PD‐1/PD‐L1 in Hepatocellular Carcinoma (2014–2024): A Combined Macro and Micro Analysis of Immunotherapy Implications

ABSTRACT Hepatocellular carcinoma (HCC) represents a significant global health issue, with the PD‐1/PD‐L1 axis serving a pivotal target for immunotherapy in this malignancy. However, a comprehensive bibliometric analysis of PD‐1/PD‐L1 research in HCC is lacking. This study therefore aims to map the research landscape and identify prognostic biomarkers associated with PD‐1/PD‐L1 therapies in HCC. We conducted a bibliometric analysis of 1817 relevant articles published between 2014 and 2024, retrieved from the Web of Science Core Collection. Knowledge mapping was performed using CiteSpace and VOSviewer. Additionally, three bulk RNA datasets from the GEO database were analyzed through differential gene expression, weighted gene co‐expression network analysis (WGCNA), and machine learning algorithms to identify core genes related to PD‐1/PD‐L1 therapy. Our results indicate a steady increase in research output, with a marked surge after 2020. Leading institutions, particularly in China, such as Sun Yat‐sen University and Fudan University, were found to be the dominant contributors. Keyword analysis revealed an evolutionary trajectory of research focus, shifting from basic science to clinical applications and, more recently, to combination therapies. Bioinformatics analysis identified AVPR1A as a core gene, demonstrating high diagnostic potential for predicting patient responses to PD‐1/PD‐L1 therapies. In summary, this study…This study provides a bibliometric and bioinformatics analysis of PD‐1/PD‐L1 in HCC, highlighting research trends and the promise of combination therapies. The identification of key genes offers new insights into therapeutic mechanisms and propose potential targets for future research and clinical applications.