The liquid biopsy has gained significant attention in cancer diagnostics, with circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) being recognized as key biomarkers for tumor detection and monitoring. However, each biomarker possesses inherent limitations that restrict its standalone clinical utility, such as the rarity and heterogeneity of CTCs and the variable sensitivity and specificity of ctDNA assays. This highlights the necessity of integrating both biomarkers to maximize diagnostic and prognostic potential, offering a more comprehensive understanding of the tumor biology and therapeutic response. In this review, we summarize clinical studies that have explored the combined analysis of CTCs and ctDNA as biomarkers, providing insights into their synergistic value in diverse tumor types. Specifically, this paper examines the individual advantages and limitations of CTCs and ctDNA, details the findings of combined biomarker studies across various cancers, highlights the benefits of dual biomarker approaches over single-biomarker strategies, and discusses future prospects for advancing personalized oncology through liquid biopsies. By offering a comprehensive overview of clinical studies combining CTCs and ctDNA, this review serves as a guideline for researchers and clinicians aiming to enhance biomarker-based strategies in oncology and informs biosensor design for improved biomarker detection.

Hepatocellular carcinoma (HCC) is a highly aggressive form of liver cancer with poor prognosis. The lack of reliable biomarkers for early detection and accurate diagnosis and prognosis poses a significant challenge to its effective clinical management. In this study, we investigated the diagnostic and prognostic potential of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in peripheral blood mononuclear cells (PBMCs) in HCC. PD-1 and CTLA-4 gene expression was analyzed comparatively using PBMCs collected from HCC patients and healthy individuals. The results revealed higher PD-1 gene expression levels in patients with multifocal tumors, lymphatic invasion, or distant metastasis than those in their control counterparts. However, conventional serum biomarkers of liver function do not exhibit similar correlations. In conclusion, PD-1 gene expression is associated with OS and PFS and CTLA-4 gene expression is associated with OS, whereas the serum biomarkers analyzed in this study show no significant correlation with survival in HCC. Hence, PD-1 and CTLA-4 expressed in PBMCs are considered potential prognostic biomarkers for patients with HCC that can facilitate prediction of malignancy, response to currently available HCC treatments, and overall survival.