학술논문
Transcriptomic FHIT low /pHER2 high signature as a predictive factor of outcome and immunotherapy response in non-small cell lung cancer.
Document Type
Academic Journal
Author
Brisebarre A; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; Ancel J; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; CHU Reims, Hôpital Maison Blanche, Service de Pneumologie, Reims, France.; Ponchel T; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; Loeffler E; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; Germain A; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; Dalstein V; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; CHU Reims, Pôle de Biologie Territoriale, Service de Pathologie, Reims, France.; Dormoy V; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; Durlach A; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; CHU Reims, Pôle de Biologie Territoriale, Service de Pathologie, Reims, France.; Delepine G; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; CHU Reims, Hôpital Robert Debré, Service de Chirurgie cardio-vasculaire et thoracique, Reims, France.; Deslée G; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; CHU Reims, Hôpital Maison Blanche, Service de Pneumologie, Reims, France.; Polette M; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.; CHU Reims, Pôle de Biologie Territoriale, Service de Pathologie, Reims, France.; Nawrocki-Raby B; INSERM, Université de Reims Champagne-Ardenne, P3Cell, UMR-S 1250, SFR CAP Santé, Reims, France.
Source
Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Subject
Language
English
Abstract
Introduction: In recent decades, the development of immunotherapy and targeted therapies has considerably improved the outcome of non-small cell lung cancer (NSCLC) patients. Despite these impressive clinical benefits, new biomarkers are needed for an accurate stratification of NSCLC patients and a more personalized management. We recently showed that the tumor suppressor fragile histidine triad (FHIT), frequently lost in NSCLC, controls HER2 receptor activity in lung tumor cells and that tumor cells from NSCLC patients harboring a FHIT low /pHER2 high phenotype are sensitive to anti-HER2 drugs. Here, we sought to identify the transcriptomic signature of this phenotype and evaluate its clinical significance.
Materials and Methods: We performed RNA sequencing analysis on tumor cells isolated from NSCLC (n=12) according to FHIT/pHER2 status and a functional analysis of differentially regulated genes. We also investigated the FHITlow /pHER2 high signature in The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) (n=489) and lung squamous cell carcinoma (LUSC) (n=493) cohorts and used the tumor immune dysfunction and exclusion (TIDE) model to test the ability of this signature to predict response to immune checkpoint inhibitors (ICI).
Results: We showed that up-regulated genes in FHITlow /pHER2 high tumors were associated with cell proliferation, metabolism and metastasis, whereas down-regulated genes were related to immune response. The FHIT low /pHER2 high signature was associated with the higher size of tumors, lymph node involvement, and late TNM stages in LUAD and LUSC cohorts. It was identified as an independent predictor of overall survival (OS) in LUAD cohort. FHIT low /pHER2 high tumors were also predictive of poor response to ICI in both LUAD and LUSC cohorts.
Conclusion: These data suggest that ICI might not be a relevant option for NSCLC patients with FHITlow /pHER2 high tumors and that anti-HER2 targeted therapy could be a good therapeutic alternative for this molecular subclass with poorer prognosis.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Brisebarre, Ancel, Ponchel, Loeffler, Germain, Dalstein, Dormoy, Durlach, Delepine, Deslée, Polette and Nawrocki-Raby.)
Materials and Methods: We performed RNA sequencing analysis on tumor cells isolated from NSCLC (n=12) according to FHIT/pHER2 status and a functional analysis of differentially regulated genes. We also investigated the FHIT
Results: We showed that up-regulated genes in FHIT
Conclusion: These data suggest that ICI might not be a relevant option for NSCLC patients with FHIT
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Brisebarre, Ancel, Ponchel, Loeffler, Germain, Dalstein, Dormoy, Durlach, Delepine, Deslée, Polette and Nawrocki-Raby.)