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    1. Genetic variants in the Folic acid Metabolic Pathway Genes predict outcomes of metastatic Colorectal Cancer patients receiving first-line Chemotherapy

      [Paper-level Aggregated] PMCID: PMC7545690

      Evidence Type(s): Prognostic, Predictive

      Justification: Prognostic: The variant rs3786362 in TYMS is associated with reduced progression-free survival (PFS) and overall survival (OS) in mCRC patients, indicating its potential as a prognostic marker for patient outcomes. Predictive: The study suggests that rs3786362 may serve as a predictive biomarker for survival in specific subgroups of mCRC patients, as it correlates with treatment response and survival outcomes based on genotype.

      Gene→Variant (gene-first): FTCD(10841):rs10432965 FOLH1(2346):rs369803 TYMS(7298):rs3786362 SLC46A1(113235):rs4795436

      Genes: FTCD(10841) FOLH1(2346) TYMS(7298) SLC46A1(113235)

      Variants: rs10432965 rs369803 rs3786362 rs4795436

    2. Results: We found that rs3786362 G allele of thymidylate synthase (TYMS) gene was significantly associated with PFS (P = 1.10 x 10-2), OS (P = 2.50 x 10-2) and DCR (P = 5.00 x 10-3). The expression of TYMS was overexpres

      [Paragraph-level] PMCID: PMC7545690 Section: ABSTRACT PassageIndex: 3

      Evidence Type(s): Prognostic, Diagnostic

      Justification: Prognostic: The passage indicates that the rs3786362 G allele is significantly associated with progression-free survival (PFS) and overall survival (OS), which are outcomes related to disease prognosis. Diagnostic: The association of the rs3786362 G allele with tumor characteristics suggests it may be used to classify or define disease subtypes, particularly in colorectal cancer (CRC).

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    3. Stratification analysis was also performed to evaluate the potential effects of TYMS rs3786362 in mCRC patients in the dominant model. Overall, the carriers of the risk G allele reduced PFS with respect to female, younge

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 15

      Evidence Type(s): Prognostic, Predictive

      Justification: Prognostic: The passage discusses how the rs3786362 variant correlates with progression-free survival (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC) patients, indicating its association with disease outcomes independent of therapy. Predictive: The passage suggests that TYMS rs3786362 could be a predictive biomarker for survival in mCRC patients, indicating a potential correlation with treatment response in specific subgroups.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    4. Stratification analysis of rs3786362 in TYMS and mCRC survival

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 14

      Evidence Type(s): Prognostic

      Justification: Prognostic: The passage indicates that rs3786362 is involved in stratification analysis related to mCRC survival, suggesting a correlation with disease outcome.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    5. In order to explore the correlation of rs3786362 in TYMS and responses to first-line chemotherapy in mCRC patients, we conducted three models including additive model, dominant model and recessive model for correlation a

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 13

      Evidence Type(s): Predictive

      Justification: Predictive: The passage discusses the correlation of the variant rs3786362 with responses to first-line chemotherapy in mCRC patients, indicating that the G allele is associated with reduced disease control rate (DCR), which relates to treatment response.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    6. The correlation between rs3786362 in TYMS and DCR of mCRC patients

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Predictive

      Justification: Predictive: The passage discusses the correlation between the variant rs3786362 and the disease control rate (DCR) in metastatic colorectal cancer (mCRC) patients, indicating a relationship with treatment response.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    7. Kaplan-Meier curves of PFS and OS for TYMS rs3786362 in mCRC patients were depicted choosing the dominant model. Patients with AG/GG genotypes exhibited reduced PFS and OS compared with AA genotype (Figure 2).

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 11

      Evidence Type(s): Prognostic, Diagnostic

      Justification: Prognostic: The passage discusses the correlation of the rs3786362 variant with progression-free survival (PFS) and overall survival (OS) in mCRC patients, indicating its association with disease outcome independent of therapy. Diagnostic: The variant rs3786362 is used to classify patients based on their genotypes (AG/GG vs. AA), which suggests its role in defining or associating with a disease subtype in mCRC.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    8. Owing to the positive findings of TYMS rs3786362 on PFS in our previous study, the correlation analysis of the selected SNP with OS was further conducted. Interestingly, TYMS rs3786362 was also associated with reduced OS

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Prognostic, Diagnostic

      Justification: Prognostic: The passage discusses the association of the variant rs3786362 with reduced overall survival (OS) and progression-free survival (PFS), indicating its correlation with disease outcomes independent of therapy. Diagnostic: The variant rs3786362 is associated with different genotypes (AG and AA) that correlate with reduced PFS and OS, suggesting its role in classifying disease outcomes based on genotype.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    9. The correlation between rs3786362 in TYMS and mCRC survival

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Prognostic

      Justification: Prognostic: The passage discusses the correlation between the variant rs3786362 and mCRC survival, indicating its association with disease outcome independent of therapy.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    10. We analyzed the association between 35 SNPs and PFS of mCRC patients in the additive model after genotyping (Supplementary Table S4). As shown in Table 1, we found that four SNPs (rs369803 in FOLH1, rs10432965 in FTCD, r

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Prognostic, Predictive

      Justification: Prognostic: The passage discusses the correlation of SNPs, specifically rs3786362 and rs369803, with progression-free survival (PFS) in metastatic colorectal cancer (mCRC) patients, indicating their association with disease outcome. Predictive: The passage mentions the correlation of SNPs with disease control rate (DCR), suggesting that these variants may influence treatment response in mCRC patients.

