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

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.

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Circular RNA expression profile of lung squamous cell carcinoma: identification of potential biomarkers and therapeutic targets

Bioscience Reports ◽

10.1042/bsr20194512 ◽

2020 ◽

Vol 40 (4) ◽

Cited By ~ 1

Author(s):

Yawei Wang ◽

Haiyan Zhang ◽

Jian Wang ◽

Bei Li ◽

Xiuwen Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Expression Profile ◽

Squamous Cell ◽

High Throughput Sequencing ◽

Expression Profiles ◽

Lung Squamous Cell Carcinoma ◽

Circular Rnas ◽

Diagnostic Biomarkers ◽

Diagnostic Potential

Abstract Emerging evidences indicated that exosomal circular RNAs (circRNAs) could serve as diagnostic biomarkers for cancers. However, the expression profiles and clinical significance of circRNAs in lung squamous cell carcinoma (LUSC) remain largely unknown. Herein, we analyzed circRNAs expression profile in six pairs of plasma exosome samples of LUSC patients using high-throughput sequencing. A total of 252 differentially expressed exosomal circRNAs were identified, including 133 up-regulated circRNAs and 119 down-regulated circRNAs. Subsequently, the circRNAs–miRNAs–mRNAs interaction network was built to investigate potential function of circRNAs. Three up-regulated circRNAs (hsa_circ_0014235, hsa_circ_0025580 and hsa_circ_0026403) were implied to participate in cancer-related pathways. QRT-PCR experiment confirmed the up-regulation of hsa_circ_0014235 and hsa_circ_0025580. Finally, clinical studies indicated that hsa_circ_0014235 and hsa_circ_0025580 could serve as novel diagnostic biomarkers for LUSC. Taken together, our study revealed exosomal circRNAs expression profile in LUSC for the first time and showed the important diagnostic potential for circRNAs in LUSC.

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Comprehensive genomic profiling in Chinese patients with lung squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.8540 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 8540-8540

Author(s):

Zuping Lian ◽

Heng Li ◽

Youming Lei ◽

Lei Xian ◽

Kunpeng Bu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Lung Squamous Cell Carcinoma ◽

Copy Number Variations ◽

Chinese Patients ◽

Mutation Rates ◽

Genomic Alteration ◽

Genomic Alterations ◽

Genomic Features

8540 Background: Lung squamous cell carcinoma (LUSC) is a major histological subtype of non-small cell lung cancer (NSCLC) and accounts for 30% of NSCLC. Previous studies had revealed the genomic characterization of LUSC in Western patients (pts). However, the comprehensive genomic features of LUSC in Chinese pts have not been well understood. Methods: Deep sequencing targeting 450 cancer genes was performed on FFPE and matching blood samples collected from 311 LUSC pts. Genomic alterations (GAs) including single nucleotide variations, short and long insertions and deletions, copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Results: The median age of LUSC pts was 63 years old (range 57-68.5), of which 88% were male. The most frequently mutated genes were TP53 (88%), PIK3CA (34%), CDKN2A (33%), SOX2 (26%), LRP1B (22%), KLHL6 (21%), KMT2D (19%), PRKCI (19%), NFE2L2 (18%) and MAP3K13 (17%). Interestingly the mutation rates of PIK3CA (p = 1.93e-05) and CDKN2A (p = 2.48e-05) were significantly higher than that in TCGA cohort. Genomic alterations in eight druggable genes recommended by the NCCN guideline occurred in 32% of pts, and alterations to PI3K/mTOR signaling pathway related genes occurred in 52% of pts. One patient with PIK3CA amplification achieved stable disease for eight months after everolimus treatment. Moreover, variants in the homologous recombination (HR) pathway were identified in 17% of pts. The median TMB of LUSC pts was 10.8 Muts/MB (range 6.9-14.5 Muts/MB) which was higher than Western populations [PMID: 28420421]. The 1st Quartile (TMB-L), median and 3rd Quartile (TMB-H) TMB value was 6.9, 10.8 and 14.5 Muts/Mb respectively. Comparing with the TMB-L group, frequencies of CDKN2A (39% vs 19%, p= 0.005), LRP1B (45% vs 8%, p< 0.001) and KMT2D (27% vs 8%, p= 0.002) were higher in TMB-H group. Conclusions: In summary, we characterized the genomic alteration profile of Chinese LUSC pts. Consistent with previous reports, high mutation rates of TP53, PIK3CA and CDKN2A are the most important genomic features of LUSC. However, the proportion of PIK3CA and CDKN2A mutations in Chinese LUSC pts is higher than that of Western populations. In addition, we also found targetable pathways (including PI3K/mTOR) along with gene related variations and high TMB in many pts, providing potential targeted therapy and immunotherapy options for LUSC pts.

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