Association of Genetic Ancestry and Molecular Signatures with Cancer Survival Disparities: A Pan-Cancer Analysis

Lee, Kara K.; Rishishwar, Lavanya; Ban, Dongjo; Nagar, Shashwat Deepali; Mariño-Ramírez, Leonardo; McDonald, John F.; Jordan, I. King

doi:10.1158/0008-5472.can-21-2105

Cited by 19 publications

(15 citation statements)

References 43 publications

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“…The expression level of CCNF in male patients is generally higher than that in female patients, which also suggests that CCNF is a potential pancancer therapeutic target influenced by sex. There are similar differences in patients grouped by race ( 45 , 46 ). In our study, the expression level of CCNF in Caucasians with BLCA and THYM cancer was significantly lower than that in African Americans but significantly higher than that in Asians.…”

Section: Discussionmentioning

confidence: 77%

CCNF is a potential pancancer biomarker and immunotherapy target

Wei

Xiao

et al. 2023

Front. Oncol.

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BackgroundCCNF catalyzes the transfer of ubiquitin molecules from E2 ubiquitin-conjugating enzymes to target proteins, thereby regulating the G1/S or G2/M transition of tumor cells. Thus far, CCNF expression and its potential as a pancancer biomarker and immunotherapy target have not been reported.MethodsTCGA datasets and the R language were used to analyze the pancancer gene expression, protein expression, and methylation levels of CCNF; the relationship of CCNF expression with overall survival (OS), recurrence-free survival (RFS), immune matrix scores, sex and race; and the mechanisms for posttranscriptional regulation of CCNF.ResultsCCNF expression analysis showed that CCNF mRNA expression was higher in cancer tissues than in normal tissues in the BRCA, CHOL, COAD, ESCA, HNSC, LUAD, LUSC, READ, STAD, and UCEC; CCNF protein expression was also high in many cancer tissues, indicating that it could be an important predictive factor for OS and RFS. CCNF overexpression may be caused by CCNF hypomethylation. CCNF expression was also found to be significantly different between patients grouped based on sex and race. Overexpression of CCNF reduces immune and stromal cell infiltration in many cancers. Posttranscriptional regulation analysis showed that miR-98-5p negatively regulates the expression of the CCNF gene.ConclusionCCNF is overexpressed across cancers and is an adverse prognostic factor in terms of OS and RFS in many cancers; this phenomenon may be related to hypomethylation of the CCNF gene, which could lead to cancer progression and worsen prognosis. In addition, CCNF expression patterns were significantly different among patients grouped by sex and race. Its overexpression reduces immune and stromal cell infiltration. miR-98-5p negatively regulates CCNF gene expression. Hence, CCNF is a potential pancancer biomarker and immunotherapy target.

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Section: Discussionmentioning

confidence: 77%

CCNF is a potential pancancer biomarker and immunotherapy target

Wei

Xiao

et al. 2023

Front. Oncol.

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“…In order to better explore the genomic profiles between the 3 clusters, we adopted the tumor molecular signatures across 33 cancers from the TCGA cohort ( 14 ), and identified that C1 had a remarkably higher aneuploidy score ( Figure 3A ), homologous recombination defects ( Figure 3B ), fraction altered ( Figure 3C ), and number of segments ( Figure 3D ), as compared with C3. The tumor mutation burden was higher in C3 than C2 ( Figure 3E ).…”

Section: Resultsmentioning

confidence: 99%

Identification and analysis of necroptosis-associated signatures for prognostic and immune microenvironment evaluation in hepatocellular carcinoma

Bao

et al. 2022

Front. Immunol.

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BackgroundHepatocellular carcinoma remains the third most common cause of cancer-related deaths worldwide. Although great achievements have been made in resection, chemical therapies and immunotherapies, the pathogenesis and mechanism of HCC initiation and progression still need further exploration. Necroptosis genes have been reported to play an important role in HCC malignant activities, thus it is of great importance to comprehensively explore necroptosis-associated genes in HCC.MethodsWe chose the LIHC cohort from the TCGA, ICGC and GEO databases for this study. ConsensusClusterPlus was adopted to identify the necroptosis genes-based clusters, and LASSO cox regression was applied to construct the prognostic model based on necroptosis signatures. The GSEA and CIBERSORT algorithms were applied to evaluate the immune cell infiltration level. QPCR was also applied in this study to evaluate the expression level of genes in HCC.ResultsWe identified three clusters, C1, C2 and C3. Compared with C2 and C3, the C1 cluster had the shortest overall survival time and highest immune score. The C1 was samples were significantly enriched in cell cycle pathways, some tumor epithelial-mesenchymal transition related signaling pathways, among others. The DEGs between the 3 clusters showed that C1 was enriched in cell cycle, DNA replication, cellular senescence, and p53 signaling pathways. The LASSO cox regression identified KPNA2, SLC1A5 and RAMP3 as prognostic model hub genes. The high risk-score subgroup had an elevated expression level of immune checkpoint genes and a higher TIDE score, which suggested that the high risk-score subgroup had a lower efficiency of immunotherapies. We also validated that the necroptosis signatures-based risk-score model had powerful prognosis prediction ability.ConclusionBased on necroptosis-related genes, we classified patients into 3 clusters, among which C1 had significantly shorter overall survival times. The proposed necroptosis signatures-based prognosis prediction model provides a novel approach in HCC survival prediction and clinical evaluation.

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“…MXD3, a member of the MXD family, plays pivotal roles in cell cycle progression and cell proliferation; it is regarded as an onco- Frontiers in Genetics frontiersin.org immunological biomarker (Wu et al, 2021). Moreover, pan-cancer analysis discovered that MXD3 interacted with gene ancestry (GA) and exacerbated observed survival disparities (Lee et al, 2022). Besides, MXD3 was reported to be a potential therapeutic target in pre-B cell acute lymphoblastic leukemia (Satake et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Identification of molecular subtypes and a prognostic signature based on chromatin regulators related genes in prostate cancer

Zhou

et al. 2023

Front. Genet.

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The clinical and molecular phenotypes of prostate cancer (PCa) exhibit substantial heterogeneity, ranging from indolent to metastatic disease. In this study, we aimed to identify PCa subtypes and construct a gene signature that can predict the recurrence-free survival (RFS) of PCa patients based on chromatin regulators genes (CRGs). Strikingly, we identified two heterogeneous subtypes with distinct clinical and molecular characteristics. Furthermore, by performing differential analysis between the two CRGs subtypes, we successfully constructed a gene signature to predict PCa prognosis. The signature, comprising four genes (MXD3, SSTR1, AMH and PPFIA2), was utilized to classify PCa patients into two risk groups; the high-risk group was characterized by poor prognosis and more aggressive clinical features. Moreover, we investigated the immune profile, mutation landscape and molecular pathways in each of the groups. Additionally, drug-susceptibility testing was performed to explore sensitive drugs for high-risk patients. Furthermore, we found that MXD3 downregulation suppressed the proliferation of PCa cell lines in vitro. Overall, our results highlight the signature based on CRGs as a powerful tool for predicting RFS of PCa patients, as well as an indicator for personalized treatment of those patients.

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Association of Genetic Ancestry and Molecular Signatures with Cancer Survival Disparities: A Pan-Cancer Analysis

Cited by 19 publications

References 43 publications

CCNF is a potential pancancer biomarker and immunotherapy target

CCNF is a potential pancancer biomarker and immunotherapy target

Identification and analysis of necroptosis-associated signatures for prognostic and immune microenvironment evaluation in hepatocellular carcinoma

Identification of molecular subtypes and a prognostic signature based on chromatin regulators related genes in prostate cancer

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