TYMS 2R3R polymorphism and DPYD [IVS]14+1G&gt;A mutation genes in Mexican colorectal cancer patients

Gallegos‐Arreola, Martha Patricia; Zúñiga‐González, Guillermo Moisés; Sánchez-López, Josefina Yoaly; Naranjo-Cruz, Alondra Yeraldi; Peralta-Leal, Valeria; Figuera, Luis E.; Puebla-Pérez, Ana Marı́a; Ronquillo-Carreón, Carlos; Puebla-Mora, Ana Graciela

doi:10.18388/abp.2017_2338

Cited by 13 publications

(8 citation statements)

References 29 publications

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“…[62][63][64] TYMS encodes for thymidylate synthase (TS), an enzyme involved in DNA replication and repair. 65 Some studies have proven that TYMS plays a role in cancer, and its expression indicates poor survival rate, but its role has not yet been studied in CC. 66,67 The 14 genes identified in this study are considered oncogenes in most tumors, and are indicators of poor prognosis of tumor patients.…”

Section: Discussionmentioning

confidence: 99%

Screening and Discovery of New Potential Biomarkers and Small Molecule Drugs for Cervical Cancer: A Bioinformatics Analysis

Qiu

Huang

Xiang

et al. 2020

Technol Cancer Res Treat

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Background: Cervical cancer (CC) is the second most common type of malignant tumor survival rate is low in advanced stage, metastatic, and recurrent CC patients. This study aimed at identifying potential genes and drugs for CC diagnosis and targeting therapies. Methods: Three GEO mRNA microarray datasets of CC tissues and non-cancerous tissues were analyzed for differentially expressed genes (DEGs) by limma package. GO (Gene Ontologies) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used to explore the relationships between the DEGs. Protein-protein interaction (PPI) of these genes was established by the STRING database. MCODE was used for screening significant modules in the PPI networks to select hub genes. Biochemical mechanisms of the hub genes were investigated with Metascape. GEPIA database was used for validating the core genes. According to these DEGs, molecular candidates for CC were recognized from the CMAP database. Results: We identified 309 overlapping DEGs in the 2 tissue-types. Pathway analysis revealed that the DEGs were involved in cell cycle, DNA replication, and p53 signaling. PPI networks between overlapping DEGs showed 68 high-connectivity DEGs that were chosen as hub genes. The GEPIA database showed that the expression levels of RRM2, CDC45, GINS2, HELLS, KNTC1, MCM2, MYBL2, PCNA, RAD54 L, RFC4, RFC5, TK1, TOP2A, and TYMS in CC tissues were significantly different from those in the healthy tissues and were significantly relevant to the OS of CC. We found 10 small molecules from the CMAP database that could change the trend of gene expression in CC tissues, including piperlongumine and chrysin. Conclusions: The 14 DEGs identified in this study could serve as novel prognosis biomarkers for the detection and forecasting of CC. Small molecule drugs like piperlongumine and chrysin could be potential therapeutic drugs for CC treatment.

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Section: Discussionmentioning

confidence: 99%

Screening and Discovery of New Potential Biomarkers and Small Molecule Drugs for Cervical Cancer: A Bioinformatics Analysis

Qiu

Huang

Xiang

et al. 2020

Technol Cancer Res Treat

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“…Obviously, if the germline variant could be considered a predictive parameter like the somatic ones, a less-invasive method would be available to individualise the FP-based treatment in naïve patients. Several recent studies have suggested that the TYMS TSER germline polymorphism may be useful to prevent toxicity [57], such as hand-foot syndrome and other ADR types, including haematological and gastrointestinal ones [58]. With regards to the clinical cases described in Table 1, case 1 was homozygous TYMS TSER-2R/2R and case 2 and 3 were heterozygous 2R/3R.…”

Section: Discussionmentioning

confidence: 97%

A Genotyping/Phenotyping Approach with Careful Clinical Monitoring to Manage the Fluoropyrimidines-Based Therapy: Clinical Cases and Systematic Review of the Literature

