P006 Evaluation of Efficacy and Safety of Uniportal Segmentectomy in the Treatment of Small Lung Nodule

Abstract

Background: Lung adenosquamous carcinomas (ASC) are morphologically mixed tumors that contain the two cell components adenocarcinomas (AC) and squamous cell carcinomas (SCC). However, to date, the genomic profile, TMB status, evolutionary relationship, and immune microenvironment of the two components still remain unclear. Method: Adenocarcinomas component (ACC) and squamous cell carcinomas component (SCCC) in ASC (n¼30) were validated by immunohistochemistry and obtained separately by means of laser capture microdissection. Gene panel and T cell receptor (TCR) repertoire sequencing were performed in both components. Normal tissues adjacent to the cancer were used as controls. The two components were compared from the dimension of somatic mutations, TMB, evolution, and the TCR clones. 626 AC tumors and 83 SCC tumors were also included for comparison with ASC. Results: Comparison of frequency of recurrently altered genes in lung SCCC, ACC, AC, and SCC were performed. EGFR (Fisher Exact test, p¼0.0476, OR 2.6) and MAP3K1 (p¼0.0020, OR 10.2) were enriched but no KRAS were found in ACC compared to AC. Compared with SCC, EGFR (p<0.0001, OR 14.3) is enriched in SCCC, while TP53 (p¼0.0129, OR 0.3) with lower mutation frequency. Different mutational spectra suggest that ACC is different from AC, and SCCC is different from SCC. Despite the heterogeneity, there were shared mutations in lung SCCC and ACC. 79% of ACC and 75% of SCCC samples harbored EGFR mutations. 46% of ACC and 64% of SCCC samples harbored TP53 mutations. In the evolutionary tree analysis, EGFR (in 75% of patients) and TP53 (43%) are the most frequent trunk genes. Above 90% (27/28) of patients had trunk genes, indicating that SCCC and ACC in ASC come from the same origin. In ACC, SCCC, AC, and SCC, 14%, 29%, 23%, and 48% of samples were identified as TMB-H respectively. The TMB index of SCCC was higher than that of ACC (Wilcoxon matched pairs test, p¼0.0065). The ACC TMB was equivalent to AC (Mann-Whitney test, p¼0.9352). The SCCC TMB is marginally lower than SCC (Mann-Whitney test, p¼0.0553). Significant difference is showed in the diversity of TCRs between ACC and SCCC (Wilcoxon matched pairs test, p¼0.0383). Although the difference is not significant, 65% (14/20) of SCC samples have a higher clonality index than ACC. Conclusion: Our study promote a better knowledge about ACC and SCCC from ASC, supporting the hypothesis that ACC and SCCC in ASC come from the same origin. However, two components also exhibit diverse genomic profile, TMB status, and TCR repertoire.