A novel DNA methylation‐driver gene signature for long‐term survival prediction of hepatitis‐positive hepatocellular carcinoma patients

Fu, Jie; Qin, Wei; Tong, Qing; Li, Zhenghao; Shao, Yaoli; Liu, Zhiqiang; Li, Chun; Wang, Zicheng; Xu, Xundi

doi:10.1002/cam4.4838

Cited by 4 publications

(5 citation statements)

References 66 publications

(127 reference statements)

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“…Moreover, MAPK12 can also in uence the risk and survival of patients with colorectal cancer by modulating the MAPK signaling pathway [23,24]. F2RL2 has been reported to be a prognostic marker for glioma and breast cancer [25]. C8G plays a critical role in endothelial responses to in ammation and has potential utility as an S1PR2 inhibitor in treating in ammation [26].…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Coagulation Factor-Related Prognostic Model for Colorectal Cancer Based on the Public Database

Han

et al. 2023

Preprint

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Background:Colorectal cancer is one of the most common malignant cancers in the world, which is a serious threat to human health with increasingly diagnosed cases every year.It has been reported that coagulation factors play an important role in various cancer. However, the role of coagulation factor-related genes in colorectal cancer remains unknown. Methods: Gene expression data with clinical information of colorectal cancer samples were downloaded from the TCGA (The Cancer Genome Atlas) database and Gene Expression Omnibus (GEO) database, respectively. The coagulation factor-related prognostic model was constructed based on univariate, LASSO, and multivariate Cox regression analysis. In addition, colorectal cancer patients were classified into different subtypes according to non-negative matrix factorization (NMF) analysis. The nomogram and calibration curves were plotted to validate the accuracy of the coagulation factor-related prognostic model.Finally, the proportion of the infiltrating immune cells in different risk groups was analyzed by using immune cell infiltration Results: Seven coagulation factor-related genes were screened out to establish a prognostic model. The risk score of each colorectal cancer sample was calculated by the product of each prognostic coagulation factor-related gene with prognostic value and the corresponding gene expression of each prognostic coagulation factor-related gene. Patients with colorectal cancer were classified into high- and low-risk groups according to the median risk score. Survival curves indicated that colorectal cancer patients in the high-risk group had a worse prognosis both in the training set, internal validation set, and external validation set. Colorectal cancer patients were divided into three subtypes (subtype C1, subtype C2, and subtype C3) according to the optimal number of clusters. The nomogram we established was accurate to predict the overall survival of colorectal cancer patients. The Sankey plot suggested that colorectal cancer patients in the subtype C2 and low-risk group had a better prognosis. Finally, immune cell infiltration analysis indicated that macrophages might play an important role in the development of colorectal cancer. Conclusion: The coagulation factor-related prognostic model was established based on STIM1, PLCB1, MAPK12, F2RL2, C8G, C9, and ADCY5. The colorectal cancer patients were divided into three subtypes, including subtype C1, subtype C2, and subtype C3. These findings might provide novel therapeutic strategies for the treatment of patients with colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Coagulation Factor-Related Prognostic Model for Colorectal Cancer Based on the Public Database

Han

et al. 2023

Preprint

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“…There is an urgent need for new prognostic and diagnostic markers to enable personalized therapy because of the heterogeneity of HCC. SLC35G2 was focused on the methylation role in certain diseases [12,18,19]. DNA methylation is widely recognized as an epigenetic mechanism of gene regulation [20].…”

Section: Discussionmentioning

confidence: 99%

“…DNA methylation is widely recognized as an epigenetic mechanism of gene regulation [20]. SLC35G2, as one of the methylation-driver prognostic genes, had a prognostic risk score signature in hepatitis-positive HCC [12]. Aberrant methylation of the promoter CpG islands of SLC35G2 was found in melanocytes [18].…”

Section: Discussionmentioning

confidence: 99%

“…Previous research demonstrated the signi cance of SLC35G2 expression for cell proliferation in renal cell carcinoma [11]. SLC35G2 was utilized for the prognostic prediction of survival in patients with hepatitis-positive HCC [12]. SLC35G2 expression was upregulated in peripheral blood mononuclear cells (PBMs) one year after nephrectomy [13].…”

Section: Introductionmentioning

confidence: 99%

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SLC35G2 as a Prognostic Biomarker in Hepatocellular carcinoma and Its Correlation with Immunity

