A novel tumor mutational burden-based risk model predicts prognosis and correlates with immune infiltration in ovarian cancer

Wang, Haoyu; Liu, Jingchun; Jiang, Yang; Wang, Zhi; Zhang, Zihui; Peng, Jiaxin; Wang, Ying; Li, Hong

doi:10.3389/fimmu.2022.943389

Cited by 24 publications

(23 citation statements)

References 106 publications

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“…According to our results, patients with EC (Table 2) and mucinous carcinoma (Supplementary Table 3) tended to have a higher ratio of TMB-high values. Zhu et al also documented that the TMB of mucinous tumors in their study was higher than that of HGSC and LGSC (56). However, limited by the sample sizes in our study, more patient data in a larger cohort will be collected to verify this conclusion.…”

Section: B Amentioning

confidence: 52%

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Clinical characterization and genomic landscape of gynecological cancers among patients attending a Chinese hospital

Jiang

Liu

et al. 2023

Front. Oncol.

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BackgroundGynecological cancers are the most lethal malignancies among females, most of which are associated with gene mutations. Few studies have compared the differences in the genomic landscape among various types of gynecological cancers. In this study, we evaluated the diversity of mutations in different gynecological cancers.MethodsA total of 184 patients with gynecological cancer, including ovarian, cervical, fallopian tube, and endometrial cancer, were included. Next-generation sequencing was performed to detect the mutations and tumor mutational burden (TMB). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were also conducted.ResultsWe found that 94.57% of patients had at least one mutation, among which single nucleotide variants, insertions and InDels were in the majority. TP53, PIK3CA, PTEN, KRAS, BRCA1, BRCA2, ARID1A, KMT2C, FGFR2, and FGFR3 were the top 10 most frequently mutated genes. Patients with ovarian cancer tended to have higher frequencies of BRCA1 and BRCA2 mutations, and the frequency of germline BRCA1 mutations (18/24, 75.00%) was higher than that of BRCA2 (11/19, 57.89%). A new mutation hotspot in BRCA2 (I770) was firstly discovered among Chinese patients with gynecological cancer. Patients with TP53, PIK3CA, PTEN, and FGFR3 mutations had significantly higher TMB values than those with wild-type genes. A significant cross was discovered between the enriched KEGG pathways of gynecological and breast cancers. GO enrichment revealed that the mutated genes were crucial for the cell cycle, neuronal apoptosis, and DNA repair.ConclusionVarious gynecological cancer types share similarities and differences both in clinical characterization and genomic mutations. Taken together with the results of TMB and enriched pathways, this study provided useful information on the molecular mechanism underlying gynecological cancers and the development of targeted drugs and precision medicine.

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Section: B Amentioning

confidence: 52%

“…Zhu et al. also documented that the TMB of mucinous tumors in their study was higher than that of HGSC and LGSC ( 56 ). However, limited by the sample sizes in our study, more patient data in a larger cohort will be collected to verify this conclusion.…”

Section: Discussionmentioning

confidence: 80%

Clinical characterization and genomic landscape of gynecological cancers among patients attending a Chinese hospital

Jiang

Liu

et al. 2023

Front. Oncol.

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“…TMB can determine the response of immunotherapy, thus affecting the prognosis of many cancer patients 16 . We conducted mutation analysis on HCC samples of two subgroups and the results revealed that TP53 and CTNNB represented a higher genetic mutation frequency than the low‐risk group (Figure 6A,B).…”

Section: Resultsmentioning

confidence: 99%

Characterization of neutrophil extracellular traps related gene pair for predicting prognosis in hepatocellular carcinoma

