ctDNA carries the gene mutation information of all tumour cells, which can be detected in the early stages of tumour development. Tumour cells can release nucleic acid fragments into the circulation, which become circulating tumour DNA (ctDNA), and this may be considered a new generation of tumour molecular markers. With the development of genetic technology, scholars have attempted to predict the occurrence of disease and prognostic assessment from a genetic perspective. However, the heterogeneity of serum inflammatory markers can make their applicability questionable. Recent studies have found that systemic inflammatory responses are closely associated with tumour development, such as the neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, which have been shown to correlate with the prognosis of a variety of malignancies. Therefore, there is an urgent need for specific and sensitive serological markers for effective early detection and postoperative recurrence monitoring, as well as effective measures to prevent HCC metastasis and recurrence. According to statistics, the 5-year recurrence rate after HCC resection is as high as 70%, and blood metastasis is the most common. In addition, microvascular invasion and distant metastasis can occur in the early stage of HCC, and the postoperative recurrence and metastasis rates of patients are extremely high. Because the early clinical manifestations of HCC patients are not clear, the symptoms are hidden, and there is a lack of specific and sensitive early diagnostics, most patients are in the middle and late stages of diagnosis and miss the opportunity for radical resection. Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Mutations in the TERT and SOCS3 promoters in ctDNA are associated with poor prognosis and are expected to become good targets for liquid biopsy and to help select treatment strategies. The evidence provided by this analysis suggests that ctDNA may be a prognostic biomarker and is negatively correlated with the survival of HCC patients.
The univariate and multivariate descriptive analysis results showed that ctDNA was related to shorter DFS, and the effect sizes were HR = 3.28, 95% CI (1.23, 11.30), HR = 3.01, 95% CI (1.11, 10.5). The combined results of multivariate analysis showed that ctDNA was related to a shorter risk of OS (HR = 3.74, 95% CI (1.45, 9.65), ). The univariate analysis results showed that ctDNA was related to poor OS (HR = 4.48, 95% CI (1.17, 13.70), ). The results of survival curve analysis showed that ctDNA was related to poor OS and DFS, and the effect sizes were HR = 2.44, 95% CI (1.42, 4.20), HR = 2.63, 95% CI (1.96, 3.53). In total, 8 articles were included, encompassing 577 HCC patients.
The hazard ratio (HR) was used to combine the survivorship curve and univariate and multivariate results of the included studies. We evaluated the quality and design of these studies. The PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases were searched to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to January 2022. We conducted a systematic review of published research data to evaluate the prognostic value of ctDNA in HCC patients. Circulating tumour DNA (ctDNA) is a noninvasive method of detecting tumours, and its prognostic significance in hepatocellular carcinoma (HCC) patients is controversial.