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Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

World Journal of Gastroenterology 2018年第20期24卷 2181-2190页

作者： Wen-Juan Ma Xing Wang Wen-Ting Yan zhong-Guo Zhou zhi-zhong pan Gong Chen Rong-Xin Zhang State Key Laboratory of Oncology in South China Sun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina Collaborative Innovation Center of Cancer Medicine Guangzhou 510060Guangdong ProvinceChina Tongji Medical College Huazhong University of Science and TechnologyWuhan 430074Hubei ProvinceChina Department of Hepatobiliary Surgery Cancer CenterSun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina Department of Colorectal Surgery Cancer CenterSun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina

AIM To evaluate indoleamine-2,3-dioxygenase 1/cyclooxygenase 2(IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer(CRC) *** We retrospectively studied the medical records of 95 patients who received surgical resection from August 2008 to January 2010. All patients were randomly assigned to adjuvant treatment with or without celecoxib groups after surgery. We performed standard immunohistochemistry to assess the expression levels of IDO1/COX2 and evaluated the correlation of IDO1/COX2 with clinicopathological factors and overall survival(OS) *** The expression of nuclear IDO1 was significantly correlated with body mass index(P < 0.001), and IDO1 expression displayed no association with sex, age, tumor differentiation, T stage, N stage, carcinoembryonic antigen, cancer antigen 19-9, CD3+ and CD8+ tumor infiltrating lymphocytes, and COX2. In univariate analysis, we found that nuclear IDO1(P = 0.039), nuclear/cytoplasmic IDO1 [hazard ratio(HR) = 2.044, 95% confidence interval(CI): 0.871-4.798, P = 0.039], nuclear IDO1/COX2(HR = 3.048, 95%CI: 0.868-10.7, P = 0.0049) and cytoplasmic IDO1/COX2(HR = 2.109, 95%CI: 0.976-4.558, P = 0.022) all yielded significantly poor OS outcomes. Nuclear IDO1(P = 0.041), nuclear/cytoplasmic IDO1(HR = 3.023, 95%CI: 0.585-15.61, P = 0.041) and cytoplasmic IDO1/COX2(HR = 2.740, 95%CI: 0.764-9.831, P = 0.038) have significantly poor OS outcomes for the CRC celecoxib subgroup. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC(HR = 2.218, 95%CI: 1.011-4.48, P = 0.047) and celecoxib subgroup patients(HR = 3.210, 95%CI: 1.074-9.590, P = 0.037).CONCLUSION Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent poor predictor for OS in CRC.

关键词： Prognosis Indoleamine-2,3-dioxygenase 1 Cyclooxygenase 2 Colorectal cancer

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Using p53-immunostained large specimens to determine the distal intramural spread margin of rectal cancer

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World Journal of Gastroenterology 2006年第10期12卷 1626-1629页

作者： zhi-zhong pan De-Sen Wan Chang-Qing Zhang Jian-Yong Shao Li-Ren Li Gong Chen zhi-Wei Zhou Fu-Long Wang Department of Abdominal Surgery Cancer Hospital Sun Yat-Sen University Guangzhou 510060 Guangdong Province China

AIM： To determine the distal intramural spread （DIS） margin of rectal cancer.METHODS： Sixty-one p53-positive specimens of rectal cancer were used. After conventional hematoxylin and eosin （H＆E） staining, the DIS margin of rectal cancer in large specimens was examined by immunohistochemistry. The patients were divided into A, B, C, and D groups. After a long-term follow-up, the survival curves of the four groups were estimated using the life table. RESULTS： Fifty-one of the sixty-one cases （83.6%） had DIS. The extent of DIS ranged 0.11-3.5 cm; meanwhile *** of DIS measured by H＆E staining was 0.13 cm. The significant difference was found between the means （t=5.622, P〈0.0001）. Only 1 of 51 patients had DIS greater than 3 cm. The DIS was less than 1.0 cm in most rectal cancer patients. The long-term results indicated that the survival rate of the patients whose DIS was greater than 1.0 cm was lower than that of the patients whose DIS was less than 0.5 cm. CONCLUSION： Rectal cancer patients with DIS greater than 1.0 cm have poor prognosis.

