HECW1 Gene's Role in Gastric Cancer Prognosis and Its Suppressive Effect on Cell Progression after Knockdown.

Abstract

Background: The HECT, C2, and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) gene is a member of the HECT family of E3 ubiquitin ligases. While HECW1 has been implicated in various cancers, its role in gastric cancer (GC) remains unclear.

Methods: Bioinformatics approaches were employed to investigate HECW1's role in GC. Functional assays, including the CCK-8, transwell migration, and wound healing assays, were performed to assess its impact on GC cell proliferation, invasion, and migration.

Results: HECW1 expression was significantly upregulated in GC tissues compared to normal controls, correlating with specific clinical characteristics. Cox regression analyses identified HECW1 as an independent prognostic factor for GC. Prognostic nomograms accurately predicted 1-, 3-, and 5-year survival rates, with calibration curves closely aligned with the ideal diagonal line. Elevated HECW1 expression was associated with poorer overall survival and disease progression outcomes. ROC analyses demonstrated that HECW1 had strong predictive power for outcomes (AUC = 0.746, CI = 0.683-0.808) and five-year survival rates (AUC = 0.734, CI = 0.600-0.869). Enrichment analysis suggested HECW1's involvement in protein processing and interactions with substrates such as SMAD4, TTF1, DVL1, and NEDD4. Functional assays showed that HECW1 knockdown significantly reduced GC cell proliferation, invasion, and migration.

Conclusions: HECW1 acts as an oncogene in GC and represents a potential prognostic indicator. Targeting HECW1 may inhibit GC progression, providing a promising therapeutic strategy.