Autophagy-related genes Raptor, Rictor, and Beclin1 expression and relationship with multidrug resistance in colorectal carcinoma

• Published in: Human pathology 2015-11, Vol.46 (11), p.1752-1759
• Main Authors: Shuhua, Wu, MD, Chenbo, Sun, MSc, Yangyang, Li, MSc, Xiangqian, Gao, MSc, Shuang, He, MSc, Tangyue, Li, MSc, Dong, Tian, MD
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Antigens; Apoptosis; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Autophagy; Beclin-1; Beclin1; Cancer; Cancer therapies; Carrier Proteins - genetics; Carrier Proteins - metabolism; Chemotherapy; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Deoxyribonucleic acid; Disease Progression; DNA; Drug Resistance, Multiple - genetics; Drugs; Female; Genes; Humans; Immunohistochemistry; Lymphatic Metastasis - genetics; Lymphatic Metastasis - pathology; Male; MDR; Medical prognosis; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Middle Aged; Pathology; Prognosis; Rapamycin-Insensitive Companion of mTOR Protein; Raptor; Regulatory-Associated Protein of mTOR; Rictor; Studies; Survival Rate; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2015.07.016

Summary This study aims to evaluate the relationship between the expressions of autophagy-related genes Raptor, Rictor, and Beclin1 and the expression of multidrug resistance ( MDR ) gene in colorectal cancer (CRC) patients. Immunohistochemistry and real-time polymerase chain reaction were used to detect the protein and messenger RNA expressions of mammalian target of rapamycin (mTOR), Raptor, Rictor, Beclin1, light chain 3 (LC3), and MDR-1 in 279 CRC specimens. Patients were followed up annually by telephone or at an outpatient clinic. Results revealed that the protein and messenger RNA expressions of Beclin1, LC3, mTOR, Raptor, Rictor, and MDR-1 in CRC are significantly higher than in adjacent tissues. LC3 expression in poorly differentiated CRC is higher than that in well-differentiated CRC, and the expression of mTOR, Raptor, Rictor, and LC3 in lymph node metastasis is higher than that obtained in the absence of lymph node metastasis. The expression of LC3 is positively correlated with those of Beclin1 and Rictor and negatively correlated with Raptor and mTOR in CRC. The expression of Raptor is negatively correlated with Rictor. The expression of MDR-1 is positively correlated with those of Beclin1, LC3, and Rictor and negatively correlated with Raptor and mTOR. Kaplan-Meier analysis revealed that the 5-year survival rate of patients without lymph node metastasis; positive expression of Rictor, Beclin1, and LC3; and negative expression of Raptor and mTOR were higher than those with these characteristics. To conclude, the expressions of Beclin1, Raptor, and Rictor are related to the development and progression of colorectal carcinoma and MDR. (Clinical trial registration number: 2014-009-01.)