Nucleic acid-sensing-related gene signature in predicting prognosis and treatment efficiency of small cell lung cancer patients

Qianshi Liu; Zhaoshen Li; Na Li; Junjie Liu; Hong Wu; Jie Chen

doi:10.3389/fonc.2024.1394286

Nucleic acid-sensing-related gene signature in predicting prognosis and treatment efficiency of small cell lung cancer patients

Front Oncol. 2024 Apr 12:14:1394286. doi: 10.3389/fonc.2024.1394286. eCollection 2024.

Authors

Qianshi Liu^#^{1

2}, Zhaoshen Li^#^{1

2}, Na Li³, Junjie Liu¹, Hong Wu², Jie Chen¹

Affiliations

¹ Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, China.
² Department of Oncology and Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
³ Shenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd, Shenzhen, China.

^# Contributed equally.

Abstract

Introduction: Nucleic acid-sensing (NAS) pathways could induce innate and adaptive immune responses. However, rare evidence exhibited how the core genes of the NAS pathways affected the immune response and prognosis of small cell lung cancer (SCLC) patients.

Methods: We conducted a comprehensive bioinformatic analysis based on the RNA profiles of 114 SCLC patients, including 79 from cBioPortal, 21 from GSE30219, and 14 from our sequencing data. The multiplex immunohistochemistry (mIHC) was used to characterize the role of NAS related genes in the tumor microenvironment (TME) of SCLC.

Results: A prognostic model (7NAS risk model) was constructed based on 7 NAS-related genes which was demonstrated as an independent prognostic index. The low-risk group was identified to have a better prognosis and an immune-activated microenvironment in both the public datasets and our dataset. Intriguingly, mIHC data showed that CD45⁺ immune cells, CD8⁺ T lymphocytes, and CD68⁺ macrophages were prevalently enriched in low-risk SCLC patients and positively correlated with IRF1 expression. Additionally, Patients in the low-risk group might have superior responses to chemotherapy and immunotherapy.

Conclusion: Conclusively, this study created a new risk model based on genes associated with NAS pathways which could predict the prognosis and response of treatment in patients with SCLC.

Keywords: multiplex immunohistochemistry; nucleic acid sensing-related genes; prognostic signature; small cell lung cancer; tumor microenvironment.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Key Research and Development Projects of Guangxi Science and Technology Department (No. 2022AB11001).