Thejus Jayakrishnan, Yasmine Baca, Joanne Xiu, Mehrie Patel, Benjamin A Weinberg, Emil Lou, Jashodeep Datta, Moh'd Khushman, Pat Gulhati, Sanjay Goel, Tiago Biachi de Castria, Vaia Florou, Kanika G Nair, Suneel D Kamath, Alok A Khorana
{"title":"早发胆道癌与一般发病胆道癌的分子差异及其治疗意义","authors":"Thejus Jayakrishnan, Yasmine Baca, Joanne Xiu, Mehrie Patel, Benjamin A Weinberg, Emil Lou, Jashodeep Datta, Moh'd Khushman, Pat Gulhati, Sanjay Goel, Tiago Biachi de Castria, Vaia Florou, Kanika G Nair, Suneel D Kamath, Alok A Khorana","doi":"10.1200/PO.24.00138","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Early-onset biliary tract cancer (eoBTC) is among the fast-growing subset of early-onset cancers, yet little is known about its biology. We sought to identify novel molecular characteristics of eoBTC in relation to average-onset BTC (aoBTC) using a real-world multiomics data set.</p><p><strong>Methods: </strong>The study comprised patients with BTC whose tumors underwent molecular analyses at Caris Life Sciences and were categorized by age (<50 years for eoBTC, ≥50 years for aoBTC). <i>P</i> values were adjusted for multiple testing and considered significant at <i>Q</i> < 0.05 (molecular comparisons) or <i>Q</i> < 0.25 (Gene Set Enrichment Analysis [GSEA]). Insurance claims data were used for survival analysis.</p><p><strong>Results: </strong>The study included 5,587 patients with BTC (453 eoBTC, median age = 44 years and 5,134 aoBTC, median age = 68 years). <i>FGFR2</i> fusion (15.7% in eoBTC <i>v</i> 5.9% in aoBTC) and <i>NIPBL</i> fusion (1.1% <i>v</i> 0%) were significantly more prevalent in eoBTC (both <i>Q</i> < 0.001). The interferon gamma-IFG score (fold change [FC], 1.1; <i>Q</i> = 0.01) and T-cell inflammation score (FC, 17.3; <i>Q</i> = 0.03) were significantly higher in aoBTC. On GSEA, angiogenesis was enriched in eoBTC (normalized enrichment score [NES] = 1.51; <i>Q</i> = 0.16), whereas IFG (NES = -1.58; <i>Q</i> = 0.06) and inflammatory response (NES = -1.46; <i>Q</i> = 0.18) were enriched in aoBTC. The median overall survival (OS) was 16.5 (eoBTC) versus 13.3 months (aoBTC), hazard ratio = 0.86, <i>P</i> = .004. The median OS by FGFR2 fusion (with fusion <i>v</i> without) was 21.7 versus 15.0 months (<i>P</i> = .47) for eoBTC and 18.6 versus 12.2 months (<i>P</i> < .001) for aoBTC.</p><p><strong>Conclusion: </strong>We identified crucial differences including higher prevalence of <i>FGFR2</i> fusions in eoBTC and variations in immunotherapy-related markers. Better outcomes in eoBTC were affected by the <i>FGFR2</i> fusion status. Our findings underscore the need for ensuring access to next-generation sequencing testing, including prompt identification of actionable targets.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400138"},"PeriodicalIF":5.3000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Molecular Differences With Therapeutic Implications in Early-Onset Compared With Average-Onset Biliary Tract Cancers.\",\"authors\":\"Thejus Jayakrishnan, Yasmine Baca, Joanne Xiu, Mehrie Patel, Benjamin A Weinberg, Emil Lou, Jashodeep Datta, Moh'd Khushman, Pat Gulhati, Sanjay Goel, Tiago Biachi de Castria, Vaia Florou, Kanika G Nair, Suneel D Kamath, Alok A Khorana\",\"doi\":\"10.1200/PO.24.00138\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Early-onset biliary tract cancer (eoBTC) is among the fast-growing subset of early-onset cancers, yet little is known about its biology. We sought to identify novel molecular characteristics of eoBTC in relation to average-onset BTC (aoBTC) using a real-world multiomics data set.</p><p><strong>Methods: </strong>The study comprised patients with BTC whose tumors underwent molecular analyses at Caris Life Sciences and were categorized by age (<50 years for eoBTC, ≥50 years for aoBTC). <i>P</i> values were adjusted for multiple testing and considered significant at <i>Q</i> < 0.05 (molecular comparisons) or <i>Q</i> < 0.25 (Gene Set Enrichment Analysis [GSEA]). Insurance claims data were used for survival analysis.