Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma
Abstract The genomic instability (GI) /homologous recombination deficiency (HRD) score, calculated as the sum of the events of loss of heterozygosity (LOH), large-scale state transition (LST) and telomere allele imbalance (TAI), is used to guide the choice of treatment in several cancers, but its re...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-10-01
|
| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-023-00465-x |
| _version_ | 1827770823191035904 |
|---|---|
| author | Juan Feng Yang Lan Feng Liu Ye Yuan Jia Ge Sen Wei Hu Luo Jianjun Li Tao Luo Xiuwu Bian |
| author_facet | Juan Feng Yang Lan Feng Liu Ye Yuan Jia Ge Sen Wei Hu Luo Jianjun Li Tao Luo Xiuwu Bian |
| author_sort | Juan Feng |
| collection | DOAJ |
| description | Abstract The genomic instability (GI) /homologous recombination deficiency (HRD) score, calculated as the sum of the events of loss of heterozygosity (LOH), large-scale state transition (LST) and telomere allele imbalance (TAI), is used to guide the choice of treatment in several cancers, but its relationship with genomic features, clinicopathological characteristics and prognosis in lung cancer is poorly understood, which could lead to population bias in prospective studies. We retrospectively analyzed 1011 lung cancer patients whose tumor samples were successfully profiled by high-throughput sequencing panel including GI/HRD score. Alterations of many cancer suppressor genes were associated with higher GI/HRD scores, biallelic inactivation of TP53 was correlated with a high GI/HRD score. A combination of two gene alterations exhibited a higher GI/HRD scores than single gene alterations. The GI/HRD score was associated with advanced stages in lung adenocarcinoma but not in lung squamous cell carcinoma. Furthermore, patients with higher GI/HRD scores had significantly shorter overall survival and progression-free survival than patients with lower GI/HRD scores. Finally, patients with a combination of a higher GI/HRD scores and TP53 alteration exhibited an extremely poor prognosis compared with patients with a lower GI/HRD scores and wild-type TP53 (overall survival, training cohort, hazard ratio (HR) = 8.56, P < 0.001; validation cohort, HR = 6.47, P < 0.001; progression-free survival, HR = 4.76, P < 0.001). Our study revealed the prognostic value of the GI/HRD score in lung adenocarcinoma, but not for all lung cancer. Moreover, the combination of the GI/HRD score and TP53 status could be a promising strategy to predict the prognosis of patients with lung adenocarcinoma. |
| first_indexed | 2024-03-11T12:44:59Z |
| format | Article |
| id | doaj.art-b0add211e2dd4f67b47446effcf67aee |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-11T12:44:59Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-b0add211e2dd4f67b47446effcf67aee2023-11-05T12:06:20ZengNature Portfolionpj Precision Oncology2397-768X2023-10-01711910.1038/s41698-023-00465-xCombination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinomaJuan Feng0Yang Lan1Feng Liu2Ye Yuan3Jia Ge4Sen Wei5Hu Luo6Jianjun Li7Tao Luo8Xiuwu Bian9Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of ChinaDepartment of Respiratory and Critical Care Medicine, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University)Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of ChinaAbstract The genomic instability (GI) /homologous recombination deficiency (HRD) score, calculated as the sum of the events of loss of heterozygosity (LOH), large-scale state transition (LST) and telomere allele imbalance (TAI), is used to guide the choice of treatment in several cancers, but its relationship with genomic features, clinicopathological characteristics and prognosis in lung cancer is poorly understood, which could lead to population bias in prospective studies. We retrospectively analyzed 1011 lung cancer patients whose tumor samples were successfully profiled by high-throughput sequencing panel including GI/HRD score. Alterations of many cancer suppressor genes were associated with higher GI/HRD scores, biallelic inactivation of TP53 was correlated with a high GI/HRD score. A combination of two gene alterations exhibited a higher GI/HRD scores than single gene alterations. The GI/HRD score was associated with advanced stages in lung adenocarcinoma but not in lung squamous cell carcinoma. Furthermore, patients with higher GI/HRD scores had significantly shorter overall survival and progression-free survival than patients with lower GI/HRD scores. Finally, patients with a combination of a higher GI/HRD scores and TP53 alteration exhibited an extremely poor prognosis compared with patients with a lower GI/HRD scores and wild-type TP53 (overall survival, training cohort, hazard ratio (HR) = 8.56, P < 0.001; validation cohort, HR = 6.47, P < 0.001; progression-free survival, HR = 4.76, P < 0.001). Our study revealed the prognostic value of the GI/HRD score in lung adenocarcinoma, but not for all lung cancer. Moreover, the combination of the GI/HRD score and TP53 status could be a promising strategy to predict the prognosis of patients with lung adenocarcinoma.https://doi.org/10.1038/s41698-023-00465-x |
| spellingShingle | Juan Feng Yang Lan Feng Liu Ye Yuan Jia Ge Sen Wei Hu Luo Jianjun Li Tao Luo Xiuwu Bian Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma npj Precision Oncology |
| title | Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
| title_full | Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
| title_fullStr | Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
| title_full_unstemmed | Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
| title_short | Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
| title_sort | combination of genomic instability score and tp53 status for prognosis prediction in lung adenocarcinoma |
| url | https://doi.org/10.1038/s41698-023-00465-x |
| work_keys_str_mv | AT juanfeng combinationofgenomicinstabilityscoreandtp53statusforprognosispredictioninlungadenocarcinoma AT yanglan combinationofgenomicinstabilityscoreandtp53statusforprognosispredictioninlungadenocarcinoma AT fengliu combinationofgenomicinstabilityscoreandtp53statusforprognosispredictioninlungadenocarcinoma AT yeyuan combinationofgenomicinstabilityscoreandtp53statusforprognosispredictioninlungadenocarcinoma AT jiage combinationofgenomicinstabilityscoreandtp53statusforprognosispredictioninlungadenocarcinoma AT senwei combinationofgenomicinstabilityscoreandtp53statusforprognosispredictioninlungadenocarcinoma AT huluo combinationofgenomicinstabilityscoreandtp53statusforprognosispredictioninlungadenocarcinoma AT jianjunli combinationofgenomicinstabilityscoreandtp53statusforprognosispredictioninlungadenocarcinoma AT taoluo combinationofgenomicinstabilityscoreandtp53statusforprognosispredictioninlungadenocarcinoma AT xiuwubian combinationofgenomicinstabilityscoreandtp53statusforprognosispredictioninlungadenocarcinoma |