title: RAD51B as a potential biomarker for early detection and poor prognostic evaluation contributes to tumorigenesis of gastric cancer.
abstract: Gastric cancer (GC) is a common and deadly disease worldwide. Outcomes of patients are poor largely due to chemoresistance or recurrence. Thus, identifying novel biomarkers to predict response to therapy and/or prognosis are urgently needed. RAD51B, a key player in DNA repair/recombination, has the potential to be a candidate oncogene and biomarker for cancer diagnosis and prognosis. However, its relationship with GC remains unclear. To evaluate clinicopathological and prognostic significance of RAD51B in GC, we examined messenger RNA (mRNA) and protein expression via quantitative real-time polymerase chain reaction (qRT-PCR) from 69 and tissue microarray from 144 GC patients, respectively. Our results showed that RAD51B mRNA expression was significantly up-regulated in tumors compared to that of matched noncancerous tissues (P < 0.001). In parallel, RAD51B protein showed a mainly nucleus-staining pattern, and the positive rate in tumors and stomach atypical hyperplasia was significantly higher than that in matched noncancerous tissues (P = 0.015). Moreover, high level of RAD51B protein was correlated with advanced stage (P = 0.009), aggressive differentiation (P = 0.022), and lymph node metastasis (P = 0.001). Further, Kaplan-Meier analysis indicated that patients with high level of RAD51B expression exhibited worse overall survival compared to patients with low level (P = 0.040). A multivariate Cox regression analysis suggested that RAD51B may be an independent prognostic factor for GC patients in Chinese population (P = 0.004). Additionally, functional studies indicated that over-expression of RAD51B promoted cell proliferation, aneuploidy, and drug resistance, while RAD51B knockdown led to G1 arrest and sensitized cells to 5-fluorouracil (5-FU). In conclusion, RAD51B may act as an oncogene during GC progression, and its hyper-expression may be a potential biomarker for early detection and poor prognosis of GC.
authors.affiliation: Beijing New Oriental Foreign Language School at Yangzhou, Yangzhou, Jiangsu, 225006, China.
authors.forename: Yikun
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Tumor Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi, 030001, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi, 030001, People's Republic of China. xyf609@sohu.com.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Endoscopy, Shanxi Cancer Hospital, Taiyuan, Shanxi, 030001, China. chenxing8181@163.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D055088:Early Detection of Cancer; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C413002:RAD51B protein, human; D034741:RNA, Small Interfering; C491395:MKNK1 protein, human; D017346:Protein Serine-Threonine Kinases; D005472:Fluorouracil
keywords: Drug resistance; Gastric cancer; Genomic instability; Oncogene; Prognosis; RAD51B