Qian

Ying

Xie

et al. 2023

The Journal of Gene Medicine

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BackgroundHepatocellular carcinoma (HCC) is a malignant disease with a high incidence rate, high mortality and poor prognosis. Neutrophil extracellular traps (NETs), as an extracellular reticular structure, promote the development and progression of cancer in the tumor microenvironment, and have a promising prospect as a prognostic indicator. In the present study, we elucidated the prognostic value of NET‐related genes.MethodsThe NETs gene pair of The Cancer Genome Atlas cohort was constructed by least absolute shrinkage and selection operator analysis. Samples from the International Cancer Genome Consortium were performed to verify its feasibility. Kaplan–Meier analysis was used to compare the overall survival (OS) rate of the two subgroups. The independent predictors of OS were determined by univariate and multivariate Cox analysis. Furthermore, Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were analyzed by gene set enrichment analysis. The single sample gene set enrichment analysis method was performed to deplore the relationship of risk score with tumor immune microenvironment. The GSE149614 dataset was applied as single cell RNA level validation. PCR was performed to the detect mRNA expression profiles of NETs‐related genes.ResultsOur analysis of the NETs‐related model provides a promising prospect as a prognostic indicator. The OS of high‐risk group patients was significantly reduced. The risk score was an important independent predictor of HCC prognosis. The Nomogram model suggested a favorable classification performance. The drug resistance and sensitivity of tumor cells to chemotherapeutics was significantly correlated with the prognostic gene expression. The immune status of the two risk groups showed a marked difference.ConclusionsThe novel prognostic gene pair and immune landscape could predict the prognosis of HCC patients and provide a new understanding of immunotherapy in HCC.

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“…OC is a primary gynecologic malignancies tumor, and most OC patients were diagnosed at an advanced stage that has a high ability to damage surrounding tissues, so the prognosis is poor among OC patients. [29] Accordingly, exploring effective biomarkers is crucial for OC patients. In this research, circMFN2 regulated CUL4B to promote OC progression via sponging miR-198, which is expected to provide a latent treatment strategy for patients with OC.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of circMFN2 inhibits cell progression and glycolysis by miR‐198/CUL4B pathway in ovarian cancer

Song

Chai

Liu

et al. 2023

J Biochem & Molecular Tox

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Circular RNA (circRNA) regulates malignant tumors, including ovarian cancer (OC). The present research study aimed to reveal the biological mechanism of circRNA mitofusin 2 (circMFN2) in OC. Cell biological behaviors were investigated using clonogenicity assay, EdU assay, transwell assay, and flow cytometry analysis. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and western blot analysis were implemented to detect the levels of circMFN2, miR‐198, Cullin 4B (CUL4B), and apoptosis‐related proteins. Glycolysis was assessed by glucose assay kit, lactate assay kit, and ATP level detection kit. The relationships among miR‐198, circMFN2, and CUL4B were verified by dual‐luciferase reporter assay and RNA immunoprecipitation assay. The xenograft mice model was used to analyze tumor growth in vivo. The expression of circMFN2 and CUL4B was increased, while miR‐330‐5p was decreased in OC tissues or cells. The absence of CircMFN2 hindered cell proliferation, migration, invasion, and glycolysis and promoted apoptosis in OC cells. We found that circMFN2 promoted CUL4B expression via sponging miR‐198. MiR‐198 depletion reversed circMFN2 knockdown‐induced effects in OC cells. Furthermore, CUL4B overexpression overturned the inhibitory effect of miR‐198 in OC cells. And the absence of circMFN2 inhibited tumor growth in vivo. CircMFN2 repressed OC progression by regulating the miR‐198/CUL4B axis.

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A novel tumor mutational burden-based risk model predicts prognosis and correlates with immune infiltration in ovarian cancer

Cited by 24 publications

References 106 publications

Clinical characterization and genomic landscape of gynecological cancers among patients attending a Chinese hospital

Clinical characterization and genomic landscape of gynecological cancers among patients attending a Chinese hospital

Characterization of neutrophil extracellular traps related gene pair for predicting prognosis in hepatocellular carcinoma

Knockdown of circMFN2 inhibits cell progression and glycolysis by miR‐198/CUL4B pathway in ovarian cancer

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