Stefano Cavalieri, Cristiana Bergamini, Deborah Lenoci, Arianna Ottini, Marta Lucchetta, Erica Torchia, Lisa Licitra, Loris De Cecco
{"title":"头颈部鳞状细胞癌中的 Claudin-1","authors":"Stefano Cavalieri, Cristiana Bergamini, Deborah Lenoci, Arianna Ottini, Marta Lucchetta, Erica Torchia, Lisa Licitra, Loris De Cecco","doi":"10.1159/000540775","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The objective response rate to immunotherapy is limited in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) patients, whose prognosis is still dismal. Few prognostic factors are clinically available, mostly related to patient or disease characteristics. Gene expression signatures offer better prognostic abilities but are mainly used in research. One such GE model classifies HNSCC into 6 clusters with different prognoses. Claudin-1 (CLDN1), which influences tumor microenvironment and immune cell infiltration, has emerged as a potential target, especially in cancers like HNSCC with high CLDN1 expression.</p><p><strong>Methods: </strong>A single-center cohort of 100 loco-regionally advanced HNSCC patients from the BD2Decide observational study was analyzed. Patients were selected to balance long-term survivors and deceased patients, including HPV-negative and HPV-positive cases. Primary tumor specimens underwent GE analysis using Affymetrix ClariomD chips. Primary endpoint was overall survival (OS).</p><p><strong>Results: </strong>The cohort comprised 100 HNSCC patients with a median age of 60 years, predominantly men (76%). Median OS and disease-free survival (DFS) were 94.24 and 42.79 months, respectively. CLDN1 expression varied significantly among primary sites, being highest in hypopharynx cancers. Differences in expression were not significant when stratified by HPV status or clinical stage. CLDN1 expression differed across the 6 transcriptomic clusters, with the highest levels in clusters associated with mesenchymal and hypoxic features. Higher CLDN1 expression correlated with shorter OS (hazard ratio [HR]: 3, p = 0.0023) and DFS (HR: 2.14, p = 0.02).</p><p><strong>Conclusion: </strong>CLDN1 expression is heterogeneous in HNSCC and carries prognostic significance. It is highest in tumors with HPV-like biology and hypoxic environments, and lowest in immune-sensitive clusters. High CLDN1 is a negative prognostic factor and a promising therapeutic target. Anti-CLDN1 treatments could improve outcomes of CLDN1+ HNSCC patients, and combination therapies with ICIs might overcome resistance in CLDN1- cases. These findings support the need for clinical studies on anti-CLDN1 therapies.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Claudin-1 in Head and Neck Squamous Cell Carcinoma.\",\"authors\":\"Stefano Cavalieri, Cristiana Bergamini, Deborah Lenoci, Arianna Ottini, Marta Lucchetta, Erica Torchia, Lisa Licitra, Loris De Cecco\",\"doi\":\"10.1159/000540775\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>The objective response rate to immunotherapy is limited in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) patients, whose prognosis is still dismal. Few prognostic factors are clinically available, mostly related to patient or disease characteristics. Gene expression signatures offer better prognostic abilities but are mainly used in research. One such GE model classifies HNSCC into 6 clusters with different prognoses. Claudin-1 (CLDN1), which influences tumor microenvironment and immune cell infiltration, has emerged as a potential target, especially in cancers like HNSCC with high CLDN1 expression.</p><p><strong>Methods: </strong>A single-center cohort of 100 loco-regionally advanced HNSCC patients from the BD2Decide observational study was analyzed. Patients were selected to balance long-term survivors and deceased patients, including HPV-negative and HPV-positive cases. Primary tumor specimens underwent GE analysis using Affymetrix ClariomD chips. Primary endpoint was overall survival (OS).</p><p><strong>Results: </strong>The cohort comprised 100 HNSCC patients with a median age of 60 years, predominantly men (76%). Median OS and disease-free survival (DFS) were 94.24 and 42.79 months, respectively. CLDN1 expression varied significantly among primary sites, being highest in hypopharynx cancers. Differences in expression were not significant when stratified by HPV status or clinical stage. CLDN1 expression differed across the 6 transcriptomic clusters, with the highest levels in clusters associated with mesenchymal and hypoxic features. Higher CLDN1 expression correlated with shorter OS (hazard ratio [HR]: 3, p = 0.0023) and DFS (HR: 2.14, p = 0.02).</p><p><strong>Conclusion: </strong>CLDN1 expression is heterogeneous in HNSCC and carries prognostic significance. It is highest in tumors with HPV-like biology and hypoxic environments, and lowest in immune-sensitive clusters. High CLDN1 is a negative prognostic factor and a promising therapeutic target. Anti-CLDN1 treatments could improve outcomes of CLDN1+ HNSCC patients, and combination therapies with ICIs might overcome resistance in CLDN1- cases. These findings support the need for clinical studies on anti-CLDN1 therapies.</p>\",\"PeriodicalId\":19497,\"journal\":{\"name\":\"Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-08-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000540775\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000540775","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Claudin-1 in Head and Neck Squamous Cell Carcinoma.
Introduction: The objective response rate to immunotherapy is limited in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) patients, whose prognosis is still dismal. Few prognostic factors are clinically available, mostly related to patient or disease characteristics. Gene expression signatures offer better prognostic abilities but are mainly used in research. One such GE model classifies HNSCC into 6 clusters with different prognoses. Claudin-1 (CLDN1), which influences tumor microenvironment and immune cell infiltration, has emerged as a potential target, especially in cancers like HNSCC with high CLDN1 expression.
Methods: A single-center cohort of 100 loco-regionally advanced HNSCC patients from the BD2Decide observational study was analyzed. Patients were selected to balance long-term survivors and deceased patients, including HPV-negative and HPV-positive cases. Primary tumor specimens underwent GE analysis using Affymetrix ClariomD chips. Primary endpoint was overall survival (OS).
Results: The cohort comprised 100 HNSCC patients with a median age of 60 years, predominantly men (76%). Median OS and disease-free survival (DFS) were 94.24 and 42.79 months, respectively. CLDN1 expression varied significantly among primary sites, being highest in hypopharynx cancers. Differences in expression were not significant when stratified by HPV status or clinical stage. CLDN1 expression differed across the 6 transcriptomic clusters, with the highest levels in clusters associated with mesenchymal and hypoxic features. Higher CLDN1 expression correlated with shorter OS (hazard ratio [HR]: 3, p = 0.0023) and DFS (HR: 2.14, p = 0.02).
Conclusion: CLDN1 expression is heterogeneous in HNSCC and carries prognostic significance. It is highest in tumors with HPV-like biology and hypoxic environments, and lowest in immune-sensitive clusters. High CLDN1 is a negative prognostic factor and a promising therapeutic target. Anti-CLDN1 treatments could improve outcomes of CLDN1+ HNSCC patients, and combination therapies with ICIs might overcome resistance in CLDN1- cases. These findings support the need for clinical studies on anti-CLDN1 therapies.
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Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.
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