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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01183

Aberrant Scinderin Expression Correlates with Liver Metastasis and Poor Prognosis in Colorectal Cancer

Qi Lin1,  Jun Li1, Dexiang Zhu1,  Zhengchuan Niu1, Xiangou Pan1, Pingping Xu1, Meilin Ji1,  Ye Wei1 and  Jianmin Xu1*
  • 1Zhongshan Hospital, Fudan University, China

Many genes and mutations have been reported for colorectal cancer (CRC), however, very few have been associated with colorectal cancer liver metastasis (CRLM). We performed gene expression profiling experiments to identify genetic markers for CRLM and elucidate the molecular mechanisms. Microarray experiments were performed on CRC primary tumor samples with or without liver metastasis using the Affymetrix U133 plus 2.0 Gene Chip Array. A new identified gene-scinderin (SCIN) was over expressed with synchronous liver metastasis at both the RNA level evaluated with quantitative real-time PCR and protein level evaluated with immunohistochemistry, and also with short overall survival analyzed with Kaplan-Meier method. With multivariate analysis indicated that SCIN served as an independent poor prognostic predictor for CRC patients. Disease-free survival was also significantly lower in SCIN overexpressing CRC patients with metachronous liver metastasis. In addition, SCIN knockdown significantly reduced cell proliferation, induced cell cycle arrest and promoted the expression of some cell cycle apoptosis-related protein. Moreover, the DIAPH1, STAT3, CDK2, CDK4 and EGFR levels were down-regulated, whereas CDKN2B and COL4A1 were up-regulated in DLD-1-shSCIN cells by Microarray analysis compared with DLD-1 shCon cells. These findings revealed SCIN may serve as an important predictor of CRLM and poor outcome for CRC patients. SCIN may be a potential therapeutic target in human CRC. However, translation of its roles into clinical practice will require further investigation and additional experimental validation.

Keywords: Scinderin, colorectal cancer, liver metastasis, Genome-Wide Association Study, prognosis

Received: 25 Jan 2019; Accepted: 13 Sep 2019.

Copyright: © 2019 Lin, Li, Zhu, Niu, Pan, Xu, Ji, Wei and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Jianmin Xu, Zhongshan Hospital, Fudan University, Shanghai, Shanghai Municipality, China, xujmin@aliyun.com