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

Lab Med. 2023 Jul 5;54(4):411-423. doi: 10.1093/labmed/lmac125.

Abstract

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

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.

Keywords: biomarker; diagnosis; esophageal squamous cell carcinoma; logistic regression model; microRNA; next-generation sequencing.

MeSH terms

  • Case-Control Studies
  • Cell Line, Tumor
  • East Asian People
  • Esophageal Neoplasms* / diagnosis
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / diagnosis
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • MicroRNAs* / genetics
  • Retrospective Studies

Substances

  • MicroRNAs
  • MIRN363 microRNA, human
  • MIRN497 microRNA, human
  • phospholysine phosphohistidine inorganic pyrophosphate phosphatase, human