Identification and Validation of Two Heterogeneous Molecular Subtypes and a Prognosis Predictive Model for Hepatocellular Carcinoma Based on Pyroptosis

Lai, Minshan; Liu, Qiang; Chen, Wenbo; Qi, Xuxin; Yang, Jianfeng; Jiang, Li; Yuan, Meng; Liu, Zhichun; He, Qiaojun; Cao, Ji; Yang, Bo

doi:10.1155/2022/8346816

Cited by 9 publications

(4 citation statements)

References 61 publications

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“…Interestingly, BAK expression was decreased in colorectal tumors and remained unchanged in most conditions [37], but increased BAK expression was strongly associated with a poor prognosis in patients with non-small cell lung cancer [38], which indicates that the role of BAK is unclear in different types of cancers. Consistent with our results, BAK1 has been identified as a prognostic gene in pyroptosis-related HCC and is associated with persistent hepatitis B virus infectionrelated HCC [39,40]. In this study, we found that the expression of BAK1 was upregulated in the high-risk group compared to the low-risk group.…”

Section: Discussionsupporting

confidence: 91%

Identification of Anoikis-Related Subgroups and Prognosis Model in Liver Hepatocellular Carcinoma

Chen

Huang

Ouyang

et al. 2023

IJMS

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Resistance to anoikis is a key characteristic of many cancer cells, promoting cell survival. However, the mechanism of anoikis in hepatocellular carcinoma (HCC) remains unknown. In this study, we applied differentially expressed overlapping anoikis-related genes to classify The Cancer Genome Atlas (TCGA) samples using an unsupervised cluster algorithm. Then, we employed weighted gene coexpression network analysis (WGCNA) to identify highly correlated genes and constructed a prognostic risk model based on univariate Cox proportional hazards regression. This model was validated using external datasets from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). Finally, we used a CIBERSORT algorithm to investigate the correlation between risk score and immune infiltration. Our results showed that the TCGA cohorts could be divided into two subgroups, with subgroup A having a lower survival probability. Five genes (BAK1, SPP1, BSG, PBK and DAP3) were identified as anoikis-related prognostic genes. Moreover, the prognostic risk model effectively predicted overall survival, which was validated using ICGC and GEO datasets. In addition, there was a strong correlation between infiltrating immune cells and prognostic genes and risk score. In conclusion, we identified anoikis-related subgroups and prognostic genes in HCC, which could be significant for understanding the molecular mechanisms and treatment of HCC.

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Section: Discussionsupporting

confidence: 91%

Identification of Anoikis-Related Subgroups and Prognosis Model in Liver Hepatocellular Carcinoma

Chen

Huang

Ouyang

et al. 2023

IJMS

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“…Furthermore, a novel ten-genebased signature was constructed by LASSO Cox regression to predict the OS of CCA. Because the heterogeneity among different patients has been widely reported to in uence the biological mechanisms, management, and pathological features of CCA patients 8 , constructing a prognostic biomarker with high precision and sensitivity as well as validation in an independent cohort is urgently needed to improve prognosis 35 . In our study, the prognostic signature was established and validated in several CCA transcriptome and proteome sequencing datasets with high sensitivity and accuracy.…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis-related genes establishment score system to assess the prognosis and immune microenvironment in cholangiocarcinoma