Conti

Bellis

Manzo

et al. 2020

JPM

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Fluoropyrimidines (FP) are mainly metabolised by dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. FP pharmacogenetics, including four DPYD polymorphisms (DPYD-PGx), is recommended to tailor the FP-based chemotherapy. These polymorphisms increase the risk of severe toxicity; thus, the DPYD-PGx should be performed prior to starting FP. Other factors influence FP safety, therefore phenotyping methods, such as the measurement of 5-fluorouracil (5-FU) clearance and DPD activity, could complement the DPYD-PGx. We describe a case series of patients in whom we performed DPYD-PGx (by real-time PCR), 5-FU clearance and a dihydrouracil/uracil ratio (as the phenotyping analysis) and a continuous clinical monitoring. Patients who had already experienced severe toxicity were then identified as carriers of DPYD variants. The plasmatic dihydrouracil/uracil ratio (by high-performance liquid chromatography (HPLC)) ranged between 1.77 and 7.38. 5-FU clearance (by ultra-HPLC with tandem mass spectrometry) was measured in 3/11 patients. In one of them, it reduced after the 5-FU dosage was halved; in the other case, it remained high despite a drastic dosage reduction. Moreover, we performed a systematic review on genotyping/phenotyping combinations used as predictive factors of FP safety. Measuring the plasmatic 5-FU clearance and/or dihydrouracil/uracil (UH2/U) ratio could improve the predictive potential of DPYD-PGx. The upfront DPYD-PGx combined with clinical monitoring and feasible phenotyping method is essential to optimising FP-based chemotherapy.

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“…In this study, based on the expression profile data of cervical cancer in GEO and TCGA, through PPI, functional enrichment, Kaplan-Meier plotter analysis, Cox univariate and multivariate analysis, WGCNA and other bioinformatics analysis methods, we screened the factor, TYMS, which was significantly correlated with the prognosis of cervical cancer. TYMS is located on chromosome 18p and encodes thymine synthetase (TS), which is an essential enzyme involved in DNA replication and repair, and plays an important role in the biosynthesis of dTMP ( Gallegos-Arreola et al,2018 ; Fu et al,2019 ). Its role in tumor cell proliferation has been reported.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Hub Genes and miRNA-mRNA Pairs Related to the Progression and Prognosis of Cervical Cancer Through Integrated Bioinformatics Analysis

Pei

Lü

et al. 2021

Front. Genet.

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In recent years, the incidence and mortality of cervical cancer have increased worldwide. At the same time, increasing data have confirmed that miRNA-mRNA plays a positive or negative regulatory role in many cancers. This study attempted to screen effective miRNA-mRNA in the progression of cervical cancer, and to study the mechanism of miRNA-mRNA in the progression of cervical cancer. The expression profile data of GSE7410, GSE 63514, GSE 86100 and TCGA-CESC were downloaded, and 34 overlapping differentially expressed genes (22 up-regulated and 12 down-regulated) and 166 miRNAs (74 down-regulated and 92 up-regulated) were screened through limma package. Then, miR-197-3p/TYMS pairs were obtained by PPI, functional enrichment, Kaplan-Meier plotter analysis, Cox univariate and multivariate analysis, risk modeling, WGCNA, qPCR and dual-luciferase experiments. The results showed that TYMS was an independent prognostic factor of cervical cancer, and its expression level was negatively correlated with cervical cancer tissue grade (TMN), tumor grade, age, microsatellite stability and tumor mutation load, and positively correlated with methyl expression in DNMT1, DNMT2, DNMT3A and DNMT3B. Functional experiments showed that TYMS knockout could promote the proliferation, migration and invasion of HeLa cells and reduce apoptosis. Overexpression of TYMS showed the opposite trend, miR-197-3p was negatively correlated with the expression of TYMS. MiR-197-3p inhibitor reversed the effect of si-TYMS on the proliferation of HeLa cells. In conclusion, these results reveal that TYMS plays a very important role in the prognosis and progression of cervical cancer, and has the potential to be thought of as cervical cancer biomarkers. At the same time, miR-197-3p/TYMS axis can regulate the deterioration of cervical cancer cells, which lays a foundation for the molecular diagnosis and treatment of cervical cancer.

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TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A mutation genes in Mexican colorectal cancer patients

Abstract: TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD was not associated with susceptibility to CRC. However, the 2R/2R and 2R/3R genotypes of TYMS polymorphism could significantly contribute to hematological and gastric toxicity in CRC patients in this sample population.

Cited by 13 publications

References 29 publications

Screening and Discovery of New Potential Biomarkers and Small Molecule Drugs for Cervical Cancer: A Bioinformatics Analysis

Screening and Discovery of New Potential Biomarkers and Small Molecule Drugs for Cervical Cancer: A Bioinformatics Analysis

A Genotyping/Phenotyping Approach with Careful Clinical Monitoring to Manage the Fluoropyrimidines-Based Therapy: Clinical Cases and Systematic Review of the Literature

Identification of Potential Hub Genes and miRNA-mRNA Pairs Related to the Progression and Prognosis of Cervical Cancer Through Integrated Bioinformatics Analysis

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