关键词： Rectal cancer Distal intramural spread p53 Immunohistochemistry Large specimen

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Risk factors for sporadic colorectal cancer in southern Chinese

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World Journal of Gastroenterology 2009年第20期15卷 2526-2530页

作者： Yi-Sheng Wei Jia-Chun Lu Lei Wang Ping Lan Hong-Jun Zhao zhi-zhong pan Jun Huang Jian-Ping Wang Gastrointestinal Institute of Sun Yat-Sen University Department of Colorectal Surgery The Sixth Affiliated Hospital of Sun Yat-Sen University Guangzhou 510655 Guangdong Province China Institute for Chemical Carcinogenesis Guangzhou Medical College Guangzhou 510182 Guangdong Province China Department of Abdominal Surgery Sun Yat- Sen University Cancer Center Guangzhou 510060 Guangdong Province China

AIM:To investigate the role of smoking, alcohol drinking, family history of cancer, and body mass index(BMI) in sporadic colorectal cancer in southern ***:A hospital-based case-control study was conducted from July 2002 to December *** were 706 cases and 723 controls with their sex and age(within 5 years) *** unconditional logistic regression model was used to analyze the association between smoking, alcohol drinking, family history of cancer, BMI and sporadic colorectal ***:No positive association was observed between smoking status and sporadic colorectal cancer *** with the non alcohol drinkers, the current and former alcohol drinkers had an increased risk of developing sporadic colorectal cancer(CRC)(adjusted OR = 8.61 and 95% CI = 6.15-12.05;adjusted OR = 2.30, 95% CI = 1.27-4.17).Moreover, the increased risk of developing sporadic CRC was significant in those with a positive family history of cancer(adjusted OR = 1.62, 95% CI = 1.12-3.34) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.39, 95% CI = 1.10-1.75).Stratification analysis showed that the risk of developing both colon and rectal cancers was increased in current alcohol drinkers(adjusted OR = 7.60 and 95% CI = 5.13-11.25;adjusted OR = 7.52 and 95% CI = 5.13-11.01) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.38 and 95% CI = 1.04-1.83;adjusted OR = 1.35 and 95% CI = 1.02-1.79).The risk of developing colon cancer, but not rectal cancer, was found in former alcohol drinkers and in those with a positive family history of cancer(adjusted OR = 2.51 and 95% CI = 1.24-5.07;adjusted OR = 1.82 and 95% CI = 1.17-2.82).CONCLUSION:Alcohol drinking, high BMI(≥ 24.0 kg/m2) and positive family history of cancer are the independent risk factors for colorectal cancer in southern Chinese.

关键词： Case-control Colorectal cancer Risk factors Smoking Alcohol drinking Body mass index Family history

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Oxaliplatin-containing adjuvant chemotherapy improves the survival of locally advanced rectal cancer patients with pathological complete response after pre-operative chemoradiotherapy

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Gastroenterology Report 2018年第3期6卷 195-201,I0002页

作者： Jian-Hong Peng Jun-zhong Lin Yu-Ming Rong Ying Zhu Yu-Xiang Deng Yu-Jie Zhao Zhen-Hai Lu Xiao-Jun Wu zhi-zhong pan Department of Colorectal Surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine651 Dongfeng Road EastGuangzhouGuangdong 510060P.R.China VIP Region Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine651 Dongfeng Road EastGuangzhouGuangdong 510060P.R.China

Background:The necessity for adjuvant chemotherapy(ACT)in locally advanced rectal cancer(LARC)patients who achieve pathological complete response(pCR)after pre-operative chemoradiotherapy(CRT)is still not *** aimed to investigate the therapeutic value of ACT in these ***:Clinical data were retrospectively collected from 105 consecutive LARC patients who achieved pCR after pre-operative CRT and underwent radical tumor resection between December 2008 and April 2014 in a comprehensive cancer *** chemotherapy(CT)was administered by combining oxaliplatin with capecitabine(XELOX regimen).Disease-free survival(DFS)and overall survival(OS)rates of patients with or without ACT were ***:Eighty-three(79.0%)patients received ACT and 22(21.0%)did *** a median follow-up of 49 months,the ACT group had a significantly higher 3-year DFS rate(92.8 vs 86.4%,p=0.029)and 3-year OS rate(95.1 vs 86.1%,p=0.026)than the non-ACT *** multivariable analyses,the presence of ACT was an independent prognostic factor for DFS(hazard ratio[HR]:0.271;95%confidence interval(CI):0.080–0.916;p=0.036)but not for *** benefit was more obvious in patients younger than 60 years via subgroup analysis(adjusted HR:0.106;95%CI:0.019–0.606;p=0.012).Conclusions:Oxaliplatin-containing ACT may confer survival benefits to patients with pCR,particularly younger ***,the routine use of ACT in patients with pCR needs further validation.

