A Nomogram Based on a Three-Gene Signature Derived from AATF Coexpressed Genes Predicts Overall Survival of Hepatocellular Carcinoma Patients

Li, Jun; Lu, Jianjun; Ma, Zhu; Li, Wenli

doi:10.1155/2020/7310768

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…COX regression and Kaplan-Meier analyses suggested an association between high SLC41A3 expression and poor OS and DSS in LIHC and KIRC. This result is consistent with our previous study that showed SLC41A3 is a prognostic factor in LIHC patients ( 43 ). Aberrant SLC41A3 expression may exert impact on cancer progression, in part, through influence on mechanisms that maintaining genome stability.…”

Section: Discussionsupporting

confidence: 94%

A Comprehensive Prognostic and Immune Analysis of SLC41A3 in Pan-Cancer

Zhang

Dai

et al. 2021

Front. Oncol.

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SLC41A3, as a member of the 41st family of solute carriers, participates in the transport of magnesium. The role of SLC41A3 in cancer prognosis and immune regulation has rarely been reported. This study was designed to analyze the expression status and prognostic significance of SLC41A3 in pan-cancers. The mRNA expression profiles of SLC41A3 were obtained from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), the Broad Institute Cancer Cell Line Encyclopedia (CCLE), and the International Cancer Genome Consortium (ICGC). The Cox regression and Kaplan-Meier analyses were used to evaluate the prognostic value of SLC41A3 in pan-cancer. Furthermore, the correlation between SLC41A3 expression and immune cells infiltration, immune checkpoint, mismatch repair (MMR), DNA methyltransferase (DNMT), tumor mutation burden (TMB), and microsatellite instability (MSI) were calculated using data form TCGA database. The results showed that the expression of SLC41A3 was down-regulated in kidney renal clear cell carcinoma (KIRC), and was associated with poor overall survival and tumor-specific mortality. Whereas, the expression of SLC41A3 was up-regulated in liver hepatocellular carcinoma (LIHC), and the results of Cox regression analysis revealed that SLC41A3 was an independent factor for LIHC prognosis. Meanwhile, a nomogram including SLC41A3 and stage was built and exhibited good predictive power for the overall survival of LIHC patients. Additionally, correlation analysis suggested a significant correlation between SLC41A3 and TMB, MSI, MMR, DNMT, and immune cells infiltration in various cancers. The overall survival and disease-specific survival analysis revealed that the combined SLC41A3 expression and immune cell score, TMB, and MSI were significantly associated with clinical outcomes in ACC, LIHC, and UVM patients. Therefore, we proposed that SLC41A3 may serve as a potential prognostic biomarker for cancer.

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Section: Discussionsupporting

confidence: 94%

A Comprehensive Prognostic and Immune Analysis of SLC41A3 in Pan-Cancer

Zhang

Dai

et al. 2021

Front. Oncol.

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“… 11 AATF expression is elevated in hepatocellular carcinoma and contributes to poor prognosis. 15 Our results showed that AATF was overexpressed in 48.6% bladder cancer tissues which positively associated with T stage. This was also supported by data from Oncomine showing AATF upregulation in BC tissues.…”

Section: Discussionmentioning

confidence: 51%

AATF is Overexpressed in Human Bladder Cancer and Regulates Chemo-Sensitivity Through Survivin

