title: ITGA2B and ITGA8 are predictive of prognosis in clear cell renal cell carcinoma patients.
abstract: Integrins play an important role in cancer growth and metastasis. This study aimed at determining the predictive ability of integrins and associated genes identified through molecular network in clear cell renal cell carcinoma. A total of 525 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression profile of integrins and related genes were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, gender, tumor size, tumor node metastasis (TNM), tumor grade, stage, laterality, and overall survival were collected. Cox proportional hazards regression model as well as Kaplan-Meier curve were used to assess the relative factors. Genes of integrin family that showed certain correlations with overall survival (OS) were further validated in the Fudan University Shanghai Cancer Center (FUSCC) cohort. In the TCGA cohort, after Cox proportional hazards analysis, ITGA2B (hazards ratio (HR) = 1.232, 95 % CI 1.097 to 1.383) and ITGA8 (HR = 0.804, 95 % CI 0.696 to 0.930) were shown predictive of ccRCC prognosis. Low ITGA8 expression was associated with poor prognosis for OS (log-rank test, p < 0.0001), while high level of ITGA2B expression was correlated with poor prognosis for OS (log-rank test, p < 0.0001). This finding was validated in FUSCC cohort (log-rank test, all p < 0.05). As a result, low ITGA8 expression was associated with poor prognosis for OS (log-rank test, p = 0.0053), while high level of ITGA2B expression was correlated with poor prognosis for OS (log-rank test, p < 0.0001). Plus, low ITGA8 expression was associated with poor prognosis for disease-free survival (DFS) in the TCGA cohort (log-rank test, p < 0.0001). In the gene cluster network analysis, GIT1 and SHC1 associated with ITGA2B and ITGA8 were identified as independent predictive factors of overall survival of ccRCC. ITGA2B, ITGA8, GIT1, and SHC1 were identified as independent prognostic factors of overall survival of ccRCC. This method may act as a tool to reveal more prognostic-associated genes in ccRCC.
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270, Dong'an Road, Shanghai, 200032, People's Republic of China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270, Dong'an Road, Shanghai, 200032, People's Republic of China.
authors.forename: Fangning
authors.initials: F
authors.lastname: Wan
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270, Dong'an Road, Shanghai, 200032, People's Republic of China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270, Dong'an Road, Shanghai, 200032, People's Republic of China.
authors.forename: Guohai
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China. dwyeli@163.com.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270, Dong'an Road, Shanghai, 200032, People's Republic of China. dwyeli@163.com.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Ye
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism*; D039421:Integrin alpha2 / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: C056564:ITGA2B protein, human; C579157:ITGA8 protein, human; D039001:Integrin alpha Chains; D039421:Integrin alpha2; D016023:Integrins
keywords: Clear cell renal cell carcinoma; GIT1; ITGA2B; ITGA8; Integrin; Prognosis; SHC1