Abstract 2340: Integrin subunit alpha 5: Potential prognostic biomarker in lung adenocarcinoma

Abstract

Abstract Identifying patients at high risk for recurrence in resected non-small cell lung cancer (NSCLC) is the key to choosing patients who can benefit from postoperative adjuvant therapy. However, the criteria to stratify patients to receive postoperative adjuvant therapy are still clinicopathologic factor-oriented, such as differentiation, tumor size, the presence of pleural involvement and vascular invasion and so on. Even using adjuvant treatment under these criteria, 5-year survival rate is around 60% even in early-stage disease. Here, we extracted potential candidate genes for stratifying resected NSCLC patients according to correlation with their survival using public big data and validated the prognostic role of the extracted candidate gene in tumor samples of patients' cohort with resected NSCLC. Under hypothesis “X affects Y” (X: regulatory gene, Y: events related gene), we extracted X and Y gene pairs in the RNA expression data of stage I-IIIA NSCLC in The Cancer Genomic Atlas using correlation analysis, Cox regression modeling, and Bonferroni correction. Extracted 20 Y genes related death events among 20,501 genes 576 lung adenocarcinoma include: BEST3, SLC25A42, C1orf210, TLE1, CD109, VEGFC, CXCL17, LASS4, DKK1, LDLRAD3, EPGN, NKX2-1, FJX1, PLEKHB1, FLNC, RGS20, FUT1, LASS4, TTGB1, KRT6C. Then, here are the 38 X genes significantly related to each Y genes: C11orf52, PPFIBP1, GGTLC1, ST3GAL5, CRB3, TGFBI, HOPX, STK32A, ERBB3, C16orf89, IRX5, TMPRSS2, PRR15L, PIGR, LMO3, ITGA5, RAB17, TMEM125, LPCAT1, SNAI2, RAB25, ABCA3, MBIP, TMEM125, B3GNT8, NAPSA ARNTL2, C16orf89, SCNN1B, ELK3, CDKL2, SFTA2, GPR115, CISH, SFTA3, LAMC2, ESYT3, SFTPB. Among these extracted X and Y gene pairs, we choose only ITGA5 (X) and VEGFC (Y) pair according to their known function of lymphangiogenesis and vasculogenesis during tumorigenesis process. We hypothesized that IGTA5, which is related to VEGFC, could be potential biomarker in resected NSCLC. In TCGA data, patients with low expression of ITGA5 showed better recurrence-free survival (RFS) than those with high ITGA5 (54.4 vs. 32.8 months; P-value <0.001). Then, using tissue microarray of 100 patients with surgically resected NSCLC, the expression level of ITGA5 and VEGFC was assessed by immunohistochemistry and analyzed correlated with survival outcome for validation. The expression level of ITGA5 was significantly correlated with that of VEGFC (P-value=0.004). RFS was longer in patients with low ITGA5 expression than in those with high ITGA5 expression (55.6 vs. 21.6 months; P= 0.020). According to our data, ITGA5 that affects VEGFC might one of the potential biomarkers of the resected lung adenocarcinoma relevant survival outcome. Furthermore, the immunohistochemistry of the larger number of cohort and functional experiment of the regulation of ITGA5 toward VEGFC in cell levels of NSCLC are ongoing. Citation Format: Ji Hyung Hong, Jeong-Hun Lee, Na Ra Yoon, Suk Hee Hong, Yoon Ho Ko. Integrin subunit alpha 5: Potential prognostic biomarker in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2340.