Serum big endothelin-1 as a biomarker in oral squamous cell carcinoma patients: an analytical study

Detection of abnormally elevated levels of molecules in patients with oral cancer may be useful in early diagnosis. These markers can be included in current Histopathology grading and in TNM staging systems of Oral Squamous Cell Carcinoma (OSCC) to make it more efficient. Several pro-angiogenic molecules have been assessed for the same reason. Endothelin-1 (ET-1) is a vasoactive peptide associated with the development and spread of many solid tumors, including Squamous Cell Carcinoma (SCC), but its utility in OSCC has not been confirmed. Objective This study aims to evaluate the role of the serum big ET-1 as a biomarker of OSCC, by correlating it with the clinical staging and the histopathological grading. Material and Methods Serum levels of big ET-1 measured by the sandwich Enzyme-Linked Immunosorbent Assay (ELISA) in 40 OSCC cases were compared with the levels from the control group using independent t-test. Clinical stages and histopathological grades of OSCC cases were compared in relation to their mean levels of serum big ET-1, one using the Analysis of Variance (ANOVA) test and the other the independent t-test, respectively. The significance of the mean difference between the groups was evaluated by Tukey’s multiple comparison test. All statistical analyses were performed on GraphPad statistical software version 5.0. Results By comparing the mean of the big ET-1 concentrations of cases and controls, the independent t-test revealed significant higher big ET-1 concentration of OSCC cases when compared to controls (p<0.0001). Tukey’s multiple comparison test also revealed statistically significant difference among all OSCC stages in relation to the mean levels of serum big ET-1. However, the mean of the big ET-1 concentrations of cases of grade I and of grade II did not differ statistically (p=0.729). Conclusion Serum big ET-1 levels may be useful as a diagnostic tool in OSCC and as an adjunct to OSCC staging. However, its use as a prognostic marker warrants larger prospective studies.

检测口腔癌患者体内分子水平的异常升高，或可助力疾病早期诊断。此类生物标志物可纳入现有口腔鳞状细胞癌（Oral Squamous Cell Carcinoma, OSCC）的组织病理学分级与TNM分期体系，以提升其诊断效能。基于此研究目的，已有多种促血管生成分子被相关研究评估。内皮素-1（Endothelin-1, ET-1）是一种血管活性肽，与包括鳞状细胞癌（Squamous Cell Carcinoma, SCC）在内的多种实体肿瘤的发生与转移密切相关，但其在口腔鳞状细胞癌中的应用价值尚未得到证实。
**研究目的**：本研究旨在通过分析血清大内皮素-1（big ET-1）水平与口腔鳞状细胞癌临床分期及组织病理学分级的相关性，评估其作为OSCC生物标志物的应用价值。
**材料与方法**：本研究采用夹心酶联免疫吸附试验（Sandwich Enzyme-Linked Immunosorbent Assay, ELISA）检测40例OSCC患者的血清大内皮素-1水平，并以独立样本t检验与对照组的检测结果进行对比；分别采用方差分析（Analysis of Variance, ANOVA）与独立样本t检验，分析OSCC患者的临床分期、组织病理学分级与血清大内皮素-1平均水平的相关性；采用Tukey多重比较检验评估组间均值差异的显著性。所有统计学分析均通过GraphPad统计软件5.0版本完成。
**研究结果**：通过对比病例组与对照组的大内皮素-1平均浓度，独立样本t检验结果显示，OSCC患者的血清大内皮素-1浓度显著高于对照组（p<0.0001）；Tukey多重比较检验结果显示，不同OSCC临床分期患者的血清大内皮素-1平均水平均存在统计学差异；但Ⅰ级与Ⅱ级OSCC患者的血清大内皮素-1平均浓度无统计学差异（p=0.729）。
**研究结论**：血清大内皮素-1水平或可作为口腔鳞状细胞癌的诊断工具及分期辅助指标，但其作为预后标志物的应用价值仍需开展更大规模的前瞻性研究予以验证。