Bone-remodeling-related gene expression in oral squamous cell carcinoma: impact on mandibular invasion and overall survival.

IF 2 3区医学 Q2 Dentistry

Journal of Stomatology Oral and Maxillofacial Surgery Pub Date : 2025-07-18 DOI:10.1016/j.jormas.2025.102505

Érica Fernanda Patricio, Gustavo Davi Rabelo, Carlos Henrique Horst Bianchin, Claudia Malheiros Coutinho-Camillo, Luiz Paulo Kowalski, Clovis Antônio Lopes Pinto, Fabio Abreu Alves

{"title":"Bone-remodeling-related gene expression in oral squamous cell carcinoma: impact on mandibular invasion and overall survival.","authors":"Érica Fernanda Patricio, Gustavo Davi Rabelo, Carlos Henrique Horst Bianchin, Claudia Malheiros Coutinho-Camillo, Luiz Paulo Kowalski, Clovis Antônio Lopes Pinto, Fabio Abreu Alves","doi":"10.1016/j.jormas.2025.102505","DOIUrl":null,"url":null,"abstract":"Objectives: Bone invasion by oral squamous cell carcinoma (OSCC) activates the remodeling process with the participation of RANK/RANKL/OPG and Interleukin 6 (IL-6) genes. This study aimed to evaluate gene expressions of RANK, RANKL, OPG, and IL-6 in OSCC associated with mandibular invasion (MI) and to identify their influence on patients' overall survival (OS).Materials and methods: A cross-sectional study selected patients treated with mandibulectomy for OSCC in a reference center, resulting in two hundred and twenty individuals. Forty age-match patients with material for molecular analysis were included in the study to evaluate RANK, RANKL, OPG, and IL6 expression analysis, divided into 2 groups: MI (n = 20) and no invasion (NI, n = 20). Tumor mRNA expression of the selected genes was determined by real-time polymerase chain reaction (calibrated by endogenous GAPDH and a control pool of non-neoplastic RNA).Results: Gene expression analysis revealed 16 of 36 cases (44%) presenting downregulation for RANK; 28 of 37 samples (75%) with overexpression for RANKL; 19 of 35 samples (54%) with downregulation for IL-6; and 16 of 37 samples (43%) with normal expression for OPG. IL-6 expression was associated with MI, and all the genes were correlated with each other (p < 0.05). Multivariate Cox regression revealed an association of MI and perineural invasion with OS, and higher OS rate was associated with IL-6 downregulation (p = 0.053, 108.5 months).Conclusions: Mandibular invasion may impact overall survival and is associated with IL-6 tumor expression. Downregulation of IL-6 by malignant cells is associated with higher overall survival.","PeriodicalId":56038,"journal":{"name":"Journal of Stomatology Oral and Maxillofacial Surgery","volume":" ","pages":"102505"},"PeriodicalIF":2.0000,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Stomatology Oral and Maxillofacial Surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jormas.2025.102505","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Dentistry","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives: Bone invasion by oral squamous cell carcinoma (OSCC) activates the remodeling process with the participation of RANK/RANKL/OPG and Interleukin 6 (IL-6) genes. This study aimed to evaluate gene expressions of RANK, RANKL, OPG, and IL-6 in OSCC associated with mandibular invasion (MI) and to identify their influence on patients' overall survival (OS).

Materials and methods: A cross-sectional study selected patients treated with mandibulectomy for OSCC in a reference center, resulting in two hundred and twenty individuals. Forty age-match patients with material for molecular analysis were included in the study to evaluate RANK, RANKL, OPG, and IL6 expression analysis, divided into 2 groups: MI (n = 20) and no invasion (NI, n = 20). Tumor mRNA expression of the selected genes was determined by real-time polymerase chain reaction (calibrated by endogenous GAPDH and a control pool of non-neoplastic RNA).

Results: Gene expression analysis revealed 16 of 36 cases (44%) presenting downregulation for RANK; 28 of 37 samples (75%) with overexpression for RANKL; 19 of 35 samples (54%) with downregulation for IL-6; and 16 of 37 samples (43%) with normal expression for OPG. IL-6 expression was associated with MI, and all the genes were correlated with each other (p < 0.05). Multivariate Cox regression revealed an association of MI and perineural invasion with OS, and higher OS rate was associated with IL-6 downregulation (p = 0.053, 108.5 months).

Conclusions: Mandibular invasion may impact overall survival and is associated with IL-6 tumor expression. Downregulation of IL-6 by malignant cells is associated with higher overall survival.

查看原文本刊更多论文

口腔鳞状细胞癌中骨重塑相关基因表达：对下颌侵袭和总体生存的影响。

目的：口腔鳞状细胞癌（OSCC）的骨侵袭激活了RANK/RANKL/OPG和白细胞介素6 （IL-6）基因参与的骨重塑过程。本研究旨在评估RANK、RANKL、OPG和IL-6在与下颌侵袭（MI）相关的OSCC中的基因表达，并确定其对患者总生存期（OS）的影响。材料和方法：一项横断面研究选择了在参考中心接受下颌骨切除术治疗OSCC的患者，共220人。选取40例具有分子分析材料的年龄匹配患者进行RANK、RANKL、OPG和IL6表达分析，分为MI组（n=20）和无侵袭组（NI, n=20）。通过实时聚合酶链反应（由内源性GAPDH和非肿瘤RNA对照库校准）检测所选基因的肿瘤mRNA表达。结果：36例患者中有16例（44%）出现RANK下调；37例样本中有28例（75%）RANKL过表达；35个样本中有19个（54%）IL-6下调；37例样本中16例（43%）OPG表达正常。IL-6表达与心肌梗死相关，且各基因之间存在相关性(p结论：下颌侵袭可能影响总体生存，且与IL-6肿瘤表达相关。恶性细胞IL-6的下调与较高的总生存率相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Stomatology Oral and Maxillofacial Surgery Dentistry-Oral Surgery

CiteScore

2.20

自引率

9.10%

发文量

305

期刊介绍： J Stomatol Oral Maxillofac Surg publishes research papers and techniques - (guest) editorials, original articles, reviews, technical notes, case reports, images, letters to the editor, guidelines - dedicated to enhancing surgical expertise in all fields relevant to oral and maxillofacial surgery: from plastic and reconstructive surgery of the face, oral surgery and medicine, … to dentofacial and maxillofacial orthopedics. Original articles include clinical or laboratory investigations and clinical or equipment reports. Reviews include narrative reviews, systematic reviews and meta-analyses. All manuscripts submitted to the journal are subjected to peer review by international experts, and must: Be written in excellent English, clear and easy to understand, precise and concise; Bring new, interesting, valid information - and improve clinical care or guide future research; Be solely the work of the author(s) stated; Not have been previously published elsewhere and not be under consideration by another journal; Be in accordance with the journal''s Guide for Authors'' instructions: manuscripts that fail to comply with these rules may be returned to the authors without being reviewed. Under no circumstances does the journal guarantee publication before the editorial board makes its final decision. The journal is indexed in the main international databases and is accessible worldwide through the ScienceDirect and ClinicalKey Platforms.