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鉴定血浆 hsa_circ_0000190 和 0001649 作为预测口腔鳞状细胞癌患者复发和治疗反应的生物标志物。

Identification of plasma hsa_circ_0000190 and 0001649 as biomarkers for predicting the recurrence and treatment response of patients with oral squamous cell carcinoma.

机构信息

Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Department of Dentistry, School of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.

出版信息

J Chin Med Assoc. 2022 Apr 1;85(4):431-437. doi: 10.1097/JCMA.0000000000000700.

Abstract

BACKGROUND

Oral squamous cell carcinoma (OSCC) is a type of malignancy characterized by high relapse and recurrence rates in the late stage despite optimal surgical intervention and postoperative chemoradiotherapy. Because the management of relapse following definitive treatment is challenging, accurate risk stratification is of clinical significance to improve treatment outcomes. Circular RNAs (circRNAs) are noncoding RNAs featured with cell-type specificity and high stability, owing to their circular structure, making these molecules excellent biomarkers for a variety of diseases.

METHODS

The levels of hsa_circ_0000190 and 0001649 in plasma samples from 30 healthy controls and 66 OSCC patients were determined by droplet digital polymerase chain reaction. The same primer sets were used with PCR to examine the expression of these two circRNAs in cancerous and adjacent normal tissues. A receiver operating characteristics curve was generated to evaluate the diagnostic value. The Kaplan-Meier method with a log-rank test was used for survival analysis.

RESULTS

We identified two circRNAs as potential biomarkers for OSCC, showing that the plasma level of hsa_circ_0000190 was significantly decreased in the late stage and marginally correlated with the development of second primary OSCC. We also found that the decreased plasma hsa_circ_0001649 was correlated with the recurrence and poor prognosis of patients. Additionally, we found that high plasma hsa_circ_0000190, but not hsa_circ_0001649, possibly predicted a better response of patients to induction chemotherapy.

CONCLUSION

Our study demonstrated the potential of biomarkers in plasma to inform not just the tumor but the entire oral cavity, thereby offering a prediction for early recurrence and second primary OSCC. The plasma circRNAs remain valuable for OSCC, albeit the easy accessibility to the oral cavity.

摘要

背景

口腔鳞状细胞癌(OSCC)是一种恶性肿瘤,尽管进行了最佳的手术干预和术后放化疗,但在晚期仍有较高的复发和转移率。由于对确定性治疗后的复发进行管理具有挑战性,因此准确的风险分层对于改善治疗结果具有临床意义。环状 RNA(circRNA)是一类具有细胞特异性和高稳定性的非编码 RNA,由于其环状结构,使这些分子成为各种疾病的优秀生物标志物。

方法

通过液滴数字聚合酶链反应(PCR)确定 30 名健康对照者和 66 名 OSCC 患者的血浆样本中 hsa_circ_0000190 和 0001649 的水平。使用相同的引物进行 PCR 检测,以检测这两种 circRNA 在癌组织和相邻正常组织中的表达。生成接受者操作特征曲线以评估诊断价值。使用 Kaplan-Meier 方法和对数秩检验进行生存分析。

结果

我们确定了两种 circRNA 作为 OSCC 的潜在生物标志物,表明 hsa_circ_0000190 的血浆水平在晚期显著降低,并且与第二原发 OSCC 的发展有轻微相关性。我们还发现,血浆 hsa_circ_0001649 的降低与患者的复发和预后不良有关。此外,我们发现高血浆 hsa_circ_0000190,而不是 hsa_circ_0001649,可能预测患者对诱导化疗的反应更好。

结论

我们的研究表明,血浆生物标志物不仅可以提供肿瘤信息,还可以提供整个口腔的信息,从而对早期复发和第二原发 OSCC 进行预测。尽管口腔易于获得,但血浆 circRNA 对 OSCC 仍然具有价值。

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