Correlation of PD-L1 Expression with Clinicopathological and Genomic Features in Chinese Non-Small-Cell Lung Cancer.
Yue LiChong LiYa JiangXue HanSisi LiuXiuxiu XuWanxiangfu TangQiuxiang OuHua BaoXue WuYang W ShaoMinyan XingYixiang ZhangYuezhen WangPublished in: Journal of oncology (2022)
Programmed cell death 1 ligand 1 (PD-L1) has been approved as predictive biomarker for non-small-cell lung cancer (NSCLC) patients treated with PD-(L)1 blockade therapy. The clinical/genomic features associated with PD-L1 are not well studied. Genomic profiling of tumor biopsies from 883 Chinese NSCLC patients was performed by targeted next-generation sequencing. Immunohistochemical analysis was conducted to evaluate PD-L1 expression levels using antibodies Dako 22C3 and 28-8, respectively. Our study showed distinct correlation between PD-L1 expression and clinical/genomic characteristics when using different PD-L1 antibodies and in different histological subtypes including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), respectively. PD-L1 high expression (22C3) was associated with male and lymph node metastasis only in ADC patients. Furthermore, mutations of TP53 and KRAS , KIF5B-RET fusion, copy number gains of PD-L1 and PD-L2 , and arm-level amplifications of chr.12p were significantly associated with PD-L1 positive status in ADC patients. For SCC patients, the gain of EGFR and MDM2 and loss of PTPRD were negatively associated with PD-L1 expression. We also compared our results with other studies and found conflicting results presumably because of the multiplicity of antibody clones and platforms, the difference of cutoffs for assigning PD-L1 expression levels, and the variation in study populations. Our study can help to understand the utility and validity of PD-L1 as biomarker of response to immune checkpoint inhibitors.
Keyphrases
- copy number
- squamous cell carcinoma
- end stage renal disease
- newly diagnosed
- ejection fraction
- small cell lung cancer
- lymph node metastasis
- prognostic factors
- peritoneal dialysis
- mitochondrial dna
- dna methylation
- gene expression
- bone marrow
- computed tomography
- genome wide
- poor prognosis
- patient reported outcomes
- radiation therapy
- drug delivery
- cell therapy
- brain metastases
- papillary thyroid