Claudin-1 in Head and Neck Squamous Cell Carcinoma.

IF 2.5 3区医学 Q3 ONCOLOGY Oncology Pub Date : 2024-08-14 DOI:10.1159/000540775

Stefano Cavalieri, Cristiana Bergamini, Deborah Lenoci, Arianna Ottini, Marta Lucchetta, Erica Torchia, Lisa Licitra, Loris De Cecco

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Abstract

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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头颈部鳞状细胞癌中的 Claudin-1

简介复发性/转移性头颈部鳞状细胞癌（HNSCC）患者对免疫疗法的客观反应率有限，其预后仍然不容乐观。临床上可用的预后因素很少，大多与患者或疾病特征有关。基因表达特征具有更好的预后能力，但主要用于研究。其中一个基因表达模型将 HNSCC 分成 6 个预后不同的群组。影响肿瘤微环境和免疫细胞浸润的Claudin-1（CLDN1）已成为一个潜在的靶点，尤其是在HNSCC等CLDN1高表达的癌症中：方法：分析了BD2Decide观察性研究中100名局部区域晚期HNSCC患者的单中心队列。所选患者兼顾了长期存活者和死亡患者，包括HPV阴性和HPV阳性病例。原发肿瘤标本使用 Affymetrix ClariomD 芯片进行基因组学分析。主要终点为总生存期（OS）：组群包括 100 名 HNSCC 患者，中位年龄为 60 岁，主要为男性（76%）。中位OS和无病生存期（DFS）分别为94.24个月和42.79个月。CLDN1的表达在不同原发部位有显著差异，在下咽癌中最高。根据HPV状态或临床分期进行分层后，表达差异并不显著。CLDN1的表达在6个转录组群中各不相同，在与间质和缺氧特征相关的组群中水平最高。较高的CLDN1表达与较短的OS（危险比[HR]：3，p = 0.0023）和DFS（HR：2.14，p = 0.02）相关：结论：CLDN1在HNSCC中的表达是异质性的，具有预后意义。结论：CLDN1在HNSCC中的表达是异质性的，具有预后意义，在具有HPV样生物学特性和缺氧环境的肿瘤中表达量最高，而在免疫敏感的肿瘤群中表达量最低。高CLDN1是一个消极的预后因素，也是一个有希望的治疗靶点。抗CLDN1治疗可改善CLDN1+ HNSCC患者的预后，与ICIs联合治疗可克服CLDN1-病例的耐药性。这些发现支持了进行抗CLDN1疗法临床研究的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： 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.