The association of a genetic variant in CDKN2A/B gene and the risk of colorectal cancer

Rahmani, Farzad; Avan, Amir; Amerizadeh, Forouzan; Ferns, Gordon A.; Talebian, Sahar; Shahidsales, Soodabeh

doi:10.17179/excli2020-2051

Cited by 4 publications

(4 citation statements)

References 33 publications

(39 reference statements)

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“…CDKN2A promotes CRC metastasis by inducing epithelialmesenchymal transition [30] . A previous study demonstrated that CDKN2A was associated with poorer outcomes in patients with CRC [31] . Consequently, CDKN2A expression can be used as a prognostic marker for CRC [32] .…”

Section: Discussionmentioning

confidence: 94%

Comprehensive Analysis of Cuproptosis-related Genes in Prognosis and Tumor Microenvironment Infiltration in Colorectal Cancer

Chen

Liu

et al. 2023

Preprint

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Colorectal cancer (CRC) is a common malignancy, with high incidence and mortality rates. Cuproptosis, a novel form of copper-induced programmed cell death, contributes to tumor progression. Whether cuproptosis-related genes (CRGs) play a role in CRC remains unclear. Here, we systematically assessed CRG mutations in CRC. Seven of the 10 CRGs exhibited significant differential expression between CRC and normal tissues. CDKN2Aand DLAT were identified as independent risk factors for predicting overall survival (OS) in CRC using univariate and multivariate Cox analyses, and a risk score model was constructed based on CDKN2A and DLAT. Patients with CRC were categorized into high- and low-risk groups based on their median risk scores. Patients with CRC in the low-risk group had longer OS than those in the high-risk group. Receiver operating characteristic curve analysis indicated that the risk score model had good predictive accuracy for OS. Spearman’s analysis showed that CDKN2A and DLAT expressions were significantly associated with immune cell infiltration in CRC. Our research revealed CRGs’ prognostic value, particularly CDKN2A and DLAT, in CRC and demonstrated the relationship between CDKN2A/DLAT and immune infiltration in CRC, thereby contributing to the outcome evaluation of patients with CRC and identifying novel targets for CRC immunotherapy.

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Section: Discussionmentioning

confidence: 94%

Comprehensive Analysis of Cuproptosis-related Genes in Prognosis and Tumor Microenvironment Infiltration in Colorectal Cancer

Chen

Liu

et al. 2023

Preprint

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“…CDKN2A promotes CRC metastasis by inducing epithelialmesenchymal transition [31] . A previous study demonstrated that CDKN2A was associated with poorer outcomes in patients with CRC [32] . Consequently, CDKN2A expression can be used as a prognostic marker for CRC [33] .…”

Section: Discussionmentioning

confidence: 94%

Comprehensive Analysis of Cuproptosis-related Genes in Prognosis and Tumor Microenvironment Infiltration in Colorectal Cancer

Chen

Liu

et al. 2023

Preprint

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a common malignancy, with high incidence and mortality rates. Cuproptosis, a novel form of copper-induced programmed cell death, contributes to tumor progression. Whether cuproptosis-related genes (CRGs) play a role in CRC remains unclear. Here, we systematically assessed CRG mutations in CRC. Seven of the 10 CRGs exhibited significant differential expression between CRC and normal tissues. CDKN2A and DLAT were identified as independent risk factors for predicting overall survival (OS) in CRC using univariate and multivariate Cox analyses, and a risk score model was constructed based on CDKN2A and DLAT. Patients with CRC were categorized into high- and low-risk groups based on their median risk scores. Patients with CRC in the low-risk group had longer OS than those in the high-risk group. Receiver operating characteristic curve analysis indicated that the risk score model had good predictive accuracy for OS. Spearman’s analysis showed that CDKN2A and DLAT expressions were significantly associated with immune cell infiltration and immune checkpoints in CRC. Our research revealed CRGs’ prognostic value, particularly CDKN2A and DLAT, in CRC and demonstrated the relationship between CDKN2A/DLAT and immune infiltration in CRC, thereby contributing to the outcome evaluation of patients with CRC and identifying novel targets for CRC immunotherapy.

