DLC1 Is a Prognosis-Related Biomarker Correlated With Tumor Microenvironment Remodeling in Endometrial Carcinoma

Yalan Wu; Li-E Zheng; Shumin Chen; Chengyu Lv; Yuxiu Huang

doi:10.3389/fonc.2022.823018

DLC1 Is a Prognosis-Related Biomarker Correlated With Tumor Microenvironment Remodeling in Endometrial Carcinoma

Front Oncol. 2022 Feb 11:12:823018. doi: 10.3389/fonc.2022.823018. eCollection 2022.

Authors

Yalan Wu¹, Li-E Zheng¹, Shumin Chen¹, Chengyu Lv², Yuxiu Huang¹

Affiliations

¹ Department of Gynecology, The Affiliated First Hospital of Fujian Medical University, Fuzhou, China.
² Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Abstract

Background and aim: Deleted in liver cancer 1 (DLC1) is confirmed as a metastasis suppressor gene in endometrial carcinoma (EC). However, its functional mechanisms remain unclear. This study aimed to explore the relationship between DLC1 expression and EC.

Methods: The Cancer Genome Atlas database was used for evaluating the expression of DLC1 in pan-cancer. CIBERSORT was used to assess the relationship between DLC1 and tumor immune infiltration. We applied real-time quantitative polymerase chain reaction to determine the expression of DLC1 in EC and adjacent normal tissue samples. The targeting endogenous protein levels were assessed using the dataset from the cBioPortal database.

Results: DLC1 expression negatively correlated with the clinical characteristics (clinical stage, histologic grade) and positively correlated with the survival of patients with uterine corpus EC (UCEC). The gene set enrichment analysis displayed that the low-expression DLC1 group was enriched in metabolic pathways. Concomitantly, the high-expression DLC1 group was enriched in tumor immune-related activities. The CIBERSORT analysis showed that the number of resting memory CD4 T cells and resting mast cells positively correlated with DLC1 expression, while the number of macrophages M2 had a negative correlation, indicating that DLC1 played a key role in mediating immune cell infiltration. The target gene validation confirmed that DLC1 expression was downregulated in tumor samples. The target protein level was consistently downregulated in tumor samples.

Conclusions: DLC1 levels might be useful in predicting the prognosis of patients with UCEC and especially governing the status of tumor microenvironment transition from immune-dominant to metabolic-dominant. The findings shed a different light on the immune therapeutics of UCEC.

Keywords: deleted in liver cancer 1 (DLC1); endometrial neoplasms; immune cell infiltration; macrophages M2; metastasis suppressor gene; prognosis-related biomarker; tumor microenvironment remodeling.