Comprehensive Molecular Characterizations of Chinese Patients With Different Subtypes of Lung Squamous Cell Carcinoma

Qian, Jie; Chen, Rongrong; Zhao, Ruiying; Han, Yuchen; Yang, Yu

doi:10.3389/fonc.2020.607130

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…1 A and B ), their poor differentiation mimicking either basaloid squamous or uncommitted surface bronchial cells ( Fig. 1 C and D ), and the occurrence of gene alterations and CNVs common to either ADC (e.g., EGFR , NF1 , TP53 , IGF1R ) or SQC (e.g., NF1 , TP53 , CCND1 , IGF1R , CCND3 ) 22 , 23 , 24 , 25 ( Table 2 ) are likely to suggest an origin from a subset of p40+/TTF1+ stem-like basal cells normally existing in distal airways ( Supplementary Fig. 2 A and C ).…”

Section: Discussionmentioning

confidence: 99%

Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations

Pelosi

Bulloni

Vescio

et al. 2021

JTO Clinical and Research Reports

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Introduction Double occurrence of TTF1 and ΔNp63/p40 (henceforth, p40) within the same individual cells is exceedingly rare in lung cancer. Little is known on their biological and clinical implications. Methods Two index cases immunoreactive for both p40 and TTF1 and nine tumors selected from The Cancer Genome Atlas (TCGA) according to the mRNA levels of the two relevant genes entered the study. Results The two index cases were peripherally located, poorly differentiated, and behaviorally unfavorable carcinomas, which shared widespread p40 and TTF1 decoration within the same individual tumor cells. They also retained SMARCA2 and SMARCA4 expression, while variably stained for p53, cytokeratin 5, and programmed death-ligand 1. A subset of basal cells p40+/TTF1+ could be found in normal distal airways. Biphenotypic glandular and squamous differentiation was unveiled by electron microscopy, along with EGFR , RAD51B , CCND3 , or NF1 mutations and IGF1R , MYC , CCND1 , or CDK2 copy number variations on next-generation sequencing analysis. The nine tumors from TCGA (0.88% of 1018 tumors) shared the same poor prognosis, clinical presentation, and challenging histology and had activated pathways of enhanced angiogenesis and epithelial-mesenchymal transition. Mutation and copy number variation profiles did not differ from the other TCGA tumors. Conclusions Double p40+/TTF1+ lung carcinomas are aggressive and likely underrecognized non–small cell carcinomas, whose origin could reside in double-positive distal airway stem-like basal cells through either de novo-basal-like or differentiating cell mechanisms according to a model of epithelial renewal.

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Section: Discussionmentioning

confidence: 99%

Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations

Pelosi

Bulloni

Vescio

et al. 2021

JTO Clinical and Research Reports

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“…Epidermal growth factor receptor (EGFR) represents as the most frequently mutated driver gene in lung cancer. In comparison with lung adenocarcinoma, EGFR mutations are relatively rare lung squamous cell carcinoma (SCC), with a reported prevalence of 3% to 18% (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). In light of this, the therapeutic value of targeted therapy, EGFR tyrosine kinase inhibitors (EGFR-TKIs), in advanced lung SCC patients lacks in-depth multiple dimensional exploration with large cohorts.…”

Section: Introductionmentioning

confidence: 99%

EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes

et al. 2021

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BackgroundThe therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy.Material and MethodsWe consecutively enrolled stage IV, EGFR-mutant, and EGFR-TKI–treated patients with SCC. Patients with EGFR wild-type lung SCC and EGFR-mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed.ResultsIn total, 28 EGFR-mutant lung SCC, 41 EGFR-mutant lung adenocarcinoma, and 40 EGFR wild-type lung SCC patients were included. Among the patients with EGFR mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 vs. 11.0 months, P<0.001). Comparison of the genomic profiles revealed that EGFR-mutant SCC patients had similar mutation characteristics to EGFR-mutant adenocarcinoma patients, but differed from those with EGFR wild-type SCC. Further exploration of EGFR-mutant SCC revealed that mutations in CREBBP (P = 0.005), ZNF217 (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in GRM8 (P = 0.025) were associated with improved PFS.ConclusionsEGFR-mutant lung SCC has a worse prognosis than EGFR-mutant adenocarcinoma. Mutations in other genes, such as CREBBP, ZNF217, GRM8, or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with EGFR-mutant SCCs receiving EGFR-TKIs.

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“…For example, among the reported c-Met inhibitors, crizotinib and cabozantinib are approved for the treatment of nonsmall-cell lung cancer and medullary thyroid cancer. 22 – 29 To date, no selective c-Met kinase inhibitors have been approved for clinical use. Based on the inhibitory results from the ELISA kinase assay, chalcone-1,3,4-thiadiazole hybrid ZW97 selectively and potently inhibited c-Met kinase with an IC 50 of 27.96 nM.…”

Section: Discussionmentioning

confidence: 99%

A novel anti-lung cancer agent inhibits proliferation and epithelial–mesenchymal transition

Zhao

Guo

et al. 2022

J Int Med Res

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Objective To synthesize a novel chalcone-1,3,4-thiadiazole hybrid and investigate its anticancer effects against NCI-H460 cells. Methods ( E)-3-(4-bromophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one, 1,3-dibromopropane and 1,3,4-thiadiazole-2-thiol were used as chemical materials to synthesize compound ZW97. The NCI-H460 lung cancer cell line was selected to explore the antitumor effects of compound ZW97 in vitro and in vivo. Results Compound ZW97 selectively inhibited cell proliferation against lung cancer cell lines NCI-H460, HCC-44 and NCI-H3122 with IC50 values of 0.15 μM, 2.06 μM and 1.17 μM, respectively. ZW97 suppressed migration and the epithelial–mesenchymal transition process in NCI-H460 cells in a concentration-dependent manner. Based on the kinase activity results and docking analysis, compound ZW97 is a novel tyrosine-protein kinase Met (c-Met kinase) inhibitor. It also inhibited NCI-H460 cell growth in xenograft models without obvious toxicity to normal tissues. Conclusions Compound ZW97 is a potential c-Met inhibitor that might be a promising agent to treat lung cancer by inhibiting the epithelial–mesenchymal transition process.

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Comprehensive Molecular Characterizations of Chinese Patients With Different Subtypes of Lung Squamous Cell Carcinoma

Cited by 6 publications

References 37 publications

Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations

Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations

EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes

A novel anti-lung cancer agent inhibits proliferation and epithelial–mesenchymal transition

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