KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus Pembrolizumab
Abstract KRAS is involved in the stability and expression of PD-L1. We investigated the expression of circulating mRNA (cmRNA) of KRAS4A and KRAS4B and the possible impact on progression-free survival (PFS) of patients with metastatic lung adenocarcinoma treated with immunotherapy. Patients without...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-48304-0 |
| _version_ | 1827603634741837824 |
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| author | Rita Chiari Silvia Palladino Rita Emili Mariagrazia De Lisa Donatella Sarti Vincenzo Catalano Mauro Magnani Francesco Graziano Annamaria Ruzzo |
| author_facet | Rita Chiari Silvia Palladino Rita Emili Mariagrazia De Lisa Donatella Sarti Vincenzo Catalano Mauro Magnani Francesco Graziano Annamaria Ruzzo |
| author_sort | Rita Chiari |
| collection | DOAJ |
| description | Abstract KRAS is involved in the stability and expression of PD-L1. We investigated the expression of circulating mRNA (cmRNA) of KRAS4A and KRAS4B and the possible impact on progression-free survival (PFS) of patients with metastatic lung adenocarcinoma treated with immunotherapy. Patients without driver mutations undergoing Pembrolizumab (P) or P plus chemotherapy (PC) were prospectively accrued for liquid biopsy analysis of KRAS4A, KRAS4B, and PD-L1 cmRNA. Both KRAS isoforms were also studied for association with PD-L1 cmRNA. Of 56 patients, 28 received P and 28 PC. Patients with high levels of both KRAS isoforms showed significantly better PFS. The median PFS for KRAS4A was 29 months (95% CI 22–29 months) and KRAS4B 24 months (95% CI 13–29 months), respectively. The median PFS of patients with low levels of both isoforms was 12 months (95% CI 6–15 months for KRAS4A and 95% CI 5–20 months for KRAS4B). High KRAS4A retained a significant positive association with PFS in the multivariate model. An exploratory analysis in treatment subgroups found a positive association between high KRAS4A and KRAS4B with PFS in patients treated with P. PD-L1 cmRNA was significantly higher in patients with high KRAS isoforms levels and this effect was pronounced for high KRAS4A carriers. KRAS4A deserves further investigation as a potential marker for defining patients who may benefit the most from immune checkpoint inhibitors therapy and improving personalized cancer immunotherapeutic strategies. |
| first_indexed | 2024-03-09T05:43:28Z |
| format | Article |
| id | doaj.art-b4159c9030cf4b2284065d6c08f9084c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T05:43:28Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b4159c9030cf4b2284065d6c08f9084c2023-12-03T12:23:38ZengNature PortfolioScientific Reports2045-23222023-11-0113111010.1038/s41598-023-48304-0KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus PembrolizumabRita Chiari0Silvia Palladino1Rita Emili2Mariagrazia De Lisa3Donatella Sarti4Vincenzo Catalano5Mauro Magnani6Francesco Graziano7Annamaria Ruzzo8Oncology Unit, AST1 Pesaro e UrbinoDepartment of Biomolecular Sciences, University of Urbino “Carlo Bo”Oncology Unit, AST1 Pesaro e UrbinoOncology Unit, AST1 Pesaro e UrbinoOncology Unit, AST1 Pesaro e UrbinoOncology Unit, AST1 Pesaro e UrbinoDepartment of Biomolecular Sciences, University of Urbino “Carlo Bo”Oncology Unit, AST1 Pesaro e UrbinoDepartment of Biomolecular Sciences, University of Urbino “Carlo Bo”Abstract KRAS is involved in the stability and expression of PD-L1. We investigated the expression of circulating mRNA (cmRNA) of KRAS4A and KRAS4B and the possible impact on progression-free survival (PFS) of patients with metastatic lung adenocarcinoma treated with immunotherapy. Patients without driver mutations undergoing Pembrolizumab (P) or P plus chemotherapy (PC) were prospectively accrued for liquid biopsy analysis of KRAS4A, KRAS4B, and PD-L1 cmRNA. Both KRAS isoforms were also studied for association with PD-L1 cmRNA. Of 56 patients, 28 received P and 28 PC. Patients with high levels of both KRAS isoforms showed significantly better PFS. The median PFS for KRAS4A was 29 months (95% CI 22–29 months) and KRAS4B 24 months (95% CI 13–29 months), respectively. The median PFS of patients with low levels of both isoforms was 12 months (95% CI 6–15 months for KRAS4A and 95% CI 5–20 months for KRAS4B). High KRAS4A retained a significant positive association with PFS in the multivariate model. An exploratory analysis in treatment subgroups found a positive association between high KRAS4A and KRAS4B with PFS in patients treated with P. PD-L1 cmRNA was significantly higher in patients with high KRAS isoforms levels and this effect was pronounced for high KRAS4A carriers. KRAS4A deserves further investigation as a potential marker for defining patients who may benefit the most from immune checkpoint inhibitors therapy and improving personalized cancer immunotherapeutic strategies.https://doi.org/10.1038/s41598-023-48304-0 |
| spellingShingle | Rita Chiari Silvia Palladino Rita Emili Mariagrazia De Lisa Donatella Sarti Vincenzo Catalano Mauro Magnani Francesco Graziano Annamaria Ruzzo KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus Pembrolizumab Scientific Reports |
| title | KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus Pembrolizumab |
| title_full | KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus Pembrolizumab |
| title_fullStr | KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus Pembrolizumab |
| title_full_unstemmed | KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus Pembrolizumab |
| title_short | KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus Pembrolizumab |
| title_sort | kras4a and kras4b in liquid biopsy of metastatic lung adenocarcinoma patients treated with pembrolizumab or chemotherapy plus pembrolizumab |
| url | https://doi.org/10.1038/s41598-023-48304-0 |
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