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Genomic events stratifying prognosis of early gastric cancer

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Titel: Genomic events stratifying prognosis of early gastric cancer
Autoren: Molinari C., Solaini L., Rebuzzi F., Tedaldi G., Angeli D., Petracci E., Prascevic D., Ewald J., Rahm E., Canale M., Giovanni M., Tomezzoli A., Bencivenga M., Ambrosio M. R., Marrelli D., Morgagni P., Ercolani G., Ulivi P., Saragoni L.
Quelle: Gastric Cancer
Verlagsinformationen: Springer Science and Business Media LLC, 2024.
Publikationsjahr: 2024
Schlagwörter: Male, Adult, 0301 basic medicine, LRP1B, 03 medical and health sciences, Stomach Neoplasms, ARID1A, EGC, Pen, Prognosis, Biomarkers, Tumor, Humans, Aged, Aged, 80 and over, 0303 health sciences, Genomics, Middle Aged, DNA-Binding Proteins, Receptors, LDL, Aged, 80 and over [MeSH], Aged [MeSH], Transcription Factors/genetics [MeSH], Stomach Neoplasms/pathology [MeSH], Stomach Neoplasms/surgery [MeSH], Neoplasm Recurrence, Local/pathology [MeSH], Stomach Neoplasms/mortality [MeSH], DNA-Binding Proteins/genetics [MeSH], Original Article, Male [MeSH], Neoplasm Recurrence, Local/genetics [MeSH], Stomach Neoplasms/genetics [MeSH], Female [MeSH], Follow-Up Studies [MeSH], Mutation [MeSH], Adult [MeSH], Humans [MeSH], Genomics/methods [MeSH], Middle Aged [MeSH], Microsatellite Instability [MeSH], Receptors, LDL [MeSH], Biomarkers, Tumor/genetics [MeSH], Prognosis [MeSH], Mutation, Female, Microsatellite Instability, Neoplasm Recurrence, Local, Transcription Factors, Follow-Up Studies
Beschreibung: Background The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses. Methods Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort. Results Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093). Conclusions We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients.
Publikationsart: Article
Other literature type
Dateibeschreibung: application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document
Sprache: English
ISSN: 1436-3305
1436-3291
DOI: 10.1007/s10120-024-01536-z
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/39028418
https://repository.publisso.de/resource/frl:6492499
https://link.springer.com/article/10.1007/s10120-024-01536-z
https://doi.org/10.1007/s10120-024-01536-z
https://hdl.handle.net/11585/1001645
Rights: CC BY
Dokumentencode: edsair.doi.dedup.....e17b04d467535e9a4494a7efdb930a34
Datenbank: OpenAIRE
Beschreibung
Abstract:Background The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses. Methods Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort. Results Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093). Conclusions We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients.
ISSN:14363305
14363291
DOI:10.1007/s10120-024-01536-z