关键词： Adjuvant chemotherapy rectal cancer pre-operative chemoradiotherapy pathological complete response survival

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Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial

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Chinese Journal of Cancer 2015年第9期34卷 26-35页

作者： Wen-Hua Fan Fu-Long Wang Zhen-Hai Lu zhi-zhong pan Li-Ren Li Yuan-Hong Gao Gong Chen Xiao-Jun Wu Pei-Rong Ding zhi-Fan Zeng De-Sen Wan State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer Center Department of Colorectal Surgery Sun Yat-sen University Cancer Center Department of Radiation Oncology Sun Yat-sen University Cancer Center

Introduction: Multimodality therapy, including preoperative chemoradiotherapy(CRT) and total mesorectal excision(TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy(CCRT) involving XELOX regimen(oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal ***: We randomly assigned patients to the TME group(TME without preoperative CCRT) or CCRT + TME group(TME with preoperative CCRT). The primary endpoint was disease-free survival(DFS); the secondary endpoints were overall survival(OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 ***: A total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 %(P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 %(P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT +TME groups were 71.3 % and 70.0 %(P = 0.849), respectively. In the TME group, 16(17.0 %) patients were proven to have p TNM stage I disease after surgery. In the CCRT + TME group, 32(35.6 %) patients achieved a pathologic complete response(p CR).Conclusions: Preliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high p CR rate. Newer technique

关键词： Rectal cancer, Total mesorectal excision, Chemoradiotherapy, Oxaliplatin, Capecitabine

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Programmed death-ligand 1 expression in the tumour stroma of colorectal liver oligometastases and its association with prognosis after liver resection

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Gastroenterology Report 2021年第5期9卷 443-450,I0002页

作者： Jian-Hong Peng Yi Tai Yi-Xin Zhao Bao-Jia Luo Qing-Jian Ou zhi-zhong pan Lin Zhang Zhen-Hai Lu Department of Colorectal Surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine GuangzhouGuangdongP.R.China Department of Clinical Laboratory Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China

Background The clinical value of programmed death-ligand 1(PD-L1)expression in colorectal liver oligometastases(CLOs)remains *** study aimed to detect PD-L1 in the microenvironment of CLOs and determine its association with patient *** We collected 126 liver-resection specimens from CLO patients who underwent curative liver resection between June 1999 and December ***(IHC)was performed to assess PD-L1 expression in paraffinembedded *** survival(OS)and recurrence-free survival(RFS)were analysed using the Kaplan–Meier method and log-rank *** PD-L1 was mainly expressed in the stroma of liver *** with high PD-L1 expression had a higher proportion of clinical-risk scores(CRSs)of 2–4(67.7%vs 40.4%;P=0.004).With a median 58-month follow-up,patients with high PD-L1 expression had a significantly lower 3-year OS rate(65.5%vs 92.7%;P=0.001)and 3-year RFS rate(34.7%vs 83.8%;P<0.001)than patients with low PD-L1 *** Cox analysis demonstrated that high PD-L1 expression(hazard ratio[HR]=3.581;95%confidence interval[CI]2.301–9.972;P=0.015),CRS 2–4(HR=6.960;95%CI 1.135–42.689;P=0.036)and increased preoperative CA19-9(HR=2.843;95%CI 1.229–6.576;P=0.015)were independent risk factors for *** PD-L1 expression(HR=4.815;95%CI 2.139–10.837;P<0.001)and lymph-node metastasis(HR=2.115;95%CI 1.041–4.297;P=0.038)were independent risk factors for *** This study found that PD-L1 was commonly expressed in the tumour stroma of CLOs and high PD-L1 expression was associated with poor prognosis.

