Abstract
Abstract Colorectal cancer (CRC) is the main cause of cancer mortality worldwide. Its poor prognosis is mainly ascribed to high recurrence rates. Identifying novel prognostic biomarkers and therapeutic key points for management is crucial and important. To develop prognostic biomarkers that can discriminate CRC patients with high risk of postoperative recurrence, we conducted RNA-seq analysis using primary cancer tissues from 130 CRC patients with (n=58) or without (n=72) systemic recurrence. Among differentially expressed genes between with or without recurrence, we identified eleven candidate genes (AK2, BID, CDC25A, EIF4A2, HSPB1, ITGB1, MAP4K4, MMP12, PTGES3, RHOC, TERF21P) (P < 0.01). Then, the expression level of the best candidate gene was validated by quantitative real-time polymerase chain reaction (qRT-PCR) in the additional 79 CRC patients with (n=40) or without (n=39) systemic recurrence. Among these genes, qRT-PCR showed that AK2, EIF4A2, ITGB1 and RhoC were upregulated. To the relevance of their molecular function and biological process, Cell Counting Kit-8 assay, migration, invasion assay and gelatin zymograpy were performed after knockdown or overexpression of candidate genes in CRC cell lines. ITGB1 or RhoC stimulated colon cancer cell proliferation, promoted cell invasion and migration, whereas the opposite pattern was observed in ITGB1 or RhoC-overexpressing CRC cells. Western blotting experiments revealed that ITGB1 and RhoC overexpression downregulated E-cadherin and upregulated N-cadherin, Snail/Slug, Vimentin protein levels, whereas ITGB1 and RhoC knockdown had the opposite effects These results suggested that ITGB1 and RhoC promoted colon cancer cell proliferation, migration and invasion through EMT switch signaling pathway. Our results indicate that ITGB1 and RhoC may be biomarkers to predict recurrence and future therapeutic targets of CRC. Citation Format: Ye Jin Ha, Ka Hee Tak, Chan Wook Kim, Jong Ryul Lee, Dong-Hyung Cho, Yong Sung Kim, Seon-Kyu Kim, Jin Cheon Kim. High ITGB1 & RhoC expressions are indicators of recurrence in patients with primary colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-042.
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