Identification of a coagulation-related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma

Siqian Yang; Shiqi Chen; Yue Zhao; Tao Wu; Yuquan Wang; Tingting Li; Liwan Fu; Ting Ye; Yue-Qing Hu; Haiquan Chen

doi:10.1111/1759-7714.15121

Identification of a coagulation-related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma

Thorac Cancer. 2023 Nov;14(33):3295-3308. doi: 10.1111/1759-7714.15121. Epub 2023 Oct 5.

Authors

Siqian Yang^{1

2}, Shiqi Chen^{1

3

4}, Yue Zhao^{1

3

4}, Tao Wu⁵, Yuquan Wang^{1

2}, Tingting Li^{1

2}, Liwan Fu⁶, Ting Ye^{1

3

4}, Yue-Qing Hu^{1

2

7}, Haiquan Chen^{1

2

3

4}

Affiliations

¹ Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.
² Institute of Biostatistics, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
³ Institute of Thoracic Oncology, Fudan University, Shanghai, China.
⁴ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
⁵ Sheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
⁶ Center for Non-communicable Disease Management, Beijing Children's Hospital, Beijing, China.
⁷ Shanghai Center for Mathematical Sciences, Fudan University, Shanghai, China.

Abstract

Background: Lung adenocarcinoma (LUAD) is a fatal form of lung cancer with a poor prognosis. Coagulation system had been confirmed closely related to tumor progression and the hypercoagulable state encouraged the immune infiltration and development of tumor cells, leading to a poor prognosis in cancer patients. However, the use of the coagulation-related genes (CRGs) for prognosis in LUAD has yet to be determined. In this study, we constructed an immune-related signature (CRRS) and identified a potential coagulation-related biomarker (P2RX1).

Methods: We obtained a total of 209 CRGs based on two coagulation-related KEGG pathways, then developed the CRRS signature by using the TCGA-LUAD RNA-seq data via the procedure of LASSO-Cox regression, stepwise-Cox regression, univariate and multivariate Cox regression. Grouped by the CRRS, Kaplan-Meier survival curves and receiver operating characteristic curves were drawn for the training and validation sets, respectively. In addition, single-sample gene set enrichment analysis was exploited to explore immune infiltration level. Moreover, immunophenotypes and immunotherapy grouped by CRRS were further analyzed.

Results: We developed an immune-related signature (CRRS) composed of COL1A2, F2, PLAUR, C4BPA, and P2RX1 in LUAD. CRRS was an independent risk factor for overall survival and displayed stable and powerful performance. Additionally, CRRS possessed distinctly superior accuracy than traditional clinical variables and molecular features. Functional analysis indicated that the differentially high expressed genes in the low-risk group significantly enriched in T cell and B cell receptor signaling pathways. The low-risk group was sensitive to anti-PD-1/PD-L1 immunotherapy and displayed abundant immune infiltration and immune checkpoint gene expression. Finally, we identified an independent prognostic gene P2RX1. Low expression of P2RX1 associated with poor overall survival and decreased immune infiltration.

Conclusions: Our study revealed a significant correlation between CRRS and immune infiltration. CRRS could serve as a promising tool to improve the clinical outcomes for individual LUAD patients.

Keywords: coagulation-related genes; immune infiltration; immunotherapy; lung adenocarcinoma; prognosis.

MeSH terms

Adenocarcinoma of Lung* / genetics
Humans
Immunotherapy
Lung Neoplasms* / genetics
Prognosis

Substances

Collagen Type I, alpha2 Subunit

Abstract

MeSH terms

Substances

Grants and funding