Genetic alteration and PD-L1 expression profiles of Chinese patients with lung squamous cell carcinoma

Despite the achievements made in treating lung cancer during the past decades, lung cancer still leads in cancer incidence and mortality worldwide. Compared to lung adenocarcinoma, the gene mutation profiles of Chinese lung squamous cell carcinoma (SQCC) have not been well established yet.

488 Chinese SQCC patients were enrolled from 2017 to 2020, and 289 of them provided archived tumor specimens for genetic testing, 199 provided plasma instead. All samples were subjected to next-generation sequencing assay (295 took testing of 14 lung cancer-related genes, and the rest took the expanded panel). 120 patients provided blood samples applying for germline mutation testing using expanded panel. Moreover, 144 cases with enough tissue samples underwent PD-L1 immunohistochemical assay.

Of the 488 patients with SQCC, 444 (90.98%) were proved to have at least one alteration in the 14 lung cancer-related genes. Compared with SQCC patients in The Cancer Genome Atlas (TCGA) database, a significant higher mutated frequency of EGFR (16.03% vs. 3.35%), ERBB2 (9.06% vs. 1.68%), KRAS (7.76% vs. 1.22%), and ALK (5.92% vs. 2.23%) was found in our cohort. Totally, 37.50% of patients were identified with actionable alterations, and most of them were detected in the testing using expanded panel than only the driver gene panel (49.22% vs. 29.83%, p < 0.01). Meanwhile, TP53, PIK3CA and actionable alterations were more identified in the genotyping on the tissue samples than the blood circulating tumor DNA (ctDNA). However, genes associated with clonal hematopoiesis, including KMT2D and RB1, were more prevalent in the plasma ctDNA samples. Of 120 patients undertook germline genetic testing, 5 (4.17%) patients were identified with six pathogenic/ likely pathogenic (P/LP) germline variants in DNA damage repair genes. Positive PD-L1 expression was identified in 61.27% of patients, presenting with a significantly positive correlation with KRAS alterations (58.33% vs. 16.67%).

Our study identified unique genomic profiles of Chinese SQCC patients and provided novel insights into the detection of additional actionable genes and ctDNA in further genotyping. Genetic testing on expanded panel merits further study to comprehensive understanding the therapeutic value of targetable alterations in Chinses SQCC patients.