Identification of Tumor Suppressor Gene LHPP-Based 5-microRNA Signature That Predicts the Early- and Midstage Esophageal Squamous Cell Carcinoma: A Two-Stage Case-Control Study in the Chinese Han Population

鉴定基于肿瘤抑制基因 LHPP 的 5-microRNA 标记以预测早期和中期食管鳞状细胞癌:中国汉族人群的两阶段病例对照研究

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作者:Xiang Zhao, Xiaocun Zhu, Luoshai Wang, Yurao Chen, Ronghuai Chen, Zemao Zheng, Hengjin Yang, Wan Xia, Juan Yao, Kun Zhao

Conclusions

The prediction model has potential implications for diagnosis of early- and midstage ESCC.

Methods

The tumor suppressor gene phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)-based miRNA signature was identified using next-generation sequencing and 3 biological online prediction systems. This retrospective study established and validated an ESCC prediction model using a test cohort and a validation cohort.

Objective

To establish a novel approach for diagnosing early- and midstage esophageal squamous cell carcinoma (ESCC).

Results

Immunohistochemical staining and real-time quantitative polymerase chain reaction (RT-qPCR) results showed that LHPP protein levels were significantly lower in tissues with early- and midstage ESCC than in adjacent tissues (P < .01). Further, we confirmed that miR-15b-5p, miR-424-5p, miR-497-5p, miR-363-5p, and miR-195-5p inhibited LHPP. These 5 miRNAs were significantly elevated in the plasma of early- and midstage ESCC (P < .05). An ESCC prediction model combining these 5 miRNAs was established. Finally, in the external validation cohort, the model exhibited high discriminative value (sensitivity/specificity: 84.4%/93.3%). Conclusions: The prediction model has potential implications for diagnosis of early- and midstage ESCC.

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