title: RBMS3 is a tumor suppressor gene that acts as a favorable prognostic marker in lung squamous cell carcinoma.
abstract: Recent research indicates that RBMS3 may act as a tumor suppressor gene (TSG) in nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). It has been reported that RBMS3 directly binds to the promoter region of c-Myc in ESCC and that β-catenin from both whole cell extracts and nuclear fractionation was significantly downregulated in RBMS3-transfected NPC cells compared to control cells. The aim of this study was to evaluate the clinical significance of the RBMS3 gene expression in relation to the expression of Wnt pathway components in patients with lung squamous cell carcinoma (LSCC). RBMS3, c-Myc and cytoplasmic β-catenin were detected in 39.76, 56.63 and 89.16 % of 83 LSCC samples by immunohistochemistry, respectively, in 83 primary LSCC samples. Semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting demonstrated decreased RBMS3 mRNA and expression in 33.33 % (10/30) and 36.67 % (11/30) tumor tissues, respectively. Statistical correlation analysis showed RBMS3 to be negatively correlated with c-Myc (r = -0.384, p < 0.001) and not correlated with cytoplasmic β-catenin in the LSCC samples. Multivariate Cox proportional hazards model analysis showed that the combined marker RBMS3/c-Myc was an independent prognostic indicator of overall survival (p = 0.001; HR 3.470; IC 95 %, 1.652-7.290), and c-Myc was a prognostic indicator of disease-free survival (p < 0.001; HR 3.182; IC 95 %, 1.961-8.920). RBMS3 is a novel TSG in LSCC, and its downregulation facilitates development and progression of LSCC. Therefore, it is suggested that Rbms3 as a tumor marker may play an important role in diagnosis of LSCC.
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Liang
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Meng
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Guodong
authors.initials: G
authors.lastname: Yao
authors.forename: Letian
authors.initials: L
authors.lastname: Wang
authors.forename: Songbin
authors.initials: S
authors.lastname: Fu
authors.forename: Dandan
authors.initials: D
authors.lastname: Tong
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C405932:RBMS3 protein, human; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D051176:beta Catenin