TP53 co-mutations in advanced lung adenocarcinoma: comparative bioinformatic analyses suggest ambivalent character on overall survival alongside KRAS, STK11 and KEAP1 mutations
BackgroundRecently, we could show that the co-mutations of KRAS + KEAP1, STK11 + KEAP1 and KRAS + STK11 + KEAP1 lead to a significantly shorter median overall survival (mOS) in patients with lung cancer across treatments by analyzing multiple dataset. TP53, a tumor suppressor gene, plays a crucial r...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1357583/full |
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| author | Armin Frille Myriam Boeschen Hubert Wirtz Mathias Stiller Hendrik Bläker Maximilian von Laffert |
| author_facet | Armin Frille Myriam Boeschen Hubert Wirtz Mathias Stiller Hendrik Bläker Maximilian von Laffert |
| author_sort | Armin Frille |
| collection | DOAJ |
| description | BackgroundRecently, we could show that the co-mutations of KRAS + KEAP1, STK11 + KEAP1 and KRAS + STK11 + KEAP1 lead to a significantly shorter median overall survival (mOS) in patients with lung cancer across treatments by analyzing multiple dataset. TP53, a tumor suppressor gene, plays a crucial role in regulating cell cycle progression. Its mutations occur in approximately 40-50% of non-small lung cancer (NSCLC). Co-occurrence of all four mentioned mutations has been a matter of debate for years. The aim of this study was to assess the distribution of these four mutations and the influence of the different co-mutational patterns on survival.MethodsWe present a comparative bioinformatic analysis and refer to data of 4,109 patients with lung adenocarcinoma (LUAD).ResultsMost of the mutations within the LUAD belong to TP53-only (29.0%), quadruple-negative (25.9%) and KRAS-only (13.4%). Whereas TP53-mutations seem to have protective effects in the context of further KEAP1- and KRAS + KEAP1-alterations (improved mOS), their role seems contrary if acquired in an already existing combination of mutations as KRAS + STK11, KRAS + STK11 + KEAP1 and STK11 + KEAP1. TP53 co-mutations had a negative influence on KRAS-only mutated LUAD (mOS reduced significantly by more than 30%).DiscussionThese data underline the need for complex mutational testing to estimate prognosis more accurately in patients with advanced LUAD. |
| first_indexed | 2024-04-24T05:52:32Z |
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| id | doaj.art-a3158136e83046d5a3cff5f8e1ece06f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2025-03-20T14:03:05Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a3158136e83046d5a3cff5f8e1ece06f2024-09-11T10:09:08ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-04-011410.3389/fonc.2024.13575831357583TP53 co-mutations in advanced lung adenocarcinoma: comparative bioinformatic analyses suggest ambivalent character on overall survival alongside KRAS, STK11 and KEAP1 mutationsArmin Frille0Myriam Boeschen1Hubert Wirtz2Mathias Stiller3Hendrik Bläker4Maximilian von Laffert5Department of Respiratory Medicine, Leipzig University, Leipzig, GermanyInstitute of Pathology, Leipzig University, Leipzig, GermanyDepartment of Respiratory Medicine, Leipzig University, Leipzig, GermanyInstitute of Pathology, Leipzig University, Leipzig, GermanyInstitute of Pathology, Leipzig University, Leipzig, GermanyInstitute of Pathology, Leipzig University, Leipzig, GermanyBackgroundRecently, we could show that the co-mutations of KRAS + KEAP1, STK11 + KEAP1 and KRAS + STK11 + KEAP1 lead to a significantly shorter median overall survival (mOS) in patients with lung cancer across treatments by analyzing multiple dataset. TP53, a tumor suppressor gene, plays a crucial role in regulating cell cycle progression. Its mutations occur in approximately 40-50% of non-small lung cancer (NSCLC). Co-occurrence of all four mentioned mutations has been a matter of debate for years. The aim of this study was to assess the distribution of these four mutations and the influence of the different co-mutational patterns on survival.MethodsWe present a comparative bioinformatic analysis and refer to data of 4,109 patients with lung adenocarcinoma (LUAD).ResultsMost of the mutations within the LUAD belong to TP53-only (29.0%), quadruple-negative (25.9%) and KRAS-only (13.4%). Whereas TP53-mutations seem to have protective effects in the context of further KEAP1- and KRAS + KEAP1-alterations (improved mOS), their role seems contrary if acquired in an already existing combination of mutations as KRAS + STK11, KRAS + STK11 + KEAP1 and STK11 + KEAP1. TP53 co-mutations had a negative influence on KRAS-only mutated LUAD (mOS reduced significantly by more than 30%).DiscussionThese data underline the need for complex mutational testing to estimate prognosis more accurately in patients with advanced LUAD.https://www.frontiersin.org/articles/10.3389/fonc.2024.1357583/fullNSCLClung adenocarcinomaKRASSTK11KEAP1TP53 |
| spellingShingle | Armin Frille Myriam Boeschen Hubert Wirtz Mathias Stiller Hendrik Bläker Maximilian von Laffert TP53 co-mutations in advanced lung adenocarcinoma: comparative bioinformatic analyses suggest ambivalent character on overall survival alongside KRAS, STK11 and KEAP1 mutations Frontiers in Oncology NSCLC lung adenocarcinoma KRAS STK11 KEAP1 TP53 |
| title | TP53 co-mutations in advanced lung adenocarcinoma: comparative bioinformatic analyses suggest ambivalent character on overall survival alongside KRAS, STK11 and KEAP1 mutations |
| title_full | TP53 co-mutations in advanced lung adenocarcinoma: comparative bioinformatic analyses suggest ambivalent character on overall survival alongside KRAS, STK11 and KEAP1 mutations |
| title_fullStr | TP53 co-mutations in advanced lung adenocarcinoma: comparative bioinformatic analyses suggest ambivalent character on overall survival alongside KRAS, STK11 and KEAP1 mutations |
| title_full_unstemmed | TP53 co-mutations in advanced lung adenocarcinoma: comparative bioinformatic analyses suggest ambivalent character on overall survival alongside KRAS, STK11 and KEAP1 mutations |
| title_short | TP53 co-mutations in advanced lung adenocarcinoma: comparative bioinformatic analyses suggest ambivalent character on overall survival alongside KRAS, STK11 and KEAP1 mutations |
| title_sort | tp53 co mutations in advanced lung adenocarcinoma comparative bioinformatic analyses suggest ambivalent character on overall survival alongside kras stk11 and keap1 mutations |
| topic | NSCLC lung adenocarcinoma KRAS STK11 KEAP1 TP53 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1357583/full |
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