The association of genomic alterations with PD‐L1 expression in Chinese patients with EGFR/ALK wild‐type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapy
Abstract Background The study focuses on PD‐L1 expression as an essential biomarker for gauging the response of EGFR/ALK wild‐type NSCLC patients to FDA‐approved immune checkpoint inhibitors (ICIs). It aims to explore clinical, molecular, and immune microenvironment characteristics associated with P...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.7038 |
| _version_ | 1797217004824821760 |
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| author | Fangfang Liu Xuemei Zhang Mengyao Lu Chun Liu Xiaodong Zhang Qian Chu Yuan Chen Peng Zhang |
| author_facet | Fangfang Liu Xuemei Zhang Mengyao Lu Chun Liu Xiaodong Zhang Qian Chu Yuan Chen Peng Zhang |
| author_sort | Fangfang Liu |
| collection | DOAJ |
| description | Abstract Background The study focuses on PD‐L1 expression as an essential biomarker for gauging the response of EGFR/ALK wild‐type NSCLC patients to FDA‐approved immune checkpoint inhibitors (ICIs). It aims to explore clinical, molecular, and immune microenvironment characteristics associated with PD‐L1 expression in EGFR/ALK wild‐type lung adenocarcinoma patients eligible for ICI therapy. Methods In this retrospective study, tumor samples from 359 Chinese EGFR/ALK wild‐type lung adenocarcinoma patients underwent comprehensive evaluations for PD‐L1 expression and NGS‐targeted sequencing. The investigation encompassed the analysis and comparison of clinical traits, gene mutations, pathways, and immune signatures between two groups categorized by PD‐L1 status: negative (TPS < 1%) and positive (TPS ≥ 1%). Additionally, the study explored the link between genomic changes and outcomes following immunotherapy. Results High tumor mutational burden correlated significantly with PD‐L1 positivity in patients with EGFR/ALK wild‐type lung adenocarcinoma. Gene alterations, including TP53, KRAS, and others, were more pronounced in the PD‐L1 positive group. Pathway analysis highlighted higher frequencies of alterations in pathways like RTK/RAS, p53, and Hippo in PD‐L1‐positive patients. The Hippo pathway's relevance was confirmed in separate immunotherapy cohorts, associated with better outcomes. In terms of immune cell infiltration, Hippo mutants exhibited higher levels of CD68+PD‐L1+ macrophages, CD8+ T cells, and CD8+PD‐1− T cells. Conclusions This study offers insights into genomic features of Chinese EGFR/ALK wild‐type lung adenocarcinoma patients based on PD‐L1 expression. Notably, Hippo pathway alterations were linked to improved immunotherapy outcomes. These findings suggest connections between the Hippo pathway and PD‐L1 expression, warranting further clinical and functional investigations. The research advances our understanding of PD‐L1 expression's genomic context and immunotherapy response in EGFR/ALK wild‐type lung adenocarcinoma. |
| first_indexed | 2024-03-07T15:44:05Z |
| format | Article |
| id | doaj.art-f3282c6fdb3a447a875c0a52c02351c2 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-24T11:54:58Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-f3282c6fdb3a447a875c0a52c02351c22024-04-09T05:45:47ZengWileyCancer Medicine2045-76342024-02-01133n/an/a10.1002/cam4.7038The association of genomic alterations with PD‐L1 expression in Chinese patients with EGFR/ALK wild‐type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapyFangfang Liu0Xuemei Zhang1Mengyao Lu2Chun Liu3Xiaodong Zhang4Qian Chu5Yuan Chen6Peng Zhang7Department of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaGenecast Biotechnology Co., Ltd Wuxi Jiangsu ChinaGenecast Biotechnology Co., Ltd Wuxi Jiangsu ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaAbstract Background The study focuses on PD‐L1 expression as an essential biomarker for gauging the response of EGFR/ALK wild‐type NSCLC patients to FDA‐approved immune checkpoint inhibitors (ICIs). It aims to explore clinical, molecular, and immune microenvironment characteristics associated with PD‐L1 expression in EGFR/ALK wild‐type lung adenocarcinoma patients eligible for ICI therapy. Methods In this retrospective study, tumor samples from 359 Chinese EGFR/ALK wild‐type lung adenocarcinoma patients underwent comprehensive evaluations for PD‐L1 expression and NGS‐targeted sequencing. The investigation encompassed the analysis and comparison of clinical traits, gene mutations, pathways, and immune signatures between two groups categorized by PD‐L1 status: negative (TPS < 1%) and positive (TPS ≥ 1%). Additionally, the study explored the link between genomic changes and outcomes following immunotherapy. Results High tumor mutational burden correlated significantly with PD‐L1 positivity in patients with EGFR/ALK wild‐type lung adenocarcinoma. Gene alterations, including TP53, KRAS, and others, were more pronounced in the PD‐L1 positive group. Pathway analysis highlighted higher frequencies of alterations in pathways like RTK/RAS, p53, and Hippo in PD‐L1‐positive patients. The Hippo pathway's relevance was confirmed in separate immunotherapy cohorts, associated with better outcomes. In terms of immune cell infiltration, Hippo mutants exhibited higher levels of CD68+PD‐L1+ macrophages, CD8+ T cells, and CD8+PD‐1− T cells. Conclusions This study offers insights into genomic features of Chinese EGFR/ALK wild‐type lung adenocarcinoma patients based on PD‐L1 expression. Notably, Hippo pathway alterations were linked to improved immunotherapy outcomes. These findings suggest connections between the Hippo pathway and PD‐L1 expression, warranting further clinical and functional investigations. The research advances our understanding of PD‐L1 expression's genomic context and immunotherapy response in EGFR/ALK wild‐type lung adenocarcinoma.https://doi.org/10.1002/cam4.7038adenocarcinomaHippoimmunotherapyNSCLCPD‐L1tumor immune microenvironment |
| spellingShingle | Fangfang Liu Xuemei Zhang Mengyao Lu Chun Liu Xiaodong Zhang Qian Chu Yuan Chen Peng Zhang The association of genomic alterations with PD‐L1 expression in Chinese patients with EGFR/ALK wild‐type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapy Cancer Medicine adenocarcinoma Hippo immunotherapy NSCLC PD‐L1 tumor immune microenvironment |
| title | The association of genomic alterations with PD‐L1 expression in Chinese patients with EGFR/ALK wild‐type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapy |
| title_full | The association of genomic alterations with PD‐L1 expression in Chinese patients with EGFR/ALK wild‐type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapy |
| title_fullStr | The association of genomic alterations with PD‐L1 expression in Chinese patients with EGFR/ALK wild‐type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapy |
| title_full_unstemmed | The association of genomic alterations with PD‐L1 expression in Chinese patients with EGFR/ALK wild‐type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapy |
| title_short | The association of genomic alterations with PD‐L1 expression in Chinese patients with EGFR/ALK wild‐type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapy |
| title_sort | association of genomic alterations with pd l1 expression in chinese patients with egfr alk wild type lung adenocarcinoma and potential predictive value of hippo pathway mutations to immunotherapy |
| topic | adenocarcinoma Hippo immunotherapy NSCLC PD‐L1 tumor immune microenvironment |
| url | https://doi.org/10.1002/cam4.7038 |
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