The mutation frequency of HPD related genes in different lung cancer stages.

Abstract

e21006 Background: Clinical detections of hyper-progressive disease (HPD) gene mutations in advanced lung cancer should be considered to avoid the inappropriate immunotherapy, and recently neoadjuvnat and adjuvant immunotherapy also proved to be efficacy in early stage of lung cancer. Nevertheless, it still remains poorly understanding of the distribution of HPD related mutations in early stage lung cancer. Methods: In this study, according to information of patient specimens from public database TCGA, Ⅰ and Ⅱ stages were defined as early stage, Ⅲ and Ⅳ stages were defined as advanced stage. The mutations in HPD related genes were evaluated including CNVs of CCND1, FGF19, FGF3, FGF4, MDM2 and MDM4, and SNVs of DNMT3A. Chi-square test was performed to analyze the differences of HPD related gene mutation frequency in early and advanced stages. Results: Based on the statistics of clinical data from TCGA, we found 399 early stage cases and 110 advanced stage cases in patients with lung adenocarcinoma (LUAD), 402 early stage cases and 91 advanced stage cases in patients with lung squamous cell carcinoma (LUSC). In early stage, we found 76, 76, 76, 75, 89, 201 cases of CNVs of CCND1, FGF19, FGF3, FGF4, MDM2 and MDM4, 10 cases of SNVs of DNMT3A, respectively. In advanced stage, we counted 32, 32, 32, 29, 21, 37 cases of CNVs of CCND1, FGF19, FGF3, FGF4, MDM2 and MDM4, 4 cases of SNVs of DNMT3A, respectively. No significant differences of mutation frequency HPD related gene between early and advanced stages were found via χ2 test. CNVs frequencies of CCND1, FGF19, FGF3, FGF4 and MDM4 in LUAD were significantly lower than them in LUSC. No significant differences of CNVs frequency of MDM2 and SNVs frequency of DNMT3A beween patients with LUAD and patients with LUSC were found. Conclusions: Our analysis indicated that immunotherapy for patients with early stage lung cancer also needed to test these mutations. LUSC patients required paying more attentions on HPD related mutations of which frequencies were significantly higher than LUAD patients. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.