ORMDL1 is upregulated and associated with favorable outcomes in colorectal cancer

Qian Wang; Wanjun Liu; Si Chen; Qianxin Luo; Yichen Li; Shaoyong Peng; Huaiming Wang; Xiaoxia Liu; Daici Chen

doi:10.1016/j.tranon.2021.101171

ORMDL1 is upregulated and associated with favorable outcomes in colorectal cancer

Transl Oncol. 2021 Oct;14(10):101171. doi: 10.1016/j.tranon.2021.101171. Epub 2021 Jul 6.

Authors

Qian Wang¹, Wanjun Liu¹, Si Chen¹, Qianxin Luo², Yichen Li¹, Shaoyong Peng¹, Huaiming Wang³, Xiaoxia Liu¹, Daici Chen⁴

Affiliations

¹ Guangdong Institute of Gastroenterology, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China.
² Guangdong Institute of Gastroenterology, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Department of Intensive Care Unit, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China.
³ Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China.
⁴ Guangdong Institute of Gastroenterology, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China; Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou, Guangdong 510655, China. Electronic address: chendc3@mail.sysu.edu.cn.

Abstract

Background: The ORMDL1 gene is known as a crucial negative regulator of sphingolipid biogenesis. However, the ORMDL1 gene has rarely been studied in a tumor-related context. Therefore, its prognostic value and functional significance in colorectal cancer (CRC) remain to be explored.

Methods: TCGA CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the ORMDL1 expression level. The association between ORMDL1 expression and various clinical characteristics was analyzed by chi-square tests. The overall survival (OS) of CRC patients was analyzed by Kaplan-Meier analysis. In vitro and in vivo cell-based assays were performed to explore the role of ORMDL1 in cell proliferation, invasion and migration. Transcriptional changes in cells with either ORMDL1 knockdown or overexpression were compared and analyzed.

Results: ORMDL1 was upregulated in CRC tissues in both the TCGA and our cohort. Interestingly, its expression was significantly lower in patients with metastasis than in patients without metastasis, and the high expression group had longer OS than the low expression group. Knockdown of ORMDL1 expression can promote proliferation, colony formation and invasion, while attenuating migration in CRC cell lines. In contrast, forced overexpression of ORMDL1 reduced cell proliferation, colony formation and invasion, while enhancing cell migration. Stable knockdown of ORMDL1 can promote cancer cell proliferation in vivo to some extent. Finally, Rho GTPase activity was influenced by ORMDL1, and the expression of ORMDL1 was enhanced by DTT treatment.

Conclusion: ORMDL1 is upregulated and may serve as a biomarker to predict favourable outcomes in colorectal cancer.

Keywords: Colorectal cancer; ORMDL1; Prognosis.