      Gene→Variant (gene-first): 10841:rs10432965 2346:rs369803 7298:rs3786362 113235:rs4795436

      Genes: 10841 2346 7298 113235

      Variants: rs10432965 rs369803 rs3786362 rs4795436

    11. Results: We found that rs3786362 G allele of thymidylate synthase (TYMS) gene was significantly associated with PFS (P = 1.10 x 10-2), OS (P = 2.50 x 10-2) and DCR (P = 5.00 x 10-3). The expression of TYMS was overexpres

      [Paragraph-level] PMCID: PMC7545690 Section: ABSTRACT PassageIndex: 3

      Evidence Type(s): Prognostic, Diagnostic

      Justification: Prognostic: The passage indicates that the rs3786362 G allele is significantly associated with progression-free survival (PFS) and overall survival (OS), which are outcomes related to disease prognosis. Diagnostic: The association of the rs3786362 G allele with tumor characteristics suggests it may be used to classify or define disease subtypes, particularly in colorectal cancer (CRC).

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    12. Stratification analysis was also performed to evaluate the potential effects of TYMS rs3786362 in mCRC patients in the dominant model. Overall, the carriers of the risk G allele reduced PFS with respect to female, younge

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 15

      Evidence Type(s): Prognostic, Predictive

      Justification: Prognostic: The passage discusses how the rs3786362 variant correlates with progression-free survival (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC) patients, indicating its association with disease outcomes independent of therapy. Predictive: The passage suggests that TYMS rs3786362 could be a predictive biomarker for survival in mCRC patients, indicating a potential correlation with treatment response in specific subgroups.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    13. Stratification analysis of rs3786362 in TYMS and mCRC survival

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 14

      Evidence Type(s): Prognostic

      Justification: Prognostic: The passage indicates that rs3786362 is involved in stratification analysis related to mCRC survival, suggesting a correlation with disease outcome.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    14. In order to explore the correlation of rs3786362 in TYMS and responses to first-line chemotherapy in mCRC patients, we conducted three models including additive model, dominant model and recessive model for correlation a

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 13

      Evidence Type(s): Predictive

      Justification: Predictive: The passage discusses the correlation of the variant rs3786362 with responses to first-line chemotherapy in mCRC patients, indicating that the G allele is associated with reduced disease control rate (DCR), which relates to treatment response.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    15. The correlation between rs3786362 in TYMS and DCR of mCRC patients

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Predictive

      Justification: Predictive: The passage discusses the correlation between the variant rs3786362 and the disease control rate (DCR) in metastatic colorectal cancer (mCRC) patients, indicating a relationship with treatment response.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    16. Kaplan-Meier curves of PFS and OS for TYMS rs3786362 in mCRC patients were depicted choosing the dominant model. Patients with AG/GG genotypes exhibited reduced PFS and OS compared with AA genotype (Figure 2).

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 11

      Evidence Type(s): Prognostic, Diagnostic

      Justification: Prognostic: The passage discusses the correlation of the rs3786362 variant with progression-free survival (PFS) and overall survival (OS) in mCRC patients, indicating its association with disease outcome independent of therapy. Diagnostic: The variant rs3786362 is used to classify patients based on their genotypes (AG/GG vs. AA), which suggests its role in defining or associating with a disease subtype in mCRC.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    17. Owing to the positive findings of TYMS rs3786362 on PFS in our previous study, the correlation analysis of the selected SNP with OS was further conducted. Interestingly, TYMS rs3786362 was also associated with reduced OS

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Prognostic, Diagnostic

      Justification: Prognostic: The passage discusses the association of the variant rs3786362 with reduced overall survival (OS) and progression-free survival (PFS), indicating its correlation with disease outcomes independent of therapy. Diagnostic: The variant rs3786362 is associated with different genotypes (AG and AA) that correlate with reduced PFS and OS, suggesting its role in classifying disease outcomes based on genotype.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    18. The correlation between rs3786362 in TYMS and mCRC survival

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Prognostic

      Justification: Prognostic: The passage discusses the correlation between the variant rs3786362 and mCRC survival, indicating its association with disease outcome independent of therapy.

      Gene→Variant (gene-first): 7298:rs3786362

      Genes: 7298

      Variants: rs3786362

    19. We analyzed the association between 35 SNPs and PFS of mCRC patients in the additive model after genotyping (Supplementary Table S4). As shown in Table 1, we found that four SNPs (rs369803 in FOLH1, rs10432965 in FTCD, r

      [Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Prognostic, Predictive

      Justification: Prognostic: The passage discusses the correlation of SNPs, specifically rs3786362 and rs369803, with progression-free survival (PFS) in metastatic colorectal cancer (mCRC) patients, indicating their association with disease outcome. Predictive: The passage mentions the correlation of SNPs with disease control rate (DCR), suggesting that these variants may influence treatment response in mCRC patients.

      Gene→Variant (gene-first): 10841:rs10432965 2346:rs369803 7298:rs3786362 113235:rs4795436

      Genes: 10841 2346 7298 113235

      Variants: rs10432965 rs369803 rs3786362 rs4795436