Abstract

BackgroundThis study aims to profile integrative genomic spectra of Chinese patients with different subtypes of lung squamous cell carcinoma (LUSC) and explore potential molecular prognosis factors.MethodsWe retrospectively identified 204 surgically resected LUSC patients in Shanghai Chest Hospital who underwent capture-based targeted next-generation sequencing (NGS) with a panel of 68 lung cancer‐related genes from September 2017 to January 2019. NGS was used to profile comprehensive molecular characterizations.ResultsOf 204 cases, 114 (55.9%) were keratinizing squamous cell carcinoma (KSCC), 77 (37.7%) were non-keratinizing squamous cell carcinoma (NKSCC), 13 (6.4%) were basaloid squamous cell carcinoma (BSCC), respectively. All subtypes presented similarly high proportions of mutations, including TP53, CDKN2A, and NOTCH1. A comparable prevalence of FGFR1 amplifications was identified between KSCC and NKSCC (11.4 versus 26.9%, p = 0.007). Compared with NKSCC, IGF1R amplifications were more frequent in BSCC (0 versus 15.4%, p = 0.019). We found cases with TP53 alterations had less EGFR alterations in KSCC (P = 0.013, OR = 0.158). Compared with TCGA cohorts, our Chinese cohorts exhibited statistic differences in both somatic mutations and signaling pathways. We found that STK 11 alterations and TOP2A alterations were significantly associated with higher risk of recurrence in patients with LUSC.ConclusionsSignificant differences exist among three subtypes of LUSC in molecular characterizations.

Highlights

  • Lung cancer has been the malignant tumor with highest incidence and mortality worldwide [1, 2]

  • A comparable prevalence of FGFR1 amplifications was identified between keratinizing squamous cell carcinoma (KSCC) and non-keratinizing squamous cell carcinoma (NKSCC) (11.4 versus 26.9%, p = 0.007)

  • We found that STK 11 alterations and TOP2A alterations were significantly associated with higher risk of recurrence in patients with lung squamous cell carcinoma (LUSC)

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Summary

Introduction

Lung cancer has been the malignant tumor with highest incidence and mortality worldwide [1, 2]. As the most prevalent type of lung cancer, non‐small cell lung cancer (NSCLC) comprises two main histological types: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Second to LUAD, LUSC accounts for approximately 25–30% of lung cancer [3]. With the emergence and progress of molecular targeted therapies, the objective response rates (ORRs) and progression-free survival (PFS) of NSCLC patients treated with gene-directed therapies have been improved compared with traditional cytotoxic chemotherapy [4]. Contrast to numerous studies on molecular characteristics of LUAD, little is known about genetic profiles of LUSC, which might be responsible for sluggish progress of targeted therapies in LUSC. This study aims to profile integrative genomic spectra of Chinese patients with different subtypes of lung squamous cell carcinoma (LUSC) and explore potential molecular prognosis factors

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