口腔鳞状细胞癌患者唾液microRNA-342 和 Naa10p 表达与颈淋巴结隐匿性转移的关系

Correlation between salivary microRNA-342 and Naa10p and occult lymph node metastasis in oral squamous cell carcinoma

摘要:

目的 检测口腔鳞状细胞癌（OSCC）患者唾液中microRNA-342（miR-342）和Naa10p 的表 达与颈淋巴结隐匿性转移的关系。方法 选取2017 年5 月—2019 年12 月浙江大学医学院附属杭州市第一人 民医院接受原发灶扩大切除术及颈部淋巴结清扫术的cN0 OSCC 患者85 例，术前收集患者漱口后未经刺激 的唾液标本。另外收集30 例口腔黏膜癌前病变患者和30 例健康志愿者的唾液标本。分别采用qRT-PCR 和 ELISA 法检测miR-342 和Naa10p 蛋白。结果 癌前病变组和OSCC 组唾液miR-342 水平较对照组降低， Naa10p 水平较对照组升高（P <0.05）。另外，OSCC 组唾液中miR-342 表达较癌前病变组降低，Naa10p 水平 较癌前病变组升高（P <0.05）。经Pearson 相关性分析，OSCC 患者唾液miR-342 与Naa10p 呈负相关（r =-0.693， P <0.05）。不同肿瘤生长方式、肿瘤直径及是否发生颈淋巴结隐匿性转移的OSCC 患者唾液miR-342 表达、 Naa10p 水平比较，差异有统计学意义（P <0.05）。唾液miR-342 和Naa10p 诊断OSCC 患者颈淋巴结隐匿 性转移的截断值分别为0.595、386.10 pg/ml，敏感性分别为80.00%（95% CI ：0.670，0.888）和78.00%（95% CI ：0.648，0.872），特异性分别为54.29%（95% CI ：0.382，0.695）和42.86%（95% CI ：0.280，0.571），AUC 分 别为0.720（95% CI ：0.614，0.827）和0.662（95% CI ：0.546，0.778），唾液miR-342 对颈淋巴结隐匿性转移 的诊断效能高于唾液Naa10p（P <0.05）。结论 OSCC 患者唾液miR-342 表达降低，Naa10p 水平升高，两者 呈负相关，有望成为判断颈淋巴结隐匿性转移的重要指标。

Abstract:

Objective To detect the expression of salivary miR-342 and N-α-acetyltransferase 10 protein (Naa10p) in oral squamous cell carcinoma (OSCC) and their correlation with occult lymph node metastasis. Methods The saliva samples were taken from 85 cN0 OSCC patients treated with extended resection of primary foci and neck lymphadenectomy from May 2017 to December 2019. Additionally, 30 patients with oral precancerous lesions and 30 healthy volunteers were also enrolled. The unstimulated saliva samples were swabbed after rinsing the mouth. The qRT-PCR and ELISA method were respectively performed to detect the expressions of miR-342 and Naa10p protein in saliva samples. Results Compared to that in patients with oral precancerous lesions and healthy subjects, the salivary miR-342 expression in OSCC patients was lower [(0.75±0.25) VS (2.75±0.62) VS (1.00±0.09)], while Naa10p protein level was higher [(299.67±156.83) pg/ml VS (118.54±57.69) pg/ml VS (55.84±18.17) pg/ml] (P < 0.05). Salivary miR-342 in OSCC patients was negatively related with Naa10p (r = -0.693, P = 0.000) as indicated by Pearson analysis. The expressions of miR-342 and Naa10p were associated with tumor growth pattern and size of lesions and occult lymph node metastasis (P < 0.05). ROC analysis showed that salivary miR-342 [AUC=0.720 (95% CI: 0.614, 0.827)] and Naa10p [AUC=0.662 (95% CI: 0.546, 0.778)] would be the potential markers for diagnosis of occult lymph node metastasis (Z = 7.145, P < 0.05). Salivary Naa10p > 386.10 pg/ml [Ol^R=0.630 (95% CI: 0.514, 0.817)] would be the independent risk factor of occult lymph node metastasis, while miR-342≥0.595 [Ol^R=2.759 (95% CI: 1.295, 3.621)] would be the independent protective factor (P < 0.05). Conclusions Salivary miR-342 expression is decreased while Naa10p level is increased in OSCC patients. Besides, miR-342 and Naa10p are negatively related, and would be the potential diagnostic factors for occult lymph node metastasis in OSCC patients.