KLRB1 expression is associated with lung adenocarcinoma prognosis and immune infiltration and regulates lung adenocarcinoma cell proliferation and metastasis through the MAPK/ERK pathway

Siwei Xu; Yujian Xu; Wenjun Chai; Xiaoli Liu; Jing Li; Lei Sun; Hongyu Pan; Mingxia Yan

doi:10.21037/jtd-24-8

KLRB1 expression is associated with lung adenocarcinoma prognosis and immune infiltration and regulates lung adenocarcinoma cell proliferation and metastasis through the MAPK/ERK pathway

J Thorac Dis. 2024 Jun 30;16(6):3764-3781. doi: 10.21037/jtd-24-8. Epub 2024 Jun 28.

Authors

Siwei Xu^#^{1

2}, Yujian Xu^#^{1

2}, Wenjun Chai^{1

2}, Xiaoli Liu^{1

2}, Jing Li^{1

2}, Lei Sun^{1

2}, Hongyu Pan^{1

2}, Mingxia Yan^{1

2}

Affiliations

¹ Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

^# Contributed equally.

Abstract

Background: Lung cancer is the most common primary malignant tumor of the lung, and as one of the malignant tumors that pose the greatest threat to the health of the population, the incidence rate has remained high in recent years. Previous studies have shown that KLRB1 is transcriptionally repressed in lung adenocarcinoma and correlates with lung adenocarcinoma prognosis. The objective of this study is to investigate the intrinsic mechanisms by which KLRB1 affects the malignant phenotypes of lung adenocarcinoma such as immune infiltration, proliferation, growth and metastasis.

Methods: We assessed the expression levels of KLRB1 in publicly available databases and investigated its associations with clinical and pathological variables. Enrichment analysis was subsequently conducted to investigate possible signaling pathways and their associated biological functions. Statistical analysis, including Spearman correlation and the application of multigene prediction models, was utilized to assess the relationship between the expression of KLRB1 and the infiltration of immune cells. The diagnostic and prognostic value of KLRB1 was evaluated using Kaplan-Meier survival curves, diagnostic receptor operating characteristic (ROC) curves, histogram models, and Cox regression analysis. Specimens from lung adenocarcinoma (LUAD) patients were collected, the expression level of KLRB1 was detected by protein blotting analysis, and the expression level of KLRB1 was detected at the mRNA level by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Small interfering RNA (siRNA) was used to silence gene expression, and Transwell, Cell Counting Kit-8 (CCK-8) and colony formation assays were subsequently performed to analyze the effects of KLRB1 on LUAD cell migration, invasion and proliferation.

Results: KLRB1 expression was lower in lung cancer tissue than in surrounding healthy tissue. Genes differentially expressed in the low and high KLRB1 expression groups were found to be significantly enriched in pathways related to immunity. KLRB1 exerted an impact on the MAPK/ERK signaling pathway, thereby modulating the growth and proliferation of LUAD cells. KLRB1 expression is linked to prognosis, immune infiltration, and cell migration and proliferation in LUAD.

Conclusions: The evidence revealed a correlation between KLRB1 and both prognosis and immune infiltration in LUAD patients.

Keywords: KLRB1; Lung adenocarcinoma (LUAD); MAPK/ERK signaling pathway; immune infiltration; prognostic implications.