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“…The above findings align with the fact that CDKN2A is a key player in cell cycle regulation and its importance as a tumor suppressor gene [ 22 ]. Therefore, upregulation of this gene would cause drastic effects on the cell cycle as well as other cellular functions and components which may lead to cancer progression [ 25 ] and this leads to the genetic comprehension of the gene in terms of mutation or epigenetic perspective and how it positively impacts the gene expression [ 25 ] and its recurrence with regard to the age, race, gender, or even body weight.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Pan-Cancer Analysis Reveals Cyclin-Dependent Kinase Inhibitor 2A Gene as a Potential Diagnostic and Prognostic Biomarker in Colon Adenocarcinoma

Salem,

Ahmed,

Khalfallah

et al. 2024

Cureus

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Introduction Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a suppressor carcinogenic gene that is upregulated across various types of cancer including breast, liver, thyroid, and bile duct cancer due to its crucial role in cell cycle regulation and cell division. Nevertheless, it is mostly investigated at the genetic level, but it is still poorly studied on pan-cancer analysis as a biomarker and this study shows its significant potential diagnostic and prognostic characteristics. However, this study aims to investigate the role of CDKN2A as a diagnostic and prognostic biomarker across various types of cancer focusing primarily on colon adenocarcinoma (COAD). Methods We investigated CDKN2A gene expression in a pan-cancer analysis across different types of cancer to show its diagnostic potential characteristics by using various bioinformatic tools, including Tumor Immune Estimation Resource (TIMER) 2.0, Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) database. TIMER was used to profile gene expression across 32 types of cancer composed of 10,000 RNA-seq samples obtained from the Cancer Genome Atlas (TCGA) and to analyze the tumor-infiltrating immune cells. In addition, GEPIA and UALCAN were further used to analyze gene expression, in terms of gene regulation, pathological stages, and clinical parameters, including gender, age, and race. Therefore, we used GEPIA, UALCAN, and Kaplan-Meier plotter particularly across adenocarcinoma to investigate CDKN2A prognosis by studying its high expression association with the patient’s overall survival rate to show the tumor progression. Then, we looked into the genetic alteration of CDKN2A by using the cBio Cancer Genomics Portal (cBioPortal), including 10 pan-cancer studies. We concluded the analysis with gene validation by using a public cohort in Gene Expression Omnibus (GEO). Results CDKN2A showed a trend of upregulation in most cancers and it was significantly upregulated in five cancers, which were commonly identifiable in three databases, including breast invasive carcinoma (p < 0.001), kidney chromophobe (p < 0.001), kidney renal clear cell carcinoma (p < 0.001), kidney renal papillary cell carcinoma (p < 0.001), and COAD (p < 0.001). The upregulation was significantly different in association with pathogenic stages II and III (pr(>F) = 0.00234) which was identifiable significantly in COAD more than in other cancers. The gene showed a high upregulation in association with poor prognosis of patient survival in three cancers, including COAD (log-rank p = 0.011), mesothelioma (log-rank p = 5.9e−07), and liver hepatocellular carcinoma (log-rank p = 0.0045). Therefore, COAD was the only comprehensively analyzed tumor to show a diagnostic and prognostic potential characteristic during high upregulation of CDKN2A. Furthermore, CDKN2A displayed a rare mutation in the form of deep deletion (9%) and revealed an upregulation associate...

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The association of a genetic variant in CDKN2A/B gene and the risk of colorectal cancer

Cited by 4 publications

References 33 publications

Comprehensive Analysis of Cuproptosis-related Genes in Prognosis and Tumor Microenvironment Infiltration in Colorectal Cancer

Comprehensive Analysis of Cuproptosis-related Genes in Prognosis and Tumor Microenvironment Infiltration in Colorectal Cancer

Comprehensive Analysis of Cuproptosis-related Genes in Prognosis and Tumor Microenvironment Infiltration in Colorectal Cancer

A Comprehensive Pan-Cancer Analysis Reveals Cyclin-Dependent Kinase Inhibitor 2A Gene as a Potential Diagnostic and Prognostic Biomarker in Colon Adenocarcinoma

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