Role of PI3K-AKT-mTOR signaling pathway-related circular RNAs in the diagnosis and prognosis of hepatocellular carcinoma: a systematic review and meta-analysis

Abstract

Background Several studies have demonstrated that phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-related circular RNAs (circRNAs) play a role in the development and progression of hepatocellular carcinoma (HCC). However, a systematic review and meta-analysis of the role of PI3K/AKT-related circRNAs in the diagnosis and prognosis of HCC has not been reported at present. Herein, we systematically reviewed the literature and conducted a meta-analysis of the potential role of PI3K/AKT/mTOR-related circRNAs in the diagnosis and prognosis of HCC. Method PubMed, EMBASE, Cochrane Library, Web of Science, Scoups, Wanfang, Chinese Biomedical Literature Database (SinoMed), Chinese National Knowledge Infrastructure (CNKI) and Chinese Science and Technique Journals Database (VIP) databases were searched for relevant studies from inception to April 19, 2024. Pooled odds ratio (OR) was used to evaluate clinical case characteristics, sensitivity and specificity. Prognostic overall survival (OS) was estimated using the hazard ratio (HR). Subgroup analyses were conducted according to sample type, country and control group type. The quality of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool or the Newcastle-Ottawa Scale (NOS) method, and Egger’s tests were used to assess potential publication bias. STATA (version 17.0) software was used for statistical analysis. Results Twenty five eligible articles, including ten diagnostic studies and sixteen prognostic studies, involving 2995 HCC patients, 435 healthy controls and 338 controls with benign lesions were included in this meta-analysis. The pooled sensitivity and specificity were 0.80 (95% CI: 0.75–0.84) and 0.86 (95% CI: 0.77–0.92), respectively. Higher levels of PI3K/AKT/mTOR pathway-associated circRNAs are significantly associated with poor patient prognosis (OS:HR = 1.49, 95% Cl: 0.89–2.48, P < 0.001). Elevated levels of highly expressed circRNAs in patients were significantly associated with HbsAg positivity, MVI positivity, and worse TMN staging in patients with HCC, and elevated levels of low expressed circRNAs in patients were associated with MVI negativity in patients with HCC. No publication bias was found. Conclusion PI3K/AKT/mTOR-related circRNAs are potential biomarkers for HCC, especially in the diagnosis of HCC. Due to the small number of included articles and the limitation of the included population, more studies on the diagnostic and prognostic value of PI3K/AKT/mTOR pathway-related circRNAs are needed in the future.