Pancancer analysis of the prognostic and immunological role of FANCD2: a potential target for carcinogenesis and survival

Zhao, Zedan; Wang, Ruyu; Wang, Ruixue; Song, Jialing; Ma, Fengjun; Pan, Huafeng; Gao, Cuiyun; Wang, Deqiang; Chen, Xuemei; Fan, Xiangzhen

doi:10.1186/s12920-024-01836-4

Cited by 3 publications

(5 citation statements)

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“…Several studies point out to an important role of FANCD2 in the initiation, development and progression of diverse tumors. To this regard, a recently published pan-cancer bioinformatics analysis, integrating several parameters such as gene expression and regulation, prognosis, and mutations across multiple cancer types, has shown that high FANCD2 expression was associated with poor prognosis in certain tumors ( Zhao et al, 2024 ). On the whole, overall survival, disease-specific survival, or progression-free intervals was related to FANCD2 expression in certain cancerous tissues, including those of lung, breast, liver, and colon ( Zhao et al, 2024 ).…”

Section: Discussionmentioning

confidence: 99%

“…To this regard, a recently published pan-cancer bioinformatics analysis, integrating several parameters such as gene expression and regulation, prognosis, and mutations across multiple cancer types, has shown that high FANCD2 expression was associated with poor prognosis in certain tumors (Zhao et al, 2024). On the whole, overall survival, disease-specific survival, or progression-free intervals was related to FANCD2 expression in certain cancerous tissues, including those of lung, breast, liver, and colon (Zhao et al, 2024). Receiver Operating Curve (ROC) analysis on CHOL-TCGA dataset related to the four RBP transcripts, with their AUC values associated with the 95% Confidence Interval.…”

Section: Discussionmentioning

confidence: 99%

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RNA-binding protein transcripts as potential biomarkers for detecting Primary Sclerosing Cholangitis and for predicting its progression to Cholangiocarcinoma

Ala,

Fagoonee

2024

Front. Mol. Biosci.

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Primary Sclerosing Cholangitis (PSC) is a persistent inflammatory liver condition that affects the bile ducts and is commonly diagnosed in young individuals. Despite efforts to incorporate various clinical, biochemical and molecular parameters for diagnosing PSC, it remains challenging, and no biomarkers characteristic of the disease have been identified hitherto. PSC is linked with an uncertain prognosis, and there is a pressing need to explore multiomics databases to establish a new biomarker panel for the early detection of PSC’s gradual progression into Cholangiocarcinoma (CCA) and for the development of effective therapeutic interventions. Apart from non-coding RNAs, other components of the Ribonucleoprotein (RNP) complex, such as RNA-Binding Proteins (RBPs), also hold great promise as biomarkers due to their versatile expression in pathological conditions. In the present review, an update on the RBP transcripts that show dysregulated expression in PSC and CCA is provided. Moreover, by utilizing a bioinformatic data mining approach, we give insight into those RBP transcripts that also exhibit differential expression in liver and gall bladder, as well as in body fluids, and are promising as biomarkers for diagnosing and predicting the prognosis of PSC. Expression data were bioinformatically extracted from public repositories usingTCGA Bile Duct Cancer dataset for CCA and specific NCBI GEO datasets for both PSC and CCA; more specifically, RBPs annotations were obtained from RBP World database. Interestingly, our comprehensive analysis shows an elevated expression of the non-canonical RBPs, FANCD2, as well as the microtubule dynamics regulator, ASPM, transcripts in the body fluids of patients with PSC and CCA compared with their respective controls, with the same trend in expression being observed in gall bladder and liver cancer tissues. Consequently, the manipulation of tissue expression of RBP transcripts might be considered as a strategy to mitigate the onset of CCA in PSC patients, and warrants further experimental investigation. The analysis performed herein may be helpful in the identification of non-invasive biomarkers for the early detection of PSC and for predicting its progression into CCA. In conclusion, future clinical research should investigate in more depth the full potential of RBP transcripts as biomarkers for human pathologies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

RNA-binding protein transcripts as potential biomarkers for detecting Primary Sclerosing Cholangitis and for predicting its progression to Cholangiocarcinoma

Ala,

Fagoonee

2024

Front. Mol. Biosci.

