PANoptosis-based molecular subtyping and HPAN-index predicts therapeutic response and survival in hepatocellular carcinoma

Abstract

BackgroundHepatocellular carcinoma (HCC) is a highly prevalent and fatal cancer. The role of PANoptosis, a novel form of programmed cell death, in HCC is yet to be fully understood. This study focuses on identifying and analyzing PANoptosis-associated differentially expressed genes in HCC (HPAN_DEGs), aiming to enhance our understanding of HCC pathogenesis and potential treatment strategies.MethodsWe analyzed HCC differentially expressed genes from TCGA and IGCG databases and mapped them to the PANoptosis gene set, identifying 69 HPAN_DEGs. These genes underwent enrichment analyses, and consensus clustering analysis was used to determine three distinct HCC subgroups based on their expression profiles. The immune characteristics and mutation landscape of these subgroups were evaluated, and drug sensitivity was predicted using the HPAN-index and relevant databases.ResultsThe HPAN_DEGs were mainly enriched in pathways associated with the cell cycle, DNA damage, Drug metabolism, Cytokines, and Immune receptors. We identified three HCC subtypes (Cluster_1, SFN+PDK4-; Cluster_2, SFN-PDK4+; Cluster_3, SFN/PDK4 intermediate expression) based on the expression profiles of the 69 HPAN_DEGs. These subtypes exhibited distinct clinical outcomes, immune characteristics, and mutation landscapes. The HPAN-index, generated by machine learning using the expression levels of 69 HPAN_DEGs, was identified as an independent prognostic factor for HCC. Moreover, the high HPAN-index group exhibited a high response to immunotherapy, while the low HPAN-index group showed sensitivity to small molecule targeted drugs. Notably, we observed that the YWHAB gene plays a significant role in Sorafenib resistance.ConclusionThis study identified 69 HPAN_DEGs crucial to tumor growth, immune infiltration, and drug resistance in HCC. Additionally, we discovered three distinct HCC subtypes and constructed an HPAN-index to predict immunotherapeutic response and drug sensitivity. Our findings underscore the role of YWHAB in Sorafenib resistance, presenting valuable insights for personalized therapeutic strategy development in HCC.

Identification and Analysis of PANoptosis-Related Genes in Sepsis-Induced Lung Injury by Bioinformatics and Experimental Verification

“…Meanwhile, 277 PANoptosis-related genes were identified from the published literature by merging the gene lists of apoptosis, necroptosis and pyroptosis while removing redundant genes. 16 Finally, DEGs were intersected with PANoptosis-related genes to obtain SPAN_DEGs.…”

A novel PANoptosis-related long non-coding RNA index to predict prognosis, immune microenvironment and personalised treatment in hepatocellular carcinoma

“…An increasing number of studies have reported a role for PANoptosis in the malignant biological behaviour and evolution of cancer and on the influence on tumour responses to immunotherapy [ 11 – 13 ]. Additionally, recent studies have demonstrated that PANoptosis-based molecular subtyping is helpful in determining the prognosis and therapeutic response of HCC [ 14 , 15 ], providing a basis for individualised precision therapy [ 16 ]. Hence, the exploration of the molecular mechanisms of PANoptosis in HCC has implications for broadening the diagnostic and therapeutic options presented for HCC.…”

Multidimensional Analysis of PANoptosis-Related Molecule CASP8: Prognostic Significance, Immune Microenvironment Effect, and Therapeutic Implications in Hepatocellular Carcinoma

“…In addition, understanding the unique mechanisms of PANoptosis in HCC is vital for predicting treatment responses and developing personalized treatment plans. Given the central role of PANoptosis in the pathogenesis of HCC, in-depth research in this area is crucial for the development of new diagnostic biomarkers and therapeutic targets [14]. Tis will not only help elucidate the pathophysiological mechanisms of HCC but may also lead to more efective treatment modalities, thereby improving clinical outcomes for patients.…”