Liu

Zhu

Huang

et al. 2023

Preprint

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Background Cuproptosis is a novel type of mediated cell death strongly associated with the progression of several cancers and has been implicated as a potential therapeutic target. However, the role of cuproptosis in cholangiocarcinoma (CCA) for prognostic prediction, subgroup classification, and therapeutic strategies remains largely unknown. Methods A systematic analysis was conducted among 146 cuproptosis-related genes (CRGs) and clinical information based on independent mRNA and protein datasets to elucidate the potential mechanisms and prognostic prediction value of CRGs. A ten-CRG prediction model was constructed, and its effects on CCA prognosis were significantly connected to poor patient survival. Additionally, the expression patterns of our model included genes that were validated with several CCA cancer cell lines and a normal biliary epithelial cell line. Results First, a ten-CRG signature (ADAM9, ADAM17, ALB, AQP1, CDK1, MT2A, PAM, SOD3, STEAP3 and TMPRSS6) displayed excellent predictive performance for the overall survival of CCA. The low-cuproptosis group had a significantly better prognosis than the high-cuproptosis group with transcriptome and protein cohorts. Second, compared with the high-risk and low-risk groups, the two groups displayed distinct tumor microenvironments, reduced proportions of endothelial cells and increased levels of cancer-associated fibroblasts based on CIBERSORTx and EPIC analyses. Third, patients’ sensitivities to chemotherapeutic drugs and immune checkpoints revealed distinctive differences between the two groups. Finally, in replicating the expression patterns of the ten genes, these results were validated with qRT‒PCR results validating the abnormal expression pattern of the target genes in CCA. Conclusions Collectively, we established and verified an effective prognostic model that could separate CCA patients into two heterogeneous cuproptosis subtypes based on the molecular or protein characteristics of ten CRGs. These findings may provide potential benefits for unveiling molecular characteristics, and defining subgroups could improve the early diagnosis and individualized treatment of CCA patients.

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“…In a variety of clinical and translational studies, DHX9 was confirmed as a prognostic gene for cancers. Recently, Lai et al (17) reported that a total of 12 HCC-associated pyroptosis-related genes (HPRGs) including DHX9 were significantly related to poor survival, and a further five-gene risk model including DHX9 was established for prognostic prediction. As the same HCC, the DHX9-related gene prognostic model was established in gastric cancer and showed superior risk stratification (18).…”

Section: Discussionmentioning

confidence: 99%

The enigmatic helicase DHX9 as a candidate prognostic biomarker for resected pancreatic ductal adenocarcinoma

Chen

Cui

et al. 2022

Front. Oncol.

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BackgroundPancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, and current therapies have limited efficacy on PDAC. The DEAH-box helicase 9 (DHX9) is widely reported to influence cell biological behavior via regulating DNA replication, genomic stability, transcription, translation, and microRNA biogenesis. However, the prognostic role of DHX9 in PDAC remains unclear. Thus, the objective of this study is to investigate the prognostic value of DHX9 expression in PDAC patients.MethodsTumor specimens from PDAC patients with surgical resection were obtained, and DHX9 was stained and analyzed in this study. Univariate and multivariate Cox regression analyses were utilized to identify independent risk factors of overall survival (OS) and recurrence-free survival (RFS). The prognostic nomograms for predicting OS and RFS were established to obtain superior predictive power.ResultsAmong the enrolled 110 patients, 61 patients were identified as having high expression of DHX9. The correlation analysis revealed that higher DHX9 expression in PDAC was prone to have advanced N stage (p = 0.010) and TNM stage (p = 0.017). For survival, the median OS (21.0 vs. 42.0 months, p < 0.001) and RFS (12.0 vs. 24.0 months, p < 0.001) of patients in the high DHX9 group were significantly shorter than those in the low DHX9 group. Within the univariate and multivariate analyses, American Joint Committee on Cancer (AJCC) N stage (p = 0.036) and DHX9 expression (p = 0.041) were confirmed as independent prognostic factors of OS, while nerve invasion (p = 0.031) and DHX9 expression (p = 0.005) were independent prognostic factors of RFS. Finally, the novel prognostic nomograms for OS and RFS were established and showed superior predictive accuracy.ConclusionThis study identified the independent prognostic value of DHX9 for RFS and OS in resected PDAC patients, and higher DHX9 expression was prone to have an earlier recurrence and shorter OS. Therefore, DHX9 may be a promising and valuable biomarker and a potential target for treating PDAC. More accurate and promising predictive models would be achieved when DHX9 is incorporated into nomograms.

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Identification and Validation of Two Heterogeneous Molecular Subtypes and a Prognosis Predictive Model for Hepatocellular Carcinoma Based on Pyroptosis

Cited by 9 publications

References 61 publications

Identification of Anoikis-Related Subgroups and Prognosis Model in Liver Hepatocellular Carcinoma

Identification of Anoikis-Related Subgroups and Prognosis Model in Liver Hepatocellular Carcinoma

Cuproptosis-related genes establishment score system to assess the prognosis and immune microenvironment in cholangiocarcinoma

The enigmatic helicase DHX9 as a candidate prognostic biomarker for resected pancreatic ductal adenocarcinoma

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