Yang

Lü

Huang

et al. 2023

Preprint

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Hepatocellular carcinoma (HCC) is the major cause of the worldwide cancer burden, especially in China. Solute Carrier Family 35 Member G2 (SLC35G2), a methylation-related gene, plays an essential role during tumorigenesis. However, its roles in key biological functions, the tumor microenvironment, mutations, and single-cell sequencing analysis remain unclear in HCC. This study aimed to identify the correlation between SLC35G2 and prognosis, biological roles, and immune features in HCC. The abnormal expression of SLC35G2 was associated with multiple tumor types, and there was a significant upregulation in HCC samples compared to normal tissues, which was an independent prognostic factor for predicting poor overall survival (OS) and disease-specific survival (DSS) in HCC. A nomogram based on SLC35G2, age, gender, histologic grade, and T-, N-, and M-stages was constructed, and the prognostic model performed well as shown by calibration curves for the 1-, 3-, and 5-year OS. Gene set enrichment analysis showed that SLC35G2 was closely related to tumorigenesis and immune response pathways, including Hippo-merlin, PI3K-AKT, IL-8, and IL-10 signaling pathways. In addition, SLC35G2 expression was inversely correlated with eosinophils and Th17 cells, and increased SLC35G2 expression was significantly associated with immune checkpoint molecules (GI24, CTLA4, PD-L1, B7-H3, TIM-3, and TGF-β). Furthermore, single-cell sequencing analysis showed that SLC35G2 expression was primarily localized in NK/T cells. In conclusion, SLC35G2 was identified as a new prognostic marker and had important potential implications for immunotherapy in HCC.

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“…DNA methylation is a major epigenetic modification and plays an important roles in carcinogenesis and progression (Fu et al 2022); and recent evidence has showed that driver methylation rather than passenger methylation are associated with cancer progression and prognosis (Pfeifer 2018; Kalari and Pfeifer 2010). Previous studies have suggested that LUAD could be stratified into different molecular subtypes by methylation signatures (Guidry et al 2022;Yu et al 2023;Smet 2023).…”

Section: Introductionmentioning

confidence: 99%

A novel subtype based on driver methylation–transcription in lung adenocarcinoma

Wang,

Xu,

Zhao

et al. 2024

J Cancer Res Clin Oncol

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Aims To identify driver methylation genes and a novel subtype of lung adenocarcinoma (LUAD) by multi-omics and elucidate its molecular features and clinical significance. Methods We collected LUAD patients from public databases, and identified driver methylation genes (DMGs) by MethSig and MethylMix algrothms. And novel driver methylation multi-omics subtypes were identified by similarity network fusion (SNF). Furthermore, the prognosis, tumor microenvironment (TME), molecular features and therapy efficiency among subtypes were comprehensively evaluated. Results 147 overlapped driver methylation were identified and validated. By integrating the mRNA expression and methylation of DMGs using SNF, four distinct patterns, termed as S1-S4, were characterized by differences in prognosis, biological features, and TME. The S2 subtype showed unfavorable prognosis. By comparing the characteristics of the DMGs subtypes with the traditional subtypes, S3 was concentrated in proximal-inflammatory (PI) subtype, and S4 was consisted of terminal respiratory unit (TRU) subtype and PI subtype. By analyzing TME and epithelial mesenchymal transition (EMT) features, increased immune infiltration and higher expression of immune checkpoint genes were found in S3 and S4. While S4 showed higher EMT score and expression of EMT associated genes, indicating S4 may not be as immunosensitive as the S3. Additionally, S3 had lower TIDE and higher IPS score, indicating its increased sensitivity to immunotherapy. Conclusion The driver methylation-related subtypes of LUAD demonstrate prognostic predictive ability that could help inform treatment response and provide complementary information to the existing subtypes.

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A novel DNA methylation‐driver gene signature for long‐term survival prediction of hepatitis‐positive hepatocellular carcinoma patients

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 4 publications

References 66 publications

Construction and Validation of a Coagulation Factor-Related Prognostic Model for Colorectal Cancer Based on the Public Database

Construction and Validation of a Coagulation Factor-Related Prognostic Model for Colorectal Cancer Based on the Public Database

SLC35G2 as a Prognostic Biomarker in Hepatocellular carcinoma and Its Correlation with Immunity

A novel subtype based on driver methylation–transcription in lung adenocarcinoma

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