title: Expression of Ras-related protein 25 predicts chemotherapy resistance and prognosis in advanced non-small cell lung cancer.
abstract: Ras-related protein 25 (Rab25) is involved in many human malignancies. However, its role in chemotherapy response and prognosis in advanced non-small cell lung cancer (NSCLC) remains unknown. Therefore, we investigated the relationship between Rab25 and chemotherapy sensitivity and prognosis in NSCLC. Rab25 expression was assessed using immunohistochemistry in 324 advanced NSCLC patients. Its correlations with clinical features were analyzed. Sensitivity to cisplatin (DDP) was compared between DDP-sensitive A549 and DDP-resistant A549/DDP cells. Furthermore, small interfering RNA (siRNA) targeting Rab25 was used for in vitro experiments. Patients with positive Rab25 expression had a significantly lower chemotherapy response rate (P = 0.004) and poorer overall survival (OS, P = 0.0012) than those with negative Rab25 expression. Multivariate analysis indicated that Rab25 expression was an independent prognostic factor for OS (P = 0.016). Moreover, Rab25 expression was significantly higher in A549/DDP cells than in A549 cells. Knockdown of Rab25 by siRNA suppressed cell migration and invasion. Cisplatin resistance in A549/DDP cells was also partially reversed by Rab25 silencing. Rab25 expression is a potential prognostic index for advanced NSCLC patients and its inhibition may improve chemosensitization in NSCLC treatment.
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Ma
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: J T
authors.initials: JT
authors.lastname: Guo
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Liang
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C509763:Rab25 protein, human; D020691:rab GTP-Binding Proteins; D002945:Cisplatin