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  2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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    1. karim2001khoury 19 Feb 2026
      Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer

      [Paper-level Aggregated] PMCID: PMC7472556

      Evidence Type(s): Oncogenic, Diagnostic, Prognostic

      Justification: Oncogenic: The text discusses the upregulation of NRG1 in response to hormone therapy and its association with promoting resistance to androgen deprivation therapy (ADT), indicating a role in cancer progression. Diagnostic: The detection of NRG1 expression using an immunohistochemical assay in patients with localized prostate cancer suggests its potential use as a diagnostic marker for assessing treatment response. Prognostic: The correlation between NRG1 expression and patient outcomes, particularly in relation to ADT treatment, implies that NRG1 levels may serve as a prognostic indicator for treatment efficacy in prostate cancer.

      Gene→Variant (gene-first): RET(5979):Q8 NRG1(3084):S6 KAT2B(8850):S7 KAT2B(8850):S7C

      Genes: RET(5979) NRG1(3084) KAT2B(8850)

      Variants: Q8 S6 S7 S7C

      CIViC paper-level aggregated PMC7472556
    2. karim2001khoury 19 Feb 2026
      To examine if upregulation of NRG1 is induced by hormone therapy, we treated freshly isolated primary CAFs from CWR22Pc tumors or pCAFs with CSS or Enz. CSS and Enz both induced NRG1 mRNA and protein expression after 7 d

      [Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 23

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses how NRG1 levels increase after androgen deprivation therapy (ADT) and suggests that these elevated levels are sufficient to promote resistance to ADT, indicating a correlation with treatment response. Oncogenic: The mention of NRG1 promoting resistance to ADT implies a role in tumor development or progression, which aligns with the definition of an oncogenic variant.

      Gene→Variant (gene-first): 8850:S7C

      Genes: 8850

      Variants: S7C

      CIViC paragraph-level PMC7472556 Predictive Oncogenic
    3. karim2001khoury 19 Feb 2026
      To gain insight into the potential clinical relevance of these findings, we examined NRG1 expression in a cohort of 43 patients with localized prostate cancer who underwent radical prostatectomy surgery, 23 of whom recei

      [Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 21

      Evidence Type(s): Diagnostic, Predictive

      Justification: Diagnostic: The passage discusses the detection of NRG1 expression in patients with localized prostate cancer, indicating its potential role in classifying or defining the disease based on the presence or absence of NRG1 staining. Predictive: The analysis includes a comparison of NRG1 expression in patients who received neoadjuvant ADT versus those who were hormonally intact, suggesting a correlation with treatment response.

      Gene→Variant (gene-first): 3084:S6 8850:S7

      Genes: 3084 8850

      Variants: S6 S7

      CIViC paragraph-level PMC7472556 Diagnostic Predictive
    4. karim2001khoury 19 Feb 2026
      Our earlier analysis of five canonical AR target genes suggested that NRG1 preserves tumor cell viability without restoring AR target gene expression (Figures 2G and 2H). To address this question more comprehensively, we

      [Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 19

      Evidence Type(s): None

      Justification: Not enough information in this passage.

      Gene→Variant (gene-first): 1956:S2 3084:S6C

      Genes: 1956 3084

      Variants: S2 S6C

      CIViC paragraph-level PMC7472556
    5. karim2001khoury 19 Feb 2026
      To carry out the purification, serum-free 22Pc-CAFCM was collected, concentrated, and applied to a Q-Superose anion exchange column, from which we eluted two protein peaks by using 30% and 100% high-salt buffer B (termed

      [Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses resistance-promoting activity and its correlation with HER3 phosphorylation, indicating a relationship with response or resistance to therapy. Functional: The passage describes how the variant affects HER3 phosphorylation activity, suggesting an alteration in molecular function related to resistance-promoting activity.

      Gene→Variant (gene-first): 5979:Q8

      Genes: 5979

      Variants: Q8

      CIViC paragraph-level PMC7472556 Predictive Functional
    6. karim2001khoury 19 Feb 2026
      To examine if upregulation of NRG1 is induced by hormone therapy, we treated freshly isolated primary CAFs from CWR22Pc tumors or pCAFs with CSS or Enz. CSS and Enz both induced NRG1 mRNA and protein expression after 7 d

      [Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 23

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses how NRG1 levels increase after androgen deprivation therapy (ADT) and suggests that these elevated levels are sufficient to promote resistance to ADT, indicating a correlation with treatment response. Oncogenic: The mention of NRG1 promoting resistance to ADT implies a role in tumor development or progression, which aligns with the definition of an oncogenic variant.

      Gene→Variant (gene-first): 8850:S7C

      Genes: 8850

      Variants: S7C

      CIViC paragraph-level PMC7472556 Predictive Oncogenic
    7. karim2001khoury 19 Feb 2026
      To gain insight into the potential clinical relevance of these findings, we examined NRG1 expression in a cohort of 43 patients with localized prostate cancer who underwent radical prostatectomy surgery, 23 of whom recei

      [Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 21

      Evidence Type(s): Diagnostic, Predictive

      Justification: Diagnostic: The passage discusses the detection of NRG1 expression in patients with localized prostate cancer, indicating its potential role in classifying or defining the disease based on the presence or absence of NRG1 staining. Predictive: The analysis includes a comparison of NRG1 expression in patients who received neoadjuvant ADT versus those who were hormonally intact, suggesting a correlation with treatment response.

      Gene→Variant (gene-first): 3084:S6 8850:S7

      Genes: 3084 8850

      Variants: S6 S7

      CIViC paragraph-level PMC7472556 Diagnostic Predictive
    8. karim2001khoury 19 Feb 2026
      Our earlier analysis of five canonical AR target genes suggested that NRG1 preserves tumor cell viability without restoring AR target gene expression (Figures 2G and 2H). To address this question more comprehensively, we

      [Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 19

      Evidence Type(s): None

      Justification: Not enough information in this passage.

      Gene→Variant (gene-first): 1956:S2 3084:S6C

      Genes: 1956 3084

      Variants: S2 S6C

      CIViC paragraph-level PMC7472556
    9. karim2001khoury 19 Feb 2026
      To carry out the purification, serum-free 22Pc-CAFCM was collected, concentrated, and applied to a Q-Superose anion exchange column, from which we eluted two protein peaks by using 30% and 100% high-salt buffer B (termed

      [Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses resistance-promoting activity and its correlation with HER3 phosphorylation, indicating a relationship with response or resistance to therapy. Functional: The passage describes how the variant affects HER3 phosphorylation activity, suggesting an alteration in molecular function related to resistance-promoting activity.

      Gene→Variant (gene-first): 5979:Q8

      Genes: 5979

      Variants: Q8

      CIViC paragraph-level PMC7472556 Predictive Functional
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    pmc.ncbi.nlm.nih.gov/articles/PMC7472556/pdf/nihms-1620953.pdf