FGL2 is positively correlated with enhanced antitumor responses mediated by T cells in lung adenocarcinoma

Kai Yuan; Yanyan Feng; Hesong Wang; Lu Zhao; Wei Wang; Ting Wang; Yuyin Feng; Guangrui Huang; Anlong Xu

doi:10.7717/peerj.8654

FGL2 is positively correlated with enhanced antitumor responses mediated by T cells in lung adenocarcinoma

PeerJ. 2020 Mar 13:8:e8654. doi: 10.7717/peerj.8654. eCollection 2020.

Authors

Kai Yuan^#^{1

2}, Yanyan Feng^#¹, Hesong Wang¹, Lu Zhao¹, Wei Wang¹, Ting Wang¹, Yuyin Feng¹, Guangrui Huang¹, Anlong Xu^{1

3}

Affiliations

¹ School of Life Sciences, Beijing University of Chinese Medicine, Beijing, Beijing, China.
² Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, United States of America.
³ State Key Laboratory of Biocontrol, Department of Biochemistry, School of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou, Guangdong, China.

^# Contributed equally.

Abstract

Lung cancer is the most common malignant tumor, accounting for 25% of cancer-related deaths and 14% of new cancers worldwide. Lung adenocarcinoma is the most common type of pulmonary cancer. Although there have been some improvements in the traditional therapy of lung cancer, the outcome and prognosis of patients remain poor. Lung cancer is the leading cause of cancer-related deaths worldwide, with 1.8 million new cases being diagnosed each year. Precision medicine based on genetic alterations is considered a new strategy of lung cancer treatment that requires highly specific biomarkers for precision diagnosis and treatment. Fibrinogen-like protein 2 (FGL2) plays important roles in both innate and adaptive immunity. However, the diagnostic value of FGL2 in lung cancer is largely unknown. In this study, we systematically investigated the expression profile and potential functions of FGL2 in lung adenocarcinoma. We used the TCGA and Oncomine datasets to compare the FGL2 expression levels between lung adenocarcinoma and adjacent normal tissues. We utilized the GEPIA, PrognoScan and Kaplan-Meier plotter databases to analyze the relationship between FGL2 expression and the survival of lung adenocarcinoma patients. Then, we investigated the potential roles of FGL2 in lung adenocarcinoma with the TIMER database and functional enrichment analyses. We found that FGL2 expression was significantly lower in lung adenocarcinoma tissue compared with adjacent normal tissue. A high expression level of FGL2 was correlated with better prognostic outcomes of lung adenocarcinoma patients, including overall survival and progression-free survival. FGL2 was positively correlated with the infiltration of immune cells, including dendritic cells, CD8⁺ T cells, macrophages, B cells, and CD4⁺ T cells, in lung adenocarcinoma. Functional enrichment analyses also showed that a high expression level of FGL2 was positively correlated with enhanced T cell activities, especially CD8⁺ T cell activation. Thus, we propose that high FGL2 expression, which is positively associated with enhanced antitumor activities mediated by T cells, is a beneficial marker for lung adenocarcinoma treatment outcomes.

Keywords: Bioinformatics; FGL2; Lung cancer; Prognosis; Tumor infiltrating lymphocyte.

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant numbers 81430099, 31500704, and 81904142], Projects of International Cooperation and Exchanges [grant number 2014DFA32950] and research program from Beijing University of Chinese Medicine [grant numbers 1000041510049, BUCM-2019-JCRC006 and 2019-JYB-TD013]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.