Deciphering the impact of STAT3 activation mediated by PTPRT promoter hypermethylation as biomarker of response to paclitaxel-plus-cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck

IF 2.3 3区医学 Q1 OTORHINOLARYNGOLOGY

Head and Neck-Journal for the Sciences and Specialties of the Head and Neck Pub Date : 2024-07-27 DOI:10.1002/hed.27892

Beatriz Cirauqui Cirauqui MD, PhD, Adrià Bernat Peguera PhD, Ariadna Quer Pi-Sunyer MD, Angelica Ferrando-Díez MD, Jose Luis Ramírez Serrano PhD, Marta Domenech Viñolas MD, Iris Teruel García MD, Vanesa Quiroga García MD, PhD, Imane Chaib Oukadour PhD, Andrea González Valencia MSc, Pilar Hernández Vergara MSN, Itziar de Aguirre Egaña PhD, Cristina Queralt Herrero PhD, Oscar Mesía Carbonell MSc, Assumpció López Paradís MD, Anna Esteve PhD, Mireia Margelí Vila MD, PhD, Rafael Rosell MD, PhD, Anna Martínez-Cardús PhD, Ricard Mesía MD, PhD

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引用次数: 0

Abstract

Background

Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor prognosis. It is known that the activation of STAT3 signaling pathways promotes the development and progression of this neoplasia and it has been described the role of PTPRT as a negative regulator of STAT3. Then, we have evaluated the impact of them as biomarkers of outcome in a series of patients with recurrent and/or metastatic SCCHN treated with weekly paclitaxel-plus-cetuximab (ERBITAX) regimen.

Patients and methods

Between 2008 and 2017, 52 patients with recurrent/metastatic SCCHN were treated with ERBITAX at our center, 34 of whom had available tumor samples. Phosphorylated STAT3 (pSTAT3) protein expression was analyzed by immunohistochemistry, STAT3 mRNA expression by qPCR, and PTPRT promoter methylation by methylation-specific PCR. Molecular results were correlated with response rate (RR), progression-free survival (PFS), and overall survival (OS).

Results

pSTAT3 overexpression was detected in 67% and PTPRT promoter hypermethylation in 41% of tumor samples. PTPRT promoter hypermethylation showed a trend towards an association with lower RR (21% vs. 60%; p = 0.06). A lower RR was also observed in patients with pSTAT3 overexpression (36% vs. 54%) and in those with high STAT3 mRNA levels (43% vs. 64%), but these differences did not reach statistical significance. PTPRT promoter hypermethylation correlated with pSTAT3 overexpression (p = 0.009) but not with STAT3 mRNA overexpression. OS and PFS was shorter in patients with activated STAT3, but the difference did not reach statistical significance.

Conclusions

Although this was a relatively small retrospective study, it provides preliminary indications of the potential role of the STAT3 pathway on outcome in SCCHN and confirms that PTPRT acts as a negative regulator of STAT3. Our findings warrant investigation in a larger patient cohort to determine if inactivating this pathway through specific targeted treatments could improve outcomes in recurrent/metastatic SCCHN patients.

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解密PTPRT启动子超甲基化介导的STAT3激活作为紫杉醇加西妥昔单抗治疗头颈部复发性或转移性鳞状细胞癌患者反应的生物标志物的影响

背景头颈部鳞状细胞癌（SCCHN）是一种侵袭性疾病，预后较差。众所周知，STAT3 信号通路的激活会促进这种肿瘤的发生和发展，而 PTPRT 是 STAT3 的负调控因子。随后，我们在一系列接受每周紫杉醇加西妥昔单抗（ERBITAX）方案治疗的复发性和/或转移性SCCHN患者中评估了它们作为生物标志物对预后的影响。患者和方法2008年至2017年间，我们中心有52名复发性/转移性SCCHN患者接受了ERBITAX治疗，其中34人有可用的肿瘤样本。通过免疫组化分析磷酸化STAT3（pSTAT3）蛋白表达，通过qPCR分析STAT3 mRNA表达，通过甲基化特异性PCR分析PTPRT启动子甲基化。分子结果与反应率（RR）、无进展生存期（PFS）和总生存期（OS）相关。PTPRT启动子高甲基化显示出与较低RR相关的趋势（21% vs. 60%; p = 0.06）。在 pSTAT3 过表达（36% 对 54%）和 STAT3 mRNA 水平较高的患者中也观察到较低的 RR（43% 对 64%），但这些差异未达到统计学意义。PTPRT启动子高甲基化与pSTAT3过表达相关（p = 0.009），但与STAT3 mRNA过表达无关。结论虽然这是一项相对较小的回顾性研究，但它初步表明了 STAT3 通路对 SCCHN 预后的潜在作用，并证实了 PTPRT 是 STAT3 的负调控因子。我们的研究结果值得在更大的患者群体中进行调查，以确定通过特定的靶向治疗使该通路失活是否能改善复发性/转移性 SCCHN 患者的预后。

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

Head and Neck-Journal for the Sciences and Specialties of the Head and Neck 医学-耳鼻喉科学

CiteScore

7.00

自引率

6.90%

发文量

278

审稿时长

1.6 months

期刊介绍： Head & Neck is an international multidisciplinary publication of original contributions concerning the diagnosis and management of diseases of the head and neck. This area involves the overlapping interests and expertise of several surgical and medical specialties, including general surgery, neurosurgery, otolaryngology, plastic surgery, oral surgery, dermatology, ophthalmology, pathology, radiotherapy, medical oncology, and the corresponding basic sciences.