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Identification of PANoptosis-related subtypes, construction of a prognosis signature, and tumor microenvironment landscape of hepatocellular carcinoma using bioinformatic analysis and experimental verification.
Ouyang, Guoqing; Li, Qiuyun; Wei, Yangnian; Dai, Wenbin; Deng, Haojian; Liu, Youli; Li, Jiaguang; Li, Mingjuan; Luo, Shunwen; Li, Shuang; Liang, Yunying; Pan, Guandong; Yang, Jianqing; Gan, Tao.
Afiliação
  • Ouyang G; Department of General Surgery, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
  • Li Q; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi, China.
  • Wei Y; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China.
  • Dai W; Liuzhou Hepatobiliary and Pancreatic Diseases Precision Diagnosis Research Center of Engineering Technology, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
  • Deng H; Department of General Surgery, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
  • Liu Y; Liuzhou Hepatobiliary and Pancreatic Diseases Precision Diagnosis Research Center of Engineering Technology, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
  • Li J; Department of Hepatobiliary Surgery, Ruikang Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
  • Li M; Department of Pathology, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
  • Luo S; Department of Emergency Medical, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
  • Li S; Department of Pathology, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
  • Liang Y; Department of Pathology, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
  • Pan G; Department of General Surgery, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
  • Yang J; Department of General Surgery, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
  • Gan T; Department of General Surgery, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China.
Front Immunol ; 15: 1323199, 2024.
Article em En | MEDLINE | ID: mdl-38742112
ABSTRACT

Background:

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. PANoptosis is a recently unveiled programmed cell death pathway, Nonetheless, the precise implications of PANoptosis within the context of HCC remain incompletely elucidated.

Methods:

We conducted a comprehensive bioinformatics analysis to evaluate both the expression and mutation patterns of PANoptosis-related genes (PRGs). We categorized HCC into two clusters and identified differentially expressed PANoptosis-related genes (DEPRGs). Next, a PANoptosis risk model was constructed using LASSO and multivariate Cox regression analyses. The relationship between PRGs, risk genes, the risk model, and the immune microenvironment was studies. In addition, drug sensitivity between high- and low-risk groups was examined. The expression profiles of these four risk genes were elucidate by qRT-PCR or immunohistochemical (IHC). Furthermore, the effect of CTSC knock down on HCC cell behavior was verified using in vitro experiments.

Results:

We constructed a prognostic signature of four DEPRGs (CTSC, CDCA8, G6PD, and CXCL9). Receiver operating characteristic curve analyses underscored the superior prognostic capacity of this signature in assessing the outcomes of HCC patients. Subsequently, patients were stratified based on their risk scores, which revealed that the low-risk group had better prognosis than those in the high-risk group. High-risk group displayed a lower Stromal Score, Immune Score, ESTIMATE score, and higher cancer stem cell content, tumor mutation burden (TMB) values. Furthermore, a correlation was noted between the risk model and the sensitivity to 56 chemotherapeutic agents, as well as immunotherapy efficacy, in patient with. These findings provide valuable guidance for personalized clinical treatment strategies. The qRT-PCR analysis revealed that upregulated expression of CTSC, CDCA8, and G6PD, whereas downregulated expression of CXCL9 in HCC compared with adjacent tumor tissue and normal liver cell lines. The knockdown of CTSC significantly reduced both HCC cell proliferation and migration.

Conclusion:

Our study underscores the promise of PANoptosis-based molecular clustering and prognostic signatures in predicting patient survival and discerning the intricacies of the tumor microenvironment within the context of HCC. These insights hold the potential to advance our comprehension of the therapeutic contribution of PANoptosis plays in HCC and pave the way for generating more efficacious treatment strategies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Carcinoma Hepatocelular / Biologia Computacional / Microambiente Tumoral / Neoplasias Hepáticas Limite: Female / Humans / Male Idioma: En Revista: Front Immunol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Carcinoma Hepatocelular / Biologia Computacional / Microambiente Tumoral / Neoplasias Hepáticas Limite: Female / Humans / Male Idioma: En Revista: Front Immunol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Suíça