Comprehensive Transcriptomic Analysis Reveals Prognostic Value of an EMT-Related Gene Signature in Colorectal Cancer

Shaobo Mo; Weixing Dai; Zheng Zhou; Ruiqi Gu; Yaqi Li; Wenqiang Xiang; Lingyu Han; Long Zhang; Renjie Wang; Guoxiang Cai; Sanjun Cai; Lu Gan; Qingguo Li

doi:10.3389/fcell.2021.681431

Comprehensive Transcriptomic Analysis Reveals Prognostic Value of an EMT-Related Gene Signature in Colorectal Cancer

Front Cell Dev Biol. 2021 Jun 15:9:681431. doi: 10.3389/fcell.2021.681431. eCollection 2021.

Authors

Shaobo Mo^{1

2}, Weixing Dai^{1

2}, Zheng Zhou^{1

2}, Ruiqi Gu^{1

2}, Yaqi Li^{1

2}, Wenqiang Xiang^{1

2}, Lingyu Han^{1

2}, Long Zhang^{1

3}, Renjie Wang^{1

2}, Guoxiang Cai^{1

2}, Sanjun Cai^{1

2

3}, Lu Gan^{4

5

6}, Qingguo Li^{1

2}

Affiliations

¹ Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
⁴ Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
⁵ Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
⁶ Center of Evidence-Based Medicine, Fudan University, Shanghai, China.

Abstract

Lymph node metastasis (LNM) is closely related to the postoperative recurrence of colorectal cancer (CRC), and greatly affects patient survival. Conducting Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA), we found that the epithelial-mesenchymal transition (EMT) signaling pathway is the signaling pathway most relevant to the process of LNM. An EMT-related gene signature was identified from a discovery dataset obtained 489 patients using LIMMA and LASSO Cox methods. Six external independent dataset analyses including a total of 1,045 CRC patients and stratification analysis showed that EMT-related gene signature could sort out those high- and low-risk CRC patients accurately. Functional analysis and loss-of-function exploration in vitro and in vivo indicated that the EMT-related-signature-associated coding genes might play functional roles in the sophisticated regulation of CRC proliferation and metastasis. Prognostic nomograms integrating the EMT-related gene signature and clinicopathological risk factors were constructed for use as numerical prediction tools to assess clinical prognosis and clinical decision-makings. The comprehensive transcriptomic analysis in this article highlights the prognostic value of an EMT-related gene signature for postoperative disease recurrence in CRC patients and reveals a potential prognostic and therapeutic biomarker for CRC.

Keywords: EMT; colorectal cancer; nomogram; prognosis; signature.