Low expression of IL6R predicts poor prognosis for lung adenocarcinoma

Gaofeng Sun; Tianyi Wang; Muqi Shi; Hao Zhou; Jinjie Wang; Zhanghao Huang; Haijian Zhang; Jiahai Shi

doi:10.21037/atm-21-36

Low expression of IL6R predicts poor prognosis for lung adenocarcinoma

Ann Transl Med. 2021 Jul;9(13):1057. doi: 10.21037/atm-21-36.

Authors

Gaofeng Sun^{1

2}, Tianyi Wang^{1

2}, Muqi Shi³, Hao Zhou^{1

2}, Jinjie Wang^{1

2}, Zhanghao Huang^{1

2}, Haijian Zhang⁴, Jiahai Shi^{1

2}

Affiliations

¹ Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases, and Research Institution of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Nantong, China.
² Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
³ Medical College of Nantong University, Nantong China.
⁴ Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Abstract

Background: Interleukin 6 (IL6) is both a pleiotropic cytokine and an immune-related gene. Interleukin 6 receptor (IL6R) is the receptor for IL6. It may be closely connected to the development of lung cancer. This research aims to explore the prognostic value of IL6R and prevent overtreatment of patients with lung adenocarcinoma (LUAD).

Methods: In this study, the expression of IL6R in tumor tissues and surrounding tissues was first analyzed by immunohistochemistry in the Affiliated Hospital of Nantong University (NTU) cohort. Secondly, we downloaded information from The Cancer Genome Atlas (TCGA) for the TCGA cohort and used this information to explore the messenger RNA (mRNA) level of IL6R. We then used Kaplan-Meier survival analyses, univariate and multivariate Cox analyses, nomogram models, and decision curve analyses to assess the prognostic value of IL6R. In addition, we also analyzed immune cell infiltration and the signaling pathways related to IL6R through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).

Results: Through the data analysis of the NTU cohort and the TCGA cohort, it was found that the expression of IL6R in normal tissues around the tumor was higher than that in tumor tissue, and was positively correlated with the overall survival (OS) of LUAD patients. Additionally, low expression of IL6R was found to be an independent predictor of poor prognosis among the patients in these two research cohorts. Next, using GO, KEGG, and GSEA analyses, we found that partially infiltrated tumor immune cells might be related to earlier staging and better prognosis of patients with LUAD. Finally, the study of the 3-5-year survival rate of LUAD patients through the nomogram showed that the expression of IL6R could improve the accuracy of prediction to prevent the overtreatment of some LUAD patients.

Conclusions: In summary, our study indicated that the low expression of IL6R was associated with poor prognosis among LUAD patients and that low expression of IL6R is a potential independent risk factor that could provide a basis for strengthening postoperative classification management of such patients.

Keywords: Interleukin 6 receptor (IL6R); Kyoto Encyclopedia of Genes and Genomes (KEGG); lung adenocarcinoma (LUAD); prognosis; risk factor.