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“…In contrast, a study conducted on 181 ovarian cancer patients provided evidence of an increased survival rate in patients with the FANCD2 mutation [ 61 ]. On the basis of its upregulation, FANCD2 may contribute to tumorigenesis and impart an unfavorable prognosis to various types of cancers, including esophageal squamous cell carcinoma, head and neck cancer, nasopharyngeal carcinoma, and lung adenocarcinoma [ 62 , 63 , 64 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Validation of the Somatic FANCD2 Mutation (c.2022-5C>T) as a Novel Molecular Biomarker for Early Disease Progression in Chronic Myeloid Leukemia: A Case–Control Study

Alanazi,

Siyal,

Basit

et al. 2024

Hematology Reports

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Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients’ blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials.

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“…So far, multiple studies have included TGCT data but have obtained underwhelming results. For instance, FANCD2upregulated expression may be involved in tumor initiation, development, and progress and shows significant prognostic value in various types of cancers, including hepatocellular carcinoma, lung adenocarcinoma, and non-muscle invasive bladder cancer [47]. A decrease in methylation correlated with its overexpression was observed in a pan-cancer TCGAbased study which included TGCT, but no significant results were obtained for this type [47].…”

Section: Dna Methylation As a Biomarkermentioning

confidence: 96%

“…For instance, FANCD2upregulated expression may be involved in tumor initiation, development, and progress and shows significant prognostic value in various types of cancers, including hepatocellular carcinoma, lung adenocarcinoma, and non-muscle invasive bladder cancer [47]. A decrease in methylation correlated with its overexpression was observed in a pan-cancer TCGAbased study which included TGCT, but no significant results were obtained for this type [47]. Another example concerns Cytoplasmic FMR Interacting Protein 2 (CYFIP2), which is a p53-inducible gene possibly involved in tumor initiation and progression.…”

Section: Dna Methylation As a Biomarkermentioning

confidence: 99%

Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship

Nicu,

Ionel,

Stoica

et al. 2024

Biomedicines

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Testicular germ cell tumors (TGCTs) are the most common type of testicular cancer, with a particularly high incidence in the 15–45-year age category. Although highly treatable, resistance to therapy sometimes occurs, with devastating consequences for the patients. Additionally, the young age at diagnosis and the treatment itself pose a great threat to patients’ fertility. Despite extensive research concerning genetic and environmental risk factors, little is known about TGCT etiology. However, epigenetics has recently come into the spotlight as a major factor in TGCT initiation, progression, and even resistance to treatment. As such, recent studies have been focusing on epigenetic mechanisms, which have revealed their potential in the development of novel, non-invasive biomarkers. As the most studied epigenetic mechanism, DNA methylation was the first revelation in this particular field, and it continues to be a main target of investigations as research into its association with TGCT has contributed to a better understanding of this type of cancer and constantly reveals novel aspects that can be exploited through clinical applications. In addition to biomarker development, DNA methylation holds potential for developing novel treatments based on DNA methyltransferase inhibitors (DNMTis) and may even be of interest for fertility management in cancer survivors. This manuscript is structured as a literature review, which comprehensively explores the pivotal role of DNA methylation in the pathogenesis, progression, and treatment resistance of TGCTs.

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Pancancer analysis of the prognostic and immunological role of FANCD2: a potential target for carcinogenesis and survival

Cited by 3 publications

References 55 publications

RNA-binding protein transcripts as potential biomarkers for detecting Primary Sclerosing Cholangitis and for predicting its progression to Cholangiocarcinoma

RNA-binding protein transcripts as potential biomarkers for detecting Primary Sclerosing Cholangitis and for predicting its progression to Cholangiocarcinoma

Clinical Validation of the Somatic FANCD2 Mutation (c.2022-5C>T) as a Novel Molecular Biomarker for Early Disease Progression in Chronic Myeloid Leukemia: A Case–Control Study

Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship

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