A Gene Expression Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 as an Oncogenic Gene That Promotes CRC Cells Migration by RhoA/ROCK1 Signaling Pathway

Abstract

Background: Colorectal cancer (CRC) experiencing early relapse consistently exhibited poor survival. However, an effective method for the diagnosis and prognosis of CRC postoperative relapse has not been developed. Methods: WGCNA analysis, RRA analysis and TNM staging difference analysis were conducted to screen the key genes in CRC dataset. The COX/LASSO regression model was used to construct CRC recurrence model in GSE33113. GSE39582 and TCGA database were used to further validate the diagnostic value of the model. The CCK8, Transwell and wound-healing assays were used to detect the biological function of LEMD1 in CRC cells. Rho GTPases pulldown experiment were conducted to investigate the mechanism by which LEMD1 promotes the activity of RhoA. Findings: a CRC relapse model composing of LEMD1, SERPINE1, and SIAE was constructed based on multiple datasets. The model was positively correlated with TNM stage and could be independent prognostic factor. Further in vitro experiments proved that LEMD1 could regulate CRC cell proliferation, migration, invasion and promote EMT transition. Specifically, we determined that LEMD1 promotes CRC cell migration through the RhoA/ROCK signaling pathway. Interpretation: We developed a CRC recurrence model which may be used to predict CRC recurrence early; LEMD1 may serve as a potential strategy for prevention and treatment in human CRC. Funding: This study was supported by Jiangsu Provincial Key Research Development Program (Grant/Award Number: BE2016794 and BE2016795). Declaration of Interest: The authors disclose no conflicts of interest. Ethical Approval: The study was carried out in accordance with the principles of the Helsinki Declaration and was approved by the Ethics Boards of Jiangsu Cancer Hospital.