关键词： PD-L1 colorectal liver oligometastases expression prognosis

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Germline mutational profile of Chinese patients under 70 years old with colorectal cancer

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Cancer Communications 2020年第11期40卷 620-632页

作者： Teng-Jia Jiang Fang Wang Ying-Nan Wang Jia-Jia Hu Pei-Rong Ding Jun-zhong Lin zhi-zhong pan Gong Chen Jian-Yong Shao Rui-hua Xu Qi Zhao Feng Wang State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineDepartment of OncologySun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Molecular Diagnosis Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Experimental Research Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Colorectal Surgery Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China

Background:Inherited susceptibility accounts for nearly one-third of colorectal cancer(CRC)predispositions and has an 80%-100%lifetime risk of this ***,there are few data about germline mutations of hereditary CRC-related genes in Chinese patients with *** study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC,differences between Chinese and Western patients,and the phenotypegenotype ***:We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing.A series of bioinformatic analyses,as well as statistical comparisons,were ***:We found that 77 patients(14.6%)harbored functional variants of the 12 *** mutation frequencies of the top 5 mutated genes were 6.5%for MutL homolog 1(MLH1),5.1%for MutS homolog 2(MSH2),1.0%for MSH6,0.8%for PMS1 homolog 2(PMS2),and 0.8%for APC regulator of the WNT signaling pathway(APC).Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair(MMR)genes as compared with those in Western *** in MLH1,MSH2,and MSH6 were found to be mutually *** with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer(MLH1:20.6%vs.8.7%;MSH2:25.9%vs.8.6%)and family history of cancer than those without these mutations(MLH1:73.5%vs.48.4%;MSH2:70.4%vs.48.9%),and the lesions were more prone to occur on the right side of the colon than on the left side(MLH1:73.5%vs.29.3%;MSH2:56.0%vs.31.0%).The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations(70.6%vs.50.7%),and the rate of polyps was higher in patients withAPC mutations than in those with wild-type APC(75.0%vs.17.4%).Conclusion:These results provide a full-scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi-ge

关键词： colorectal cancer genetic testing germline mutation hereditary CRC syndromes

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Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer

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Chinese Journal of Cancer 2016年第10期35卷 535-545页

作者： Bo Qiu Pei-Rong Ding Ling Cai Wei-Wei Xiao zhi-Fan Zeng Gong Chen Zhen-Hai Lu Li-Ren Li Xiao-Jun Wu Rene-Olivier Mirimanoff zhi-zhong pan Rui-Hua Xu Yuan-Hong Gao State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat?sen University Cancer Center Department of Radiation Oncology Sun Yat?sen University Cancer Center Department of Colorectal Surgery Sun Yat?sen University Cancer Center Department of Radiation Oncology Centre Hospitalier Universitaire Vaudois Department of Medical Oncology Sun Yat?sen University Cancer Center

Background: Complete resection of locally advanced sigmoid colon cancer(LASCC) is sometimes difficult. Patients with LASCC have a dismal prognosis and poor quality of life, which has encouraged the evaluation of alternative multimodality treatments. This prospective study aimed to assess the feasibility and efficacy of neoadjuvant chemora?diotherapy(neo CRT) followed by surgery as treatment of selected patients with unresectable ***: We studied the patients with unresectable LASCC who received neo CRT followed by surgery between October 2010 and December 2012. The neoadjuvant regimen consisted of external?beam radiotherapy to 50 Gy and capecitabine?based chemotherapy every 3 weeks. Surgery was scheduled 6–8 weeks after ***: Twenty?one patients were included in this study. The median follow?up was 42 months(range, 17–57 months). All patients completed neo CRT and surgery. Resection with microscopically negative margins(R0 resection) was achieved in 20 patients(95.2%). Pathologic complete response was observed in 8 patients(38.1%). Multivisceral resection was necessary in only 7 patients(33.3%). Two patients(9.5%) experienced grade 2 postopera?tive complications. No patients died within 30 days after surgery. For 18 patients with pathologic M0(yp M0) disease, the cumulative probability of 3?year local recurrence?free survival, disease?free survival and overall survival was 100.0%, 88.9% and 100.0%, respectively. For all 21 patients, the cumulative probability of 3?year overall survival was 95.2% and bladder function was well ***: For patients with unresectable LASCC, preoperative chemoradiotherapy and surgery can be performed safely and may result in an increased survival rate.

