γH2AX, a DNA Double-Strand Break Marker, Correlates with PD-L1 Expression in Smoking-Related Lung Adenocarcinoma

International Journal of Molecular Sciences

Eiko Sakurai¹  Ayano Michiba¹  Yuka Kiriyama¹  Tetsuya Tsukamoto¹  Yasushi Hoshikawa²  Hisato Ishizawa² 

[1] Department of Diagnostic Pathology, Graduate School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Japan;Department of Thoracic Surgery, Graduate School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Japan;

关键词: lung cancer;    adenocarcinoma;    squamous cell carcinoma;    immune checkpoint inhibitors;    programmed death-ligand 1;    DNA damage response;   

DOI  :  10.3390/ijms23126679

来源: DOAJ

【 摘 要 】

In recent years, the choice of immune checkpoint inhibitors (ICIs) as a treatment based on high expression of programmed death-ligand 1 (PD-L1) in lung cancers has been increasing in prevalence. The high expression of PD-L1 could be a predictor of ICI efficacy as well as high tumor mutation burden (TMB), which is determined using next-generation sequencing (NGS). However, a great deal of effort is required to perform NGS to determine TMB. The present study focused on γH2AX, a double-strand DNA break marker, and the suspected positive relation between TMB and γH2AX was investigated. We assessed the possibility of γH2AX being an alternative marker of TMB or PD-L1. One hundred formalin-fixed, paraffin-embedded specimens of lung cancer were examined. All of the patients in the study received thoracic surgery, having been diagnosed with lung adenocarcinoma or squamous cell carcinoma. The expressions of γH2AX and PD-L1 (clone: SP142) were evaluated immunohistochemically. Other immunohistochemical indicators, p53 and Ki-67, were also used to estimate the relationships of γH2AX. Positive relationships between γH2AX and PD-L1 were proven, especially in lung adenocarcinoma. Tobacco consumption was associated with higher expression of γH2AX, PD-L1, Ki-67, and p53. In conclusion, the immunoexpression of γH2AX could be a predictor for the adaptation of ICIs as well of as PD-L1 and TMB.

【 授权许可】

Unknown