Prognostic Value and Correlation With Tumor Immune Infiltration of a Novel Metabolism-Related Gene Signature in Pancreatic Cancer

Hui Chen; Fuqiang Zu; Taofei Zeng; Ziang Chen; Jinhong Wei; Peng Liu; Zeyu Li; Lei Zhou; Huaitao Wang; Hao Tan; Xiaodong Tan

doi:10.3389/fonc.2021.757791

Prognostic Value and Correlation With Tumor Immune Infiltration of a Novel Metabolism-Related Gene Signature in Pancreatic Cancer

Front Oncol. 2022 Jan 19:11:757791. doi: 10.3389/fonc.2021.757791. eCollection 2021.

Authors

Hui Chen¹, Fuqiang Zu¹, Taofei Zeng², Ziang Chen³, Jinhong Wei⁴, Peng Liu¹, Zeyu Li¹, Lei Zhou¹, Huaitao Wang¹, Hao Tan⁵, Xiaodong Tan¹

Affiliations

¹ General Surgery, Department of Pancreatic and Thyroid Ward, Shengjing Hospital of China Medical University, Shenyang, China.
² General Surgery, Department of Hepatobiliary and Splenic Ward, Shengjing Hospital of China Medical University, Shenyang, China.
³ Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
⁴ School of Basic Medical Sciences, Southwest Medical University, Luzhou, China.
⁵ General Surgery, Department of Pancreatic and Endocrine Ward, Shengjing Hospital of China Medical University, Shenyang, China.

Abstract

Background: Energy metabolism has been considered as one of the novel features of neoplasms. This study aimed to establish the prognostic signature for pancreatic cancer (PC) based on metabolism-related genes (MRGs).

Methods: We obtained MRGs from the Molecular Signatures Database (MSigDB) and gene sequence data in the Cancer Genome Atlas (TCGA) databases. Then, differentially expressed MRGs (DE-MRGs) were identified utilizing the R software. We built the prognostic model via multivariate Cox regression. Moreover, external validation of the prognostic signature was also performed. Nomogram was created to predict the overall survival (OS). Next, this study analyzed the prognostic value, clinical relationship, and metabolism-related signaling pathways of the prognostic signature. The role in tumor infiltration was further evaluated. Eventually, the expression level of the three MRGs along with the function of NT5E was validated.

Results: Twenty-two MRGs were chosen, eight of which were identified to be most significantly correlated with the prognosis of PC. Meanwhile, a 3-MRG prognostic signature was established, and we verified this prognostic model in two separate external cohorts. What is more, the nomogram was used to predict 1-/2-/3-year OS of PC patients. In addition, the immune cell infiltration and expression of immune checkpoint were significantly influenced by the risk score. Finally, three MRGs were highly expressed in PC cell lines, and NT5E was associated with the proliferation and migration ability of PC.

Conclusion: To sum up, the study established and validated a 3-MRG prognostic signature for PC, and the signature could be utilized to predict the prognosis and assist the individualized clinical management of patients with PC.

Keywords: immunotherapy; metabolism-related genes; pancreatic cancer; prognostic signature; tumor immune microenvironment.