</p><p><strong>Results: </strong>The study included 5,587 patients with BTC (453 eoBTC, median age = 44 years and 5,134 aoBTC, median age = 68 years). <i>FGFR2</i> fusion (15.7% in eoBTC <i>v</i> 5.9% in aoBTC) and <i>NIPBL</i> fusion (1.1% <i>v</i> 0%) were significantly more prevalent in eoBTC (both <i>Q</i> < 0.001). The interferon gamma-IFG score (fold change [FC], 1.1; <i>Q</i> = 0.01) and T-cell inflammation score (FC, 17.3; <i>Q</i> = 0.03) were significantly higher in aoBTC. On GSEA, angiogenesis was enriched in eoBTC (normalized enrichment score [NES] = 1.51; <i>Q</i> = 0.16), whereas IFG (NES = -1.58; <i>Q</i> = 0.06) and inflammatory response (NES = -1.46; <i>Q</i> = 0.18) were enriched in aoBTC. The median overall survival (OS) was 16.5 (eoBTC) versus 13.3 months (aoBTC), hazard ratio = 0.86, <i>P</i> = .004. The median OS by FGFR2 fusion (with fusion <i>v</i> without) was 21.7 versus 15.0 months (<i>P</i> = .47) for eoBTC and 18.6 versus 12.2 months (<i>P</i> < .001) for aoBTC.</p><p><strong>Conclusion: </strong>We identified crucial differences including higher prevalence of <i>FGFR2</i> fusions in eoBTC and variations in immunotherapy-related markers. Better outcomes in eoBTC were affected by the <i>FGFR2</i> fusion status. Our findings underscore the need for ensuring access to next-generation sequencing testing, including prompt identification of actionable targets.</p>\",\"PeriodicalId\":14797,\"journal\":{\"name\":\"JCO precision oncology\",\"volume\":\"8 \",\"pages\":\"e2400138\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JCO precision oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/PO.24.00138\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCO precision oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/PO.24.00138","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Molecular Differences With Therapeutic Implications in Early-Onset Compared With Average-Onset Biliary Tract Cancers.
Purpose: Early-onset biliary tract cancer (eoBTC) is among the fast-growing subset of early-onset cancers, yet little is known about its biology. We sought to identify novel molecular characteristics of eoBTC in relation to average-onset BTC (aoBTC) using a real-world multiomics data set.
Methods: The study comprised patients with BTC whose tumors underwent molecular analyses at Caris Life Sciences and were categorized by age (<50 years for eoBTC, ≥50 years for aoBTC). P values were adjusted for multiple testing and considered significant at Q < 0.05 (molecular comparisons) or Q < 0.25 (Gene Set Enrichment Analysis [GSEA]). Insurance claims data were used for survival analysis.
Results: The study included 5,587 patients with BTC (453 eoBTC, median age = 44 years and 5,134 aoBTC, median age = 68 years). FGFR2 fusion (15.7% in eoBTC v 5.9% in aoBTC) and NIPBL fusion (1.1% v 0%) were significantly more prevalent in eoBTC (both Q < 0.001). The interferon gamma-IFG score (fold change [FC], 1.1; Q = 0.01) and T-cell inflammation score (FC, 17.3; Q = 0.03) were significantly higher in aoBTC. On GSEA, angiogenesis was enriched in eoBTC (normalized enrichment score [NES] = 1.51; Q = 0.16), whereas IFG (NES = -1.58; Q = 0.06) and inflammatory response (NES = -1.46; Q = 0.18) were enriched in aoBTC. The median overall survival (OS) was 16.5 (eoBTC) versus 13.3 months (aoBTC), hazard ratio = 0.86, P = .004. The median OS by FGFR2 fusion (with fusion v without) was 21.7 versus 15.0 months (P = .47) for eoBTC and 18.6 versus 12.2 months (P < .001) for aoBTC.
Conclusion: We identified crucial differences including higher prevalence of FGFR2 fusions in eoBTC and variations in immunotherapy-related markers. Better outcomes in eoBTC were affected by the FGFR2 fusion status. Our findings underscore the need for ensuring access to next-generation sequencing testing, including prompt identification of actionable targets.
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