FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4367856204> ?p ?o ?g. }

• W4367856204 endingPage "428.e7" @default.
• W4367856204 startingPage "414" @default.
• W4367856204 abstract "Background & AimsTumor genetic testing is indispensable in the management of primary and metastatic colorectal cancer (CRC), yet the indications for genomics-guided precision medicine and immunotherapy must be better understood and defined.MethodsWe prospectively sequenced tumors from 869 Chinese patients with CRC by a large panel and evaluated the clinical significance of single-gene somatic mutations and co-occurring events in metastatic CRC, as well as their functional effects and tumorigenic mechanisms. We systematically assessed the heterogeneity of the tumor immune microenvironment in different genomic contexts through the combined analysis of Immunoscore, multiplex immunostaining, whole-exome sequencing, transcriptome, and single-cell sequencing.ResultsSingle-gene somatic mutations in BRAF or RBM10 were associated with shorter progression-free survival in patients with metastatic CRC. Functional studies suggested RBM10 acts as a tumor suppressor in CRC development. Co-mutations of KRAS/AMER1 or KRAS/APC were enriched in the metastatic cohort, which had poor progression-free survival and did not benefit from bevacizumab due to accelerated drug metabolism. Forty patients (4.6%) carried pathogenic or likely pathogenic germline alterations in the DNA damage repair pathway and 37.5% of these tumors had secondary-hit events with loss of heterozygosity or biallelic alterations. A high tumor insertion or deletion burden with high microsatellite instability suggested immunogenicity with numerous activated tumor-infiltrating lymphocytes, whereas polymerase epsilon exonuclease mutation with ultrahigh tumor mutation burden indicated a relatively quiescent immunophenotype. The heterogeneous genomic–immunologic interactions were reflected in the divergent neoantigen presentation and depletion, immune checkpoint expression, PD-1/PD-L1 interaction, and T-cell responsiveness to pembrolizumab.ConclusionsOur integrated analysis provides insights into CRC prognostic stratification, drug response, and personalized genomics–guided targeted and immunotherapies. Tumor genetic testing is indispensable in the management of primary and metastatic colorectal cancer (CRC), yet the indications for genomics-guided precision medicine and immunotherapy must be better understood and defined. We prospectively sequenced tumors from 869 Chinese patients with CRC by a large panel and evaluated the clinical significance of single-gene somatic mutations and co-occurring events in metastatic CRC, as well as their functional effects and tumorigenic mechanisms. We systematically assessed the heterogeneity of the tumor immune microenvironment in different genomic contexts through the combined analysis of Immunoscore, multiplex immunostaining, whole-exome sequencing, transcriptome, and single-cell sequencing. Single-gene somatic mutations in BRAF or RBM10 were associated with shorter progression-free survival in patients with metastatic CRC. Functional studies suggested RBM10 acts as a tumor suppressor in CRC development. Co-mutations of KRAS/AMER1 or KRAS/APC were enriched in the metastatic cohort, which had poor progression-free survival and did not benefit from bevacizumab due to accelerated drug metabolism. Forty patients (4.6%) carried pathogenic or likely pathogenic germline alterations in the DNA damage repair pathway and 37.5% of these tumors had secondary-hit events with loss of heterozygosity or biallelic alterations. A high tumor insertion or deletion burden with high microsatellite instability suggested immunogenicity with numerous activated tumor-infiltrating lymphocytes, whereas polymerase epsilon exonuclease mutation with ultrahigh tumor mutation burden indicated a relatively quiescent immunophenotype. The heterogeneous genomic–immunologic interactions were reflected in the divergent neoantigen presentation and depletion, immune checkpoint expression, PD-1/PD-L1 interaction, and T-cell responsiveness to pembrolizumab. Our integrated analysis provides insights into CRC prognostic stratification, drug response, and personalized genomics–guided targeted and immunotherapies." @default.
• W4367856204 created "2023-05-04" @default.
• W4367856204 creator A5010765759 @default.
• W4367856204 creator A5023547621 @default.
• W4367856204 creator A5024176882 @default.
• W4367856204 creator A5029322489 @default.
• W4367856204 creator A5041577726 @default.
• W4367856204 creator A5042141577 @default.
• W4367856204 creator A5060052210 @default.
• W4367856204 creator A5061605906 @default.
• W4367856204 creator A5079128498 @default.
• W4367856204 creator A5079595789 @default.
• W4367856204 creator A5079714227 @default.
• W4367856204 creator A5084082326 @default.
• W4367856204 date "2023-08-01" @default.
• W4367856204 modified "2023-10-14" @default.
• W4367856204 title "Molecular Profiling Provides Clinical Insights Into Targeted and Immunotherapies as Well as Colorectal Cancer Prognosis" @default.
