title: Upregulation of autophagy-related gene-5 (ATG-5) is associated with chemoresistance in human gastric cancer.
abstract: Autophagy-related gene-5 (ATG-5) is one of the key regulators of autophagic cell death. It has been widely regarded as a protective molecular mechanism for tumor cells during the course of chemotherapy. In the present study, we investigated the expression pattern of ATG-5 and multidrug resistance-associated protein-1 (MRP-1) in 135 gastric cancers (GC) patients who were treated with epirubicin, cisplatin and 5-FU adjuvant chemotherapy (ECF) following surgical resection and explored their potential clinical significance. We found that both ATG-5 (77.78%) and MRP-1 (79.26%) were highly expressed in GC patients. ATG-5 expression was significantly associated with depth of wall invasion, TNM stages and distant metastasis of GC (P<0.05), whereas MRP-1 expression was significantly linked with tumor size, depth of wall invasion, lymph node metastasis, TNM stages and differentiation status (P<0.05). ATG-5 expression was positively correlated with MRP-1 (rp = 0.616, P<0.01). Increased expression of ATG-5 and MPR-1 was significantly correlated with poor overall survival (OS; P<0.01) and disease free survival (DFS; P<0.01) of our GC cohort. Furthermore, we demonstrated that ATG-5 was involved in drug resistant of GC cells, which was mainly through regulating autophagy. Our data suggest that upregulated expression of ATG-5, an important molecular feature of protective autophagy, is associated with chemoresistance in GC. Expression of ATG-5 and MRP-1 may be independent prognostic markers for GC treatment.
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000071187:Autophagy-Related Protein 5; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C502778:ATG5 protein, human; C421109:multidrug resistance-associated protein 1