Wong Yin-Ling, Ramanathan Anand, Yuen Kar Mun, Mustafa Wan Mahadzir Wan, Abraham Mannil Thomas, Tay Keng Kiong, Rahman Zainal Ariff Abdul, Chen Yeng
Department of Oral & Craniofacial Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
PeerJ. 2021 Jun 10;9:e11548. doi: 10.7717/peerj.11548. eCollection 2021.
Oral squamous cell carcinoma (OSCC) has increased in incidence from 1990 to 2017, especially in South and Southeast Asia. It is often diagnosed at an advanced stage with a poor prognosis. Therefore, early detection of OSCC is essential to improve the prognosis of OSCC. This study aims to identify the differentially expressed serum proteins as potential biomarkers for oral squamous cell carcinoma (OSCC).
Comparative proteomics profiling of serum samples from OSCC patients, oral potentially malignant disorder (OPMD) patients, and healthy individuals were performed using two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS) ( = 60) and bioinformatics analysis. The enzyme-linked immunosorbent assay (ELISA) ( = 120) and immunohistochemistry (IHC) ( = 70) were used to confirm our findings.
The 2-DE analysis revealed that 20 differentially expressed proteins were detected in OPMD and OSCC ( < 0.05). Bioinformatics analysis indicated that the activation of classical complement, liver X receptor/retinoid X receptor (LXR/RXR) activation, and acute phase response signaling pathway are associated with the development and progression of OSCC. Most of the detected proteins are acute-phase proteins and were related to inflammation and immune responses, including apolipoprotein A-I (APOA1), complement C3 (C3), clusterin (CLU), and haptoglobin (HP). The expression levels of CLU and HP in ELISA are consistent with the findings from the 2-DE analysis, except for the mean serum level of HP in OPMD, whereby it was slightly higher than that in control. IHC results demonstrated that CLU and HP are significantly decreased in OSCC tissues.
Decreased expression of CLU and HP could serve as complementary biomarkers of OSCC. These proteins may assist in predicting the outcomes of OSCC patients. However, a larger cohort is needed for further investigation.
从1990年到2017年，口腔鳞状细胞癌（OSCC）的发病率有所上升，尤其是在南亚和东南亚地区。它通常在晚期被诊断出来，预后较差。因此，早期发现OSCC对于改善其预后至关重要。本研究旨在鉴定差异表达的血清蛋白，作为口腔鳞状细胞癌（OSCC）的潜在生物标志物。
使用二维凝胶电泳（2-DE）结合质谱（MS）（n = 60）和生物信息学分析，对OSCC患者、口腔潜在恶性疾病（OPMD）患者和健康个体的血清样本进行比较蛋白质组学分析。采用酶联免疫吸附测定（ELISA）（n = 120）和免疫组织化学（IHC）（n = 70）来证实我们的发现。
二维凝胶电泳分析显示，在OPMD和OSCC中检测到20种差异表达的蛋白质（P < 0.05）。生物信息学分析表明，经典补体激活、肝X受体/视黄酸X受体（LXR/RXR）激活和急性期反应信号通路与OSCC的发生和发展有关。大多数检测到的蛋白质是急性期蛋白，与炎症和免疫反应相关，包括载脂蛋白A-I（APOA1）、补体C3（C3）、簇集素（CLU）和触珠蛋白（HP）。ELISA中CLU和HP的表达水平与二维凝胶电泳分析结果一致，但OPMD中HP的平均血清水平略高于对照组。免疫组织化学结果表明，OSCC组织中CLU和HP显著降低。
CLU和HP表达降低可作为OSCC的补充生物标志物。这些蛋白质可能有助于预测OSCC患者的预后。然而，需要更大的队列进行进一步研究。