Tan¹,

Fu²,

Dong³

2021

OTT

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Objective Dysregulation of apoptosis antagonizing transcription factor (AATF) has been reported to be closely associated with human cancers. However, its involvement in human bladder cancer (BC) remains unexplored. This study aimed to investigate the clinical significance and biological roles of AATF in human bladder cancers. Methods AATF protein expression was examined in 107 cases of bladder cancer tissues using immunohistochemistry. AATF plasmid transfection and small interfering RNA (siRNA) knockdown were performed in T24 and 5637 cell lines. CCK-8, colony formation, annexin V/PI, JC-1 staining, and Western blotting were carried out to investigate the biological roles and underlying mechanisms of AATF in bladder cancer cells. Results Our results showed that AATF expression was upregulated in human bladder cancer specimens and correlated with T stage. Analysis of the Oncomine database showed elevation of AATF mRNA in BC tissues. The Cancer Genome Atlas (TCGA) data suggested that high AATF expression correlated with poor patient survival. Western blotting showed that AATF protein expression was higher in BC cell lines compared to normal bladder transitional epithelial cell line SV-HUC-1. CCK-8 and colony assays showed that ectopic AATF expression upregulated cell growth rate and colony numbers. CCK-8, annexin V/propidium iodide (PI), JC-1 assays and Western blotting showed that AATF overexpression decreased cisplatin sensitivity, downregulated cisplatin-induced apoptosis and upregulated mitochondrial membrane potential, with decreased cytochrome c and cleaved-PARP expression. AATF siRNA knockdown showed the opposite effects. Mechanistically, AATF overexpression upregulated cyclin E and Survivin at both mRNA and protein levels. The decreased cisplatin sensitivity/apoptosis induced by ectopic AATF were reversed after treatment with Survivin inhibitor YM155. Conclusion Our results showed that AATF was overexpressed in human bladder cancers and promoted malignant behavior by regulating cyclin E and Survivin, indicating AATF could serve as a malignant biomarker and potential therapeutic target in BC.

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“…The prognostic module proposed in our analysis was composed of CDCA8, KIF20A, KIF2C and CEP55, all of which are often reported as being dysregulated in HCC tissues (27)(28)(29)(30). First, cell division cycle associated 8 (CDCA8) is regarded as a significant oncogene that is involved in the pathological development of various cancers, including HCC (27) and pancreatic ductal adenocarcinoma (31).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Four-Gene Signature Correlated With the Prognosis of Patients With Hepatocellular Carcinoma: A Comprehensive Analysis

Zhu

2021

Front. Oncol.

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PurposeHepatocellular carcinoma (HCC) is a common solid-tumor malignancy with high heterogeneity, and accurate prognostic prediction in HCC remains difficult. This analysis was performed to find a novel prognostic multigene signature.MethodsThe TCGA-LIHC dataset was analyzed for differentially coexpressed genes through weighted gene coexpression network analysis (WGCNA) and differential gene expression analysis. A protein-protein interaction (PPI) network and univariate Cox regression analysis of overall survival (OS) were utilized to identify their prognostic value. Next, we used least absolute shrinkage and selection operator (LASSO) Cox regression to establish a prognostic module. Subsequently, the ICGC-LIRI-JP dataset was applied for further validation. Based on this module, HCC cases were stratified into high-risk and low-risk groups, and differentially expressed genes (DEGs) were identified. Functional enrichment analyses of these DEGs were conducted. Finally, single-sample gene set enrichment analysis (ssGSEA) was performed to explore the correlation between the prognostic signature and immune status.ResultsA total of 393 differentially coexpressed genes were obtained. Forty differentially coexpressed hub genes were identified using the CytoHubba plugin, and 38 of them were closely correlated with OS. Afterward, we established the four-gene prognostic signature with an acceptable accuracy (area under the curve [AUC] of 1-year survival: 0.739). The ICGC-LIRI-JP dataset also supported the acceptable accuracy (AUC of 1-year survival:0.752). Compared with low-risk cohort, HCC cases in the high-risk cohort had shorter OS, higher tumor grades, and higher T stages. The risk scores of this signature still act as independent predictors of OS (P<0.001). Functional enrichment analyses suggest that it was mainly organelle fission and nuclear division that were enriched. Finally, ssGSEA revealed that this signature is strongly associated with the immune status of HCC patients.ConclusionsThe proposed prognostic signature of four differentially coexpressed hub genes has satisfactory prognostic ability, providing important insight into the prediction of HCC prognosis.

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A Nomogram Based on a Three-Gene Signature Derived from AATF Coexpressed Genes Predicts Overall Survival of Hepatocellular Carcinoma Patients

Cited by 9 publications

References 24 publications

A Comprehensive Prognostic and Immune Analysis of SLC41A3 in Pan-Cancer

A Comprehensive Prognostic and Immune Analysis of SLC41A3 in Pan-Cancer

AATF is Overexpressed in Human Bladder Cancer and Regulates Chemo-Sensitivity Through Survivin

Identification of a Novel Four-Gene Signature Correlated With the Prognosis of Patients With Hepatocellular Carcinoma: A Comprehensive Analysis

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