关键词：手术切除结肠癌患者化疗晚期前放 CRT 生存率

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Neoadjuvant oxaliplatin and capecitabine combined with bevacizumab plus radiotherapy for locally advanced rectal cancer: results of a single-institute phase II study

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Cancer Communications 2018年第1期38卷 263-271页

作者： Xin Yu Qiao-xuan Wang Wei-wei Xiao Hui Chang zhi-fan Zeng Zhen-hai Lu Xiao-jun Wu Gong Chen zhi-zhong pan De-sen Wan Pei-rong Ding Yuan-hong Gao Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuang-zhouP.R.China Department of Radiation Oncology Sun Yat-sen University Cancer Center651 Dongfeng Rd EastGuangzhou 510060P.R.China Department of Colorectal Surgery Sun Yat-sen University Cancer Center651 Dongfeng Rd EastGuangzhou 510060P.R.China

Background:Neoadjuvant chemoradiotherapy followed by surgery is recommended as the standard of care for locally advanced rectal cancer,reducing local recurrence but not distant *** systemic therapy is warranted to reduce the risk of distant *** present study aimed to evaluate the safety and efficacy of neo-adjuvant oxaliplatin and capecitabine(XELOX)combined with bevacizumab plus radiotherapy for locally advanced rectal ***:Patients with stages II to III rectal cancer received one cycle of induction chemotherapy and concurrent chemoradiotherapy with XELOX plus *** was performed 6-8 weeks after completion of radiotherapy,and postoperative chemotherapy with three cycles of XELOX and two cycles of capecitabine were *** primary endpoints were pathologic complete response(pCR)rate and safety,and the secondary endpoints were 3-year overall survival and progression-free ***:Forty-five patients were enrolled between February 2013 and April *** completed the neoadjuvant *** patients(15.6%)refused subsequent surgical therapy for personal reasons,and the other 38 patients received radical resection,with a sphincter preservation rate of 84.2%and a pCR rate of 39.5%.Toxicity was acceptable,with grades 3-4 hematological toxicity and diarrhea observed in six and two patients,*** of anastomotic leak that required surgical intervention was 13.3%.After a median follow-up period of 37 months,five patients developed disease progression and two died of *** 3-year overall survival rate and 3-year progres-sion-free survival rate were 95.3%and 88.6%,***:The addition of bevacizumab to neoadjuvant chemoradiotherapy resulted in a satisfying pCR rate and 3-year survival,but also may increase the risk of anastomotic leak,thus this regimen is not suitable to be considered for regular recommendation for locally advanced rectal cancer.

关键词： Bevacizumab Neoadjuvant chemoradiotherapy Locally advanced rectal cancer Safety Efficacy

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The loss-of-function mutations and down-regulated expression of ASB3 gene promote the growth and metastasis of colorectal cancer cells

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Chinese Journal of Cancer 2017年第1期36卷 11-25页

作者： Wu-Ying Du Zhen-Hai Lu Wen Ye Xiang Fu Yi Zhou Chun-Mei Kuang Jiang-Xue Wu zhi-zhong pan Shuai Chen Ran-Yi Liu Wen-Lin Huang State Key Laboratory of Oncology in South China Collaborative Innovation Center of Cancer Medicine Sun Yat-sen University Cancer Center Department of Radiation Oncology University of Arkansas for Medical Sciences Department of Oncology The First Affiliated Hospital Sun Yat-sen University Department of Radio-chemotherapy Shangrao People’s Hospital Guangdong Provincial Key Laboratory of Tumor-targeted Drug and Guangzhou Enterprise Key Laboratory of Gene Medicine Guangzhou Doublle Bioproducts Co. Ltd.

Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor ***: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and ***: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.

关键词： Ankyrin repeat and SOCS box protein 3(ASB3) Colorectal cancer Epithelial-mesenchymal transition Cell proliferation Tumor metastasis

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