• W4367856204 cites W2061132293 @default.
• W4367856204 cites W2095201384 @default.
• W4367856204 cites W2121847974 @default.
• W4367856204 cites W2129998117 @default.
• W4367856204 cites W2159429807 @default.
• W4367856204 cites W2170226272 @default.
• W4367856204 cites W2262414037 @default.
• W4367856204 cites W2310046094 @default.
• W4367856204 cites W2538201653 @default.
• W4367856204 cites W2567103208 @default.
• W4367856204 cites W2597802455 @default.
• W4367856204 cites W2725858612 @default.
• W4367856204 cites W2739132742 @default.
• W4367856204 cites W2741253009 @default.
• W4367856204 cites W2783494975 @default.
• W4367856204 cites W2787981425 @default.
• W4367856204 cites W2889646458 @default.
• W4367856204 cites W2924359886 @default.
• W4367856204 cites W2950945543 @default.
• W4367856204 cites W2983284890 @default.
• W4367856204 cites W2987116731 @default.
• W4367856204 cites W3009139795 @default.
• W4367856204 cites W3018585354 @default.
• W4367856204 cites W3081768459 @default.
• W4367856204 cites W3083986479 @default.
• W4367856204 cites W3086302274 @default.
• W4367856204 cites W3090808618 @default.
• W4367856204 cites W3094399836 @default.
• W4367856204 cites W3098138586 @default.
• W4367856204 cites W3110672426 @default.
• W4367856204 cites W3134887329 @default.
• W4367856204 cites W3148370335 @default.
• W4367856204 cites W4223510971 @default.
• W4367856204 doi "https://doi.org/10.1053/j.gastro.2023.04.029" @default.
• W4367856204 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37146911" @default.
• W4367856204 hasPublicationYear "2023" @default.
• W4367856204 type Work @default.
• W4367856204 citedByCount "0" @default.
• W4367856204 crossrefType "journal-article" @default.
• W4367856204 hasAuthorship W4367856204A5010765759 @default.
• W4367856204 hasAuthorship W4367856204A5023547621 @default.
• W4367856204 hasAuthorship W4367856204A5024176882 @default.
• W4367856204 hasAuthorship W4367856204A5029322489 @default.
• W4367856204 hasAuthorship W4367856204A5041577726 @default.
• W4367856204 hasAuthorship W4367856204A5042141577 @default.
• W4367856204 hasAuthorship W4367856204A5060052210 @default.
• W4367856204 hasAuthorship W4367856204A5061605906 @default.
• W4367856204 hasAuthorship W4367856204A5079128498 @default.
• W4367856204 hasAuthorship W4367856204A5079595789 @default.
• W4367856204 hasAuthorship W4367856204A5079714227 @default.
• W4367856204 hasAuthorship W4367856204A5084082326 @default.
• W4367856204 hasBestOaLocation W43678562041 @default.
• W4367856204 hasConcept C104317684 @default.
• W4367856204 hasConcept C121608353 @default.
• W4367856204 hasConcept C13514818 @default.
• W4367856204 hasConcept C143589142 @default.
• W4367856204 hasConcept C16671776 @default.
• W4367856204 hasConcept C180754005 @default.
• W4367856204 hasConcept C21790070 @default.
• W4367856204 hasConcept C2777701055 @default.
• W4367856204 hasConcept C2779767149 @default.
• W4367856204 hasConcept C2781187634 @default.
• W4367856204 hasConcept C29906990 @default.
• W4367856204 hasConcept C501734568 @default.
• W4367856204 hasConcept C502942594 @default.
• W4367856204 hasConcept C526805850 @default.
• W4367856204 hasConcept C54355233 @default.
• W4367856204 hasConcept C60748783 @default.
• W4367856204 hasConcept C61320498 @default.
• W4367856204 hasConcept C86803240 @default.
• W4367856204 hasConceptScore W4367856204C104317684 @default.
• W4367856204 hasConceptScore W4367856204C121608353 @default.
• W4367856204 hasConceptScore W4367856204C13514818 @default.
• W4367856204 hasConceptScore W4367856204C143589142 @default.
• W4367856204 hasConceptScore W4367856204C16671776 @default.
• W4367856204 hasConceptScore W4367856204C180754005 @default.
• W4367856204 hasConceptScore W4367856204C21790070 @default.
• W4367856204 hasConceptScore W4367856204C2777701055 @default.
• W4367856204 hasConceptScore W4367856204C2779767149 @default.
• W4367856204 hasConceptScore W4367856204C2781187634 @default.
• W4367856204 hasConceptScore W4367856204C29906990 @default.

• next