scoring system was built with beta-coefficients (P < 0.05). A random sample of 75% of the CRC patients was used to establish the risk model, and the remaining 25% was used to validate its accuracy of this model. The performance of risk model was estimated by receiver operating curve (ROC) analysis.

Results: The risk model consisted of 8 risk factors including rectal cancer, poorly-undifferentiation, signet-ring cell carcinoma, CEA positive, lymph node metastasis, brain metastasis, liver metastasis and lung metastasis. The areas under the receiver operating curve (AUROC) were 0.903 and 0.889 in the development and validation cohort. Patients with scores from 0 to 4 points had about 0.1% risk of developing BM, and the risk increased to about 30% in patients with scores ≥15 points.

Conclusions: This clinical risk model is accurate enough to identify the CRC patients with high risk of synchronous BM and to further provide more individualized clinical decision.
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http://dx.doi.org/10.1186/s12885-019-5912-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637577PMC
July 2019

GGN Promotes Tumorigenesis by Regulating Proliferation and Apoptosis in Colorectal Cancer.

Pathol Oncol Res 2019 Oct 5;25(4):1621-1626. Epub 2019 Feb 5.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang Dist., Beijing, 100021, China.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. GGN is a germ cell-specific gene, but its function in CRC has been rarely reported to date. The aim of this study was to investigate the potential role of GGN in CRC tumorigenesis. Therefore, in this study, we examined the expression of GGN in CRC cell lines and tissues and its effects on cellular proliferation and apoptosis. We then explored the underlying mechanism. Our results showed that GGN was significantly overexpressed in both CRC cell lines and tissues. Silencing GGN robustly inhibited proliferation of CRC cells, and it also promoted apoptosis of CRC cells. Moreover, knockdown of GGN inhibited the expression of p-Akt in CRC cells. Taken together, these results showed that knockdown of GGN inhibits proliferation and promotes apoptosis of CRC cells through the PI3K/Akt signaling pathway. Our findings revealed for the first time a potential oncogenic role for GGN in CRC progress. This finding may provide a unique perspective on how a germ cell-specific gene might serve as a biomarker, or even as a therapeutic target, for CRC.
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http://dx.doi.org/10.1007/s12253-019-00595-3DOI Listing
October 2019

Current practice patterns of preoperative bowel preparation in colorectal surgery: a nation-wide survey by the Chinese Society of Colorectal Cancer.

World J Surg Oncol 2018 Jul 9;16(1):134. Epub 2018 Jul 9.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The optimal preoperative bowel preparation for colorectal surgery remains controversial. However, recent studies have established that bowel preparation varies significantly among countries and even surgeons at the same institution. This survey aimed to obtain information on the current practice patterns of bowel preparation for colorectal surgery in China.

Methods: A paper-based survey was circulated to the members of the Chinese Society of Colorectal Cancer (CSCC). The survey responses were collected and analyzed. Statistical analysis was performed for all the categorical variables according to the responses to individual questions.

Results: Three hundred forty-one members completed the questionnaire. Regarding surgical practice, 203 (59.5%) performed > 50% of the colorectal operations laparoscopically or robotically; the use of mechanical bowel preparation (MBP) alone was significantly higher (63.5 vs 31.9%; P < 0.001). The respondents who performed > 200 colonic or rectal resections provided significantly more MBP alone (79.6 vs 39.1%, P < 0.001; 76.6 vs 43.2%, P < 0.001; respectively). Among hospitals with fewer than 500 beds, 52.4% of the respondents used MBP + oral antibiotics preparation (OAP) + enema, a significantly higher percentage than the respondents of hospitals with more than 500 beds (P < 0.001). Nearly 40% of the respondents prescribed OAP in regimens; meanwhile, 74.8% prescribed preoperative intravenous antibiotics.

Conclusions: The study demonstrates considerable variation among members from the CSCC. These findings should be considered when developing multicenter trials and to provide more definitive answers.
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http://dx.doi.org/10.1186/s12957-018-1440-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038260PMC
July 2018

Different effection of p.1125Val>Ala and rs11954856 in APC on Wnt signaling pathway.

