Research progress on molecular markers related to diagnosis and prognosis and anti-hepatocellular carcinoma signaling pathways

Abstract Objective Hepatocellular carcinoma (HCC) boasts high global incidence and mortality. Severe HBV infection and prevalent non-alcoholic steatohepatitis (NASH) lead to a heavy HCC disease burden in China. HCC has occult early symptoms, and most patients are diagnosed at advanced stages with high postoperative recurrence risk. Traditional imaging and serological markers fail to achieve accurate early diagnosis and identify residual tumors, unable to meet the clinical needs of precise and individualized HCC treatment. This study systematically reviewed HCC diagnostic and prognostic molecular markers, analyzed the defects of traditional markers, illustrated the mechanisms and clinical efficacy of novel markers, sorted out anti-HCC core signaling pathways, and explored multi-marker combined strategies to support precise HCC diagnosis and treatment. Methods We integrated up-to-date domestic and international omics data, cellular and animal experimental verification results, and clinical evidence. This study analyzed the clinical and molecular deficiencies of traditional serological markers, clarified the expression features, regulatory pathways and translational potential of novel molecular markers, explored abnormal mechanisms and drug targets of key HCC signaling pathways, and established an optimization and evaluation system for multi-marker combined detection. Result Traditional HCC molecular markers have poor sensitivity and specificity, and cannot distinguish postoperative tissue repair from residual tumors, with weak correlation with HCC biological behaviors. Novel markers including oncogene (Onc) and tumor suppressor genes (TSGs), non-coding RNAs, translation initiation- and protein homeostasis-related genes and metabolic reprogramming-related genes are abnormally expressed in HCC. They regulate tumor proliferation, apoptosis, invasion and metastasis, improving early diagnosis, prognostic stratification and recurrence warning. Multi-marker combination compensates for single detection defects, and pathway-targeted drugs optimize the accuracy of HCC prognosis and individualized treatment formulation. Conclusion With the advantages of non-invasive detection and dynamic reflection of tumor characteristics, molecular markers combined with pathway-targeted therapy can break the bottlenecks of traditional HCC diagnosis and treatment. The synergism of traditional and novel markers, multi-marker joint detection and targeted therapy has great clinical translational value, providing a new direction for realizing precise diagnosis, prognosis and individualized treatment of HCC. The summarized mechanisms and strategies can support the clinical practice of HCC precision medicine.