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Genomic events stratifying prognosis of early gastric cancer.
Molinari, Chiara; Solaini, Leonardo; Rebuzzi, Francesca; Tedaldi, Gianluca; Angeli, Davide; Petracci, Elisabetta; Prascevic, Dusan; Ewald, Jan; Rahm, Erhard; Canale, Matteo; Giovanni, Martinelli; Tomezzoli, Anna; Bencivenga, Maria; Ambrosio, Maria Raffaella; Marrelli, Daniele; Morgagni, Paolo; Ercolani, Giorgio; Ulivi, Paola; Saragoni, Luca.
Afiliación
  • Molinari C; Biosciences Laboratory, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, FC, Italy.
  • Solaini L; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. leonardo.solaini2@unibo.it.
  • Rebuzzi F; General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy. leonardo.solaini2@unibo.it.
  • Tedaldi G; Biosciences Laboratory, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, FC, Italy.
  • Angeli D; Biosciences Laboratory, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, FC, Italy.
  • Petracci E; Biostatistics and Clinical Trials Unit, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST), "Dino Amadori", Meldola, FC, Italy.
  • Prascevic D; Biostatistics and Clinical Trials Unit, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST), "Dino Amadori", Meldola, FC, Italy.
  • Ewald J; Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI), Dresden/Leipzig University, Humboldtstr. 25, 04105, Leipzig, Germany.
  • Rahm E; Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI), Dresden/Leipzig University, Humboldtstr. 25, 04105, Leipzig, Germany.
  • Canale M; Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI), Dresden/Leipzig University, Humboldtstr. 25, 04105, Leipzig, Germany.
  • Giovanni M; Biosciences Laboratory, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, FC, Italy.
  • Tomezzoli A; Department of Hematology and Sciences Oncology, Institute of Haematology "L. and A. Seràgnoli", S. Orsola University Hospital, Bologna, Italy.
  • Bencivenga M; Department of Pathology, University of Verona, Verona, Italy.
  • Ambrosio MR; Unit of Upper GI Surgery, University of Verona, Verona, Italy.
  • Marrelli D; Pathology Unit, University of Siena, Siena, Italy.
  • Morgagni P; Surgery Unit, University of Siena, Siena, Italy.
  • Ercolani G; General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy.
  • Ulivi P; General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy.
  • Saragoni L; Biosciences Laboratory, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, FC, Italy.
Gastric Cancer ; 27(6): 1189-1200, 2024 Nov.
Article en En | MEDLINE | ID: mdl-39028418
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Inestabilidad de Microsatélites / Mutación Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Gastric Cancer Asunto de la revista: GASTROENTEROLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Japón
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Inestabilidad de Microsatélites / Mutación Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Gastric Cancer Asunto de la revista: GASTROENTEROLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Japón