Oncotarget 2017 Sep 5;8(41):70854-70864. Epub 2017 Aug 5.

Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China.

Colorectal cancer (CRC) is among the most common and fatal forms of solid tumors worldwide and more than two thirds of CRC and adenomas patients have gene mutations. APC is a key regulator in the Wnt/β-catenin signaling pathway but its roles in CRC remains to be elucidated. In this study, we compared genes between CRC patients and controls to determine possible associations of nucleotide changes in the gene with the pathways involved in CRC pathogenesis. All participants received physical and enteroscopic examinations. The gene was sequenced for 300 Chinese Han CRC patients and 411 normal controls, and the expression levels of genes in the signaling pathway were analyzed using Western Blotting. Statistical analyses were conducted using SPSS (version 19.0) software. We found that rs11954856 in the gene was associated with colorectal cancer and could increase the expression levels of , , , and genes in the pathway in the CRC patients, demonstrating the involvement of APC in the pathological processes leading to CRC.
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http://dx.doi.org/10.18632/oncotarget.20106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642601PMC
September 2017

Polymorphisms in the CHIT1 gene: Associations with colorectal cancer.

Oncotarget 2016 Jun;7(26):39572-39581

Genomics Research Center, State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin Medical University, Harbin, China.

Colorectal cancer (CRC) is one of the most common solid tumors worldwide, often associated with inflammation. The microbes in the human intestine have a key role in inflammations and CRC. Chitotriose renders growth advantage to some bacteria, especially some pathogens, and thus has a role in inflammations. The enzyme chitotriosidase, encoded by the CHIT1 gene of the host, may degrade chitotriose with different efficiencies depending on the alleles. We sequenced the CHIT1 gene for 320 Chinese Han CRC patients and 404 normal controls, and focused on variations rs61745299 and rs35920428 within the CHIT1 gene for their possible roles in CRC. Statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). Multiple sequence alignment was conducted using the Vector NTI, and protein expression levels were analyzed by western blotting. The two variations, rs61745299 and rs35920428 within the CDS region of CHIT1 gene, were associated with the risk of CRC (both with P values < 0.001). Western blotting analysis showed that the variations increased the expression levels of the CHIT1 and C-reaction protein genes in the cancer tissue. We conclude that the two variations of CHIT1, rs61745299 and rs35920428, increase expression of the gene and are associated with CRC in Chinese Han populations.
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http://dx.doi.org/10.18632/oncotarget.9138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129954PMC
June 2016

An outbreak of sheep pox associated with goat poxvirus in Gansu province of China.

Vet Microbiol 2012 May 25;156(3-4):425-8. Epub 2011 Nov 25.

State Key Laboratory of Veterinary Etiological Biology, Engineering Research Center of Biological Detection of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.

Three strains of Capripoxviruses (CaPVs) were isolated from an outbreak of sheep pox in Gansu province of China. They were analyzed by P32 gene-based molecular methods and a species-specific PCR based on the RPO30 gene. Two bands which are specific to goat poxvirus (GTPV) were observed after the PCR products of P32 gene were digested with the endonuclease of Hinf I. Moreover, an amplicon of 172 bp, which is specific to GTPV, was amplified from the viruses by using the RPO30 gene-based PCR. Sequence analysis of the P32 genes showed that three nucleotide bases for coding residue of aspartic acid which are located at 163-165 position of P32 gene of sheep poxvirus (SPPV) were absent, and six single nucleotide substitutions which are characteristic of GTPV were present. The viruses were genetically closer to GTPV strains and clustered into the GTPV branch of the phylogenetic tree constructed on the basis of the P32 gene. The results characterized the isolated viruses as GTPV. It is the first report of an outbreak of sheep pox associated with GTPV in China.
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http://dx.doi.org/10.1016/j.vetmic.2011.11.015DOI Listing
May 2012
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