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

• Published in: Molecular medicine reports Vol. 14; no. 3; pp. 2541 - 2547
• Main Authors: Ma, Ying-Yu, Wang, Xiao-Jun, Han, Yong, Li, Gang, Wang, Hui-Ju, Wang, Shi-Bing, Chen, Xiao-Yi, Liu, Fan-Long, He, Xiang-Lei, Tong, Xiang-Min, Mou, Xiao-Zhou
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.09.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Adenoviridae - physiology; adenovirus-mediated gene therapy; Adenoviruses; Adult; Aged; Aged, 80 and over; Alcohol; Biomarkers; CAR; Carcinogenesis; Care and treatment; Cell Line, Tumor; Cell Membrane - metabolism; Chinese Han population; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Colorectal Neoplasms - therapy; Coxsackie and Adenovirus Receptor-Like Membrane Protein - genetics; Coxsackie and Adenovirus Receptor-Like Membrane Protein - metabolism; Development and progression; DNA microarrays; Female; Gene Expression; Gene therapy; Genetic aspects; Genetic Therapy; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Humans; Immunohistochemistry; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Kaplan-Meier Estimate; Liver; Lymph nodes; Lymphatic system; Male; Medical prognosis; Metastases; Metastasis; Methods; Middle Aged; Mortality; Mucosa; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Oncolysis; Patient outcomes; Prognosis; Properties; Protein expression; Transduction, Genetic; Tumor Burden; Tumor suppressor genes; Viruses; United States > US; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2016.5536

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.