Identification of the PANoptosis‑Related Prognostic Gene Model and Characterization of Tumor Microenvironment Infiltration in HCC

Shi, Xinrui; Yang, Lei; Liu, Wenxuan; Gao, Xia; Tang, Xuejiao; Liu, Jiayi; Pan, Dongchen; Duan, Xueqing; Jin, Yuqing; Ren, Weiyan

doi:10.2139/ssrn.4267507

Cited by 2 publications

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“…The list of 274 PANoptosis-related genes (PRGs) was obtained from previous research which combined with the apoptosis, pyroptosis and necroptosis gene sets. 29 794 autophagy-related genes (ARGs) were obtained from the Autophagy Database (HAMdb), 30 (Supplementary Table 1).…”

Section: Data Sourcesmentioning

confidence: 99%

PANoptosis and Autophagy-Related Molecular Signature and Immune Landscape in Ulcerative Colitis: Integrated Analysis and Experimental Validation

Lu,

Li,

2024

JIR

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Background: Ulcerative colitis (UC) is an autoimmune inflammatory disorder of the gastrointestinal tract. Programmed cell death (PCD), including PANoptosis and autophagy, plays roles in inflammation and immunity. This study aimed to investigate the molecular signature and immune landscape of the PANoptosis-and autophagy-related differentially expressed genes (DEGs) in UC. Methods: Analyzing UC dataset GSE206285 yielded DEGs. Differentially expressed PANoptosis-and autophagy-related genes were identified using DEGs and relevant gene collections. Functional and pathway enrichment analyses were conducted. A protein-protein interaction (PPI) network was established to identify hub genes. TRRUST database predicted transcription factors (TFs), pivotal miRNAs, and drugs interacting with hub genes. Immune infiltration analysis, UC-associated single-cell sequencing data analysis, and construction of a competing endogenous RNA (ceRNA) network for hub genes were conducted. Machine learning identified key candidate genes, evaluated for diagnostic value via receiver operating characteristic (ROC) curves. A UC mice model verified expression of key candidate genes. Results: Identifying ten PANoptosis-related hub DEGs and four autophagy-related hub DEGs associated them with cell chemotaxis, wound healing and positive MAPK cascade regulation. Immune infiltration analysis revealed increased immunocyte infiltration in UC patients, with hub genes closely linked to various immune cell infiltrations. Machine learning identified five key candidate genes, TIMP1, TIMP2, TIMP3, IL6, and CCL2, with strong diagnostic performance. At the single-cell level, these genes exhibited high expression in inflammatory fibroblasts (IAFs). They showed significant expression differences in the colon mucosa of both UC patients and UC mice model. Conclusion:This study identified and validated novel molecular signatures associated with PANoptosis and autophagy in UC, potentially influencing immune dysregulation and wound healing, thus opening avenues for future research and therapeutic interventions.

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Section: Data Sourcesmentioning

confidence: 99%

PANoptosis and Autophagy-Related Molecular Signature and Immune Landscape in Ulcerative Colitis: Integrated Analysis and Experimental Validation

Lu,

Li,

2024

JIR

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“…Another validation dataset GSE16879 pro led microarray data of 48 in amed colonic mucosa and 6 normal colonic mucosa [24]. The list of 274 PANoptosis-related genes (PRGs) was obtained from previous research which combined with the apoptosis, pyroptosis and necroptosis gene sets [25]. 794 autophagy-related genes (ARGs) were obtained from the Autophagy Database (HAMdb) [26] (Table S1).…”

Section: Data Sourcesmentioning

confidence: 99%

Identification and validation of PANoptosis and autophagy-related molecular characterization in ulcerative colitis

Lu,

Li,

2023

Preprint

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Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. Programmed cell death (PCD), such as PANoptosis and autophagy, is involved in various inflammation- and immune-related diseases. This study aimed to examine the molecular signature and the associated immune cell infiltration of the PANoptosis- and autophagy-related differentially expressed genes (DEGs) in UC. Ten PANoptosis-related hub DEGs, including PDGFRB, TIMP1, MMP2, CD44, TIMP2, TGFB2, IL6, TIMP3, IL1B, HGF, and four autophagy-related hub DEGs, including CCL2, TGFB1, PPARG, and CXCR4, were identified. These hub genes were associated with cell chemotaxis, wound healing and positive regulation of MAPK cascade. Immune infiltration analysis revealed UC patients exhibited a higher infiltration of immunocytes and these hub genes were closely related to a various of immune cell infiltrations. Through the machine learning algorithms, five key candidate genes, TIMP1, TIMP2, TIMP3, IL6, and CCL2, showed a good diagnostic performance in distinguishing UC patients from healthy individuals. Furthermore, these five key candidate genes were highly expressed in inflammatory fibroblasts (IAFs) by single-cell sequencing analysis. The expression levels of the key candidate genes exhibited significant differences in the colon mucosa of UC patients. Our findings indicated that PANoptosis and autophagy or crosstalk between them might be implicated in immune dysregulation and wound healing in UC via regulating specific immune cells or IAFs and interacting with key signals such as cell chemotaxis and MAPK signaling pathways.

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Identification of the PANoptosis‑Related Prognostic Gene Model and Characterization of Tumor Microenvironment Infiltration in HCC

Cited by 2 publications

References 0 publications

PANoptosis and Autophagy-Related Molecular Signature and Immune Landscape in Ulcerative Colitis: Integrated Analysis and Experimental Validation

PANoptosis and Autophagy-Related Molecular Signature and Immune Landscape in Ulcerative Colitis: Integrated Analysis and Experimental Validation

Identification and validation of PANoptosis and autophagy-related molecular characterization in ulcerative colitis

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