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Open Access 01-12-2024 | Biomarkers | Research

Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6

Authors: Ren-Hui Xiong, Shuo-Qi Yang, Ji-Wei Li, Xun-kai Shen, Lu-Ming Jin, Chao-Yang Chen, Yu-Ting Yue, Zhi-Chen Yu, Qing-Yu Sun, Wen Jiang, Ming-Zheng Jiang, Xiao-Yan Wang, Shi-Xu Song, Dai Cao, Hong-li Ye, Li-Ran Zhao, Li-Peng Huang, Liang Bu

Published in: Discover Oncology | Issue 1/2024

Abstract

Background

Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear.

Objective

The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance.

Methods

The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses.

Results

PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-β signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed.

Conclusion

PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

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Title: Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6
Authors: Ren-Hui Xiong
Shuo-Qi Yang
Ji-Wei Li
Xun-kai Shen
Lu-Ming Jin
Chao-Yang Chen
Yu-Ting Yue
Zhi-Chen Yu
Qing-Yu Sun
Wen Jiang
Ming-Zheng Jiang
Xiao-Yan Wang
Shi-Xu Song
Dai Cao
Hong-li Ye
Li-Ran Zhao
Li-Peng Huang
Liang Bu
Publication date: 01-12-2024
Publisher: Springer US
Keyword: Biomarkers
Published in: Discover Oncology / Issue 1/2024
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI: https://doi.org/10.1007/s12672-024-00939-9

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