CircHIPK3 Promotes Growth and Metastasis of Colorectal Cancer

Background This systematic investigation evaluates the clinical significance of circular RNA circHIPK3 in colorectal cancer (CRC) pathogenesis and prognostic outcomes. Methods A dual-phase analytical approach was implemented: (1) Systematic literature retrieval (inception-January 2025) across Embase, Web of Science, and PubMed identified clinical studies comparing CRC outcomes by circHIPK3 expression levels. Quantitative synthesis of dichotomous variables was performed using odds ratios (ORs) with 95% confidence intervals (CI), whereas survival outcomes were analyzed through hazard ratios (HRs). (2) Independent validation utilizing gene expression omnibus (GEO) and the cancer genome atlas (TCGA) datasets examined circHIPK3 expression patterns and survival correlations, supplemented by pathway enrichment analysis for mechanistic insights. Results A total of two publications were identified in this analysis. The high circHIPK3 expression group exhibited significant differences in regional lymph node metastasis (OR = 0.09; 95% CI = 0.04 to 0.17; P ＜0.001, I 2 = 45%), local invasion (OR = 0.43; 95% CI = 0.24 to 0.77; P = 0.005, I 2 = 44%), and distant metastasis (OR = 0.18; 95% CI = 0.08 to 0.40; P ＜0.001, I 2 = 0%) compared to the low circHIPK3 expression group. Additionally, a significant correlation was established between high circHIPK3 expression and decreased overall survival (OS) in CRC patients (HR = 0.30, 95% CI = 0.16 to 0.56; P = 0.0002, I 2 = 0%). No statistically significant differences were noted in gender (OR = 0.84; 95% CI = 0.50 to 1.42; P = 0.51, I 2 = 0%), tumor location (OR = 0.60; 95% CI = 0.35 to 1.02; P = 0.06, I 2 = 0%), and differentiation (OR = 0.99; 95% CI = 0.53 to 1.86; P = 0.98, I 2 = 0%). Bioinformatics analyses based on GEO and TCGA data further indicated that high circHIPK3 mRNA or protein expression correlates with shorter survival probabilities. Additional biological function predictions suggest that circHIPK3 plays a role in the onset and progression of CRC through multiple signaling pathways. Conclusion Our integrative analysis identifies circHIPK3 overexpression as a multimodal prognostic biomarker in CRC, associated with aggressive metastatic behavior and reduced survival. The mechanistic linkage to oncogenic pathways suggests its potential as both a therapeutic target and risk stratification tool.