Genetic and immune microenvironment characterization of HER2-positive gastric cancer: Their association with response to trastuzumab-based treatment
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kwon, Hyun Jung | - |
dc.contributor.author | Park, Yujun | - |
dc.contributor.author | Nam, Soo Kyung | - |
dc.contributor.author | Kang, Enoch | - |
dc.contributor.author | Kim, Ka-Kyung | - |
dc.contributor.author | Jeong, Inhae | - |
dc.contributor.author | Kwak, Yoonjin | - |
dc.contributor.author | Yoon, Jeesun | - |
dc.contributor.author | Kim, Tae-Yong | - |
dc.contributor.author | Lee, Keun-Wook | - |
dc.contributor.author | Oh, Do-Youn | - |
dc.contributor.author | Im, Seock-Ah | - |
dc.contributor.author | Kong, Seong-Ho | - |
dc.contributor.author | Park, Do Joong | - |
dc.contributor.author | Lee, Hyuk-Joon | - |
dc.contributor.author | Kim, Hyung-Ho | - |
dc.contributor.author | Yang, Han-Kwang | - |
dc.contributor.author | Lee, Hye Seung | - |
dc.date.accessioned | 2024-07-19T04:30:26Z | - |
dc.date.available | 2024-07-19T04:30:26Z | - |
dc.date.issued | 2023-05 | - |
dc.identifier.issn | 2045-7634 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/74988 | - |
dc.description.abstract | Background: We aimed to determine the molecular and immune microenvironment characteristics of HER2-positive gastric cancer (GC) related to the patient's response to first line trastuzumab- based treatment.Methods: Eighty three cases of HER2-positive advanced gastric adenocarcinoma patients treated with trastuzumab were enrolled. Targeted deep sequencing and transcriptome analysis were performed on selected 21 cases (exploration cohort) along with two post-treatment samples. The results were compared between patients progressed before 6 months (Group 2) and others (Group 1), and were validated by FISH and immunohistochemistry in total cohort. Tumor-infiltrating immune cells were evaluated using RNA sequencing data and multiplex immunohistochemistry. Progression free survival (PFS) analysis was performed.Results: Group 1 showed frequent amplification of G1/S cell cycle checkpoint related genes and upregulated KEGG pathways related to cell proliferation. In contrast, Group 2 had more frequent EGFR, HER3, and MET amplification and higher RNA expression in immune-related KEGG pathways than Group 1. In total cohort, significant predictors of better PFS were cell cycle-related including CCNE1 amplification, Cyclin A and PLK1 overexpression, and decreased Cyclin D3 and HER3 expression (p < 0.05), or immune-related including high density of CD3(-)CD57(+) NK cells and PD -L1 combined positive score >= 5 (p < 0.05). The best prognostic predictors were a combination of Cyclin A, Cyclin E, p21, and HER3 (p < 0.001).Conclusion: HER2-positive GC with favorable response to trastuzumab were characterized by cell cycle-related gene alterations and increased CD3-CD57+ NK cell infiltration. These findings would be helpful to the fine modulation of therapeutic strategies for patients with HER2-positive GC. | - |
dc.format.extent | 14 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | WILEY | - |
dc.title | Genetic and immune microenvironment characterization of HER2-positive gastric cancer: Their association with response to trastuzumab-based treatment | - |
dc.type | Article | - |
dc.identifier.doi | 10.1002/cam4.5769 | - |
dc.identifier.bibliographicCitation | CANCER MEDICINE, v.12, no.9, pp 10371 - 10384 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.wosid | 000952910000001 | - |
dc.identifier.scopusid | 2-s2.0-85150624556 | - |
dc.citation.endPage | 10384 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 10371 | - |
dc.citation.title | CANCER MEDICINE | - |
dc.citation.volume | 12 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | cell cycle | - |
dc.subject.keywordAuthor | HER2-positive gastric cancer | - |
dc.subject.keywordAuthor | NK cell | - |
dc.subject.keywordAuthor | PD-L1 | - |
dc.subject.keywordAuthor | trastuzumab | - |
dc.subject.keywordPlus | DEPENDENT CELLULAR CYTOTOXICITY | - |
dc.subject.keywordPlus | NATURAL-KILLER-CELLS | - |
dc.subject.keywordPlus | CYCLIN-E | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | AMPLIFICATION | - |
dc.subject.keywordPlus | SENSITIVITY | - |
dc.subject.keywordPlus | BIOMARKERS | - |
dc.subject.keywordPlus | THERAPIES | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea (06974)02-820-6194
COPYRIGHT 2019 Chung-Ang University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.