Sivagnanam Ananthi, Shyamsundar Vidyarani, Kesavan Pallavi, Krishnamurthy Arvind, Thangaraj Soundara Viveka, Venugopal Divyambika Catakapatri, Kasirajan Hemashree, Ramani Pratibha, Sarma Vinutha Rachapudi, Ramshankar Vijayalakshmi
Department of Preventive Oncology (Research), Cancer Institute (WIA), Adyar, Chennai, 600020 Tamil Nadu, India.
Centre for Oral Cancer Prevention and Research, Sree Balaji Dental College and Hospital, Pallikaranai, Chennai, 600100 Tamil Nadu, India.
J Oncol. 2022 Apr 22;2022:4215097. doi: 10.1155/2022/4215097. eCollection 2022.
Oral tongue squamous cell carcinoma (OTSCC) is an aggressive cancer with high morbidity and mortality rates, despite multimodality management. There are currently no clinically relevant molecular markers that identify patients at higher risk of recurrence and failure. We undertook 2D-DIGE proteomic profiling to study the differentially expressed proteins in OTSCC evaluating their role in prognosis. 2D-DIGE coupled with tandem mass spectrometry was performed on tissues obtained from early staged OTSCC along with its paired apparently adjacent normal tissue samples ( = 10). Top upregulated protein was validated using immunohistochemistry ( = 345), comprising of retrospective early stage OTSCC ( = 150) and prospective series of oral precancers, normal, and oral cancers ( = 195). Saliva samples collected from oral cancer and precancer samples were analyzed by ELISA ( = 146). We found statistically significant differential expression in 151 proteins out of 700 proteins quantified. Top ten differentially regulated proteins were identified using mass spectrometry analysis. We found vimentin, the mesenchymal protein, to be the most upregulated protein in tongue tumor tissues compared to adjacent apparent normal tissues. Vimentin was found to be significantly overexpressed in oral precancers along with cancers compared to normal tissues. The vimentin expression correlated significantly with differentiated states of oral precancers and cancers. Vimentin was also detected at significantly higher levels in saliva collected from oral precancer and cancer patients compared to normal healthy volunteers. Validation of vimentin in an independent series of retrospective early staged OTSCC showed that the vimentin expression is significantly associated with treatment failures and poorer DFS. The vimentin expression is useful as both poor prognostic and early detection marker in oral cancer. Vimentin detection in saliva can be a diagnostic test to detect oral precancers that may have malignant potential, needing closer follow-up, and disease monitoring.
口腔舌鳞状细胞癌（OTSCC）是一种侵袭性癌症，尽管采用了多模式治疗，但其发病率和死亡率仍很高。目前尚无临床相关分子标志物可识别复发和治疗失败风险较高的患者。我们进行了二维差异凝胶电泳（2D-DIGE）蛋白质组分析，以研究OTSCC中差异表达的蛋白质，并评估它们在预后中的作用。对从早期OTSCC及其配对的明显相邻正常组织样本（n = 10）中获取的组织进行了二维差异凝胶电泳结合串联质谱分析。使用免疫组织化学（n = 345）对上调最明显的蛋白质进行验证，其中包括回顾性早期OTSCC（n = 150）以及口腔癌前病变、正常组织和口腔癌的前瞻性系列样本（n = 195）。通过酶联免疫吸附测定（ELISA）分析从口腔癌和癌前病变样本中收集的唾液样本（n = 146）。我们发现在定量的700种蛋白质中，有151种蛋白质存在统计学上显著的差异表达。通过质谱分析鉴定出上调最明显的十种差异调节蛋白质。我们发现，与相邻的明显正常组织相比，间充质蛋白波形蛋白是舌肿瘤组织中上调最明显的蛋白质。与正常组织相比，波形蛋白在口腔癌前病变和癌症中均显著过表达。波形蛋白的表达与口腔癌前病变和癌症的分化状态显著相关。与正常健康志愿者相比，从口腔癌前病变和癌症患者收集的唾液中波形蛋白的检测水平也显著更高。在独立的回顾性早期OTSCC系列中对波形蛋白进行验证表明，波形蛋白的表达与治疗失败和较差的无病生存期显著相关。波形蛋白的表达可作为口腔癌不良预后和早期检测的标志物。唾液中波形蛋白的检测可作为一种诊断测试，用于检测可能具有恶性潜能、需要密切随访和疾病监测的口腔癌前病变。
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