title: Loss of coxsackie and adenovirus receptor expression in human colorectal cancer: A potential impact on the efficacy of adenovirus-mediated gene therapy in Chinese Han population.
abstract: The coxsackie and adenovirus receptor (CAR) is considered a tumor suppressor and critical factor for the efficacy of therapeutic strategies that employ the adenovirus. However, data on CAR expression levels in colorectal cancer are conflicting and its clinical relevance remains to be elucidated. Immunohistochemistry was performed on tissue microarrays containing 251 pairs of colon cancer and adjacent normal tissue samples from Chinese Han patients to assess the expression levels of CAR. Compared with healthy mucosa, decreased CAR expression (40.6% vs. 95.6%; P<0.001) was observed in colorectal cancer samples. The CAR immunopositivity in tumor tissues was not significantly associated with gender, age, tumor size, differentiation, TNM stage, lymph node metastasis or distant metastasis in patients with colon cancer. However, expression of CAR is present in 83.3% of the tumor tissues from patient with colorectal liver metastasis, which was significantly higher than those without liver metastasis (39.6%; P=0.042). At the plasma membrane, CAR was observed in 29.5% normal mucosa samples, which was significantly higher than in colorectal cancer samples (4.0%; P<0.001). In addition, the survival analysis demonstrated that the expression level of CAR has no association with the prognosis of colorectal cancer. CAR expression was observed to be downregulated in colorectal cancer, and it exerts complex effects during colorectal carcinogenesis, potentially depending on the stage of the cancer development and progression. High CAR expression may promote liver metastasis. With regard to oncolytic therapy, CAR expression analysis should be performed prior to adenoviral oncolytic treatment to stratify Chinese Han patients for treatment.
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Ma
authors.affiliation: Department of Anus, Rectum and Colon Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Colorectal Department of Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Shi-Bing
authors.initials: SB
authors.lastname: Wang
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Department of Anus, Rectum and Colon Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Fan-Long
authors.initials: FL
authors.lastname: Liu
authors.affiliation: Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Xiang-Lei
authors.initials: XL
authors.lastname: He
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Xiang-Min
authors.initials: XM
authors.lastname: Tong
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Xiao-Zhou
authors.initials: XZ
authors.lastname: Mou
mesh_terms: D000256:Adenoviridae / Q000502:physiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D014161:Transduction, Genetic; D047368:Tumor Burden
chemical_list: D015415:Biomarkers; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein