Codon-specific KRAS mutations predict survival in advanced pancreatic cancer Article Swipe
Alice Boilève
,
Adrien Rousseau
,
Marc Hilmi
,
A. Tarabay
,
Jacques R.R. Mathieu
,
Jérôme Cartry
,
Sabrina Bedja
,
N. Goudarzi
,
Claudio Nicotra
,
Maud Ngo‐Camus
,
V. Boige
,
Marine Valéry
,
T. Pudlarz
,
Mohamed‐Amine Bani
,
Peggy Dartigues
,
Lambros Tselikas
,
Antoîne Italiano
,
Simona Cosconea
,
Maximiliano Gelli
,
Elena Fernandez-De-Sevilla
,
David Malka
,
Maxime Annereau
,
Fanny Jaulin
,
Cristina Smolenschi
,
Antoine Hollebecque
,
Michel Ducreux
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.esmogo.2023.100030
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.esmogo.2023.100030
Background: How distinct KRAS alterations in pancreatic adenocarcinoma (PDAC) influence tumor initiation and outcomes remains unclear. Moreover, KRAS is now partly targetable with novel specific inhibitors targeting KRASG12 (G12C or G12D), but specific outcomes of these subgroups of patients is poorly described. In this study, we compared clinical/genomic characteristics and outcomes of PDAC depending on codon-specific KRAS mutant (G12 versus others), as well as gene expression profiles and in vitro drug sensibility using organoids. Patients and methods: All metastatic patients with PDAC and available molecular profile from 2015 to 2022 were eligible, and patients with KRAS mutation were included. Transcriptomic data from 69 KRAS-mutated tumors were also analyzed. Results: Overall, 263 patients were included—239 KRASG12 (91%) and 24 (9%) KRASother. There was no difference between KRASG12 and KRASother regarding clinicopathological characteristics and potentially actionable alterations, except for BRAF that was found in 13% of KRASother (P = 0.01). G protein subunit alpha S (GNAS) was found more altered in KRASother tumors (P = 0.002) suggesting potential intraductal papillary mucinous neoplasm precursors. The median overall survival from metastatic diagnosis was 16.7 months [95% confidence interval (CI) 14.3-18.3 months] in KRASG12 and 24.9 months (95% CI 17.4-43.4 months) in KRASother [hazard ratio (ref: KRASG12) = 0.56 (0.34-0.94), P = 0.04 adjusted]. The first-line treatment response was not different between groups (overall response rate and progression-free survival), as confirmed with a similar organoid in vitro sensibility. Transcriptomic analyses showed a significant and exclusive up-regulation of immune pathways in KRASG12 tumors. Conclusions: Codon-specific KRAS mutations are not equal and we report that KRASG12 patients have a worst prognosis than KRASother patients in PDAC. These results warrant to be confirmed in larger-scale studies.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.esmogo.2023.100030
- http://www.esmogastro.org/article/S2949819823000456/pdf
- OA Status
- diamond
- Cited By
- 5
- References
- 36
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391160742
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4391160742Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1016/j.esmogo.2023.100030Digital Object Identifier
- Title
-
Codon-specific KRAS mutations predict survival in advanced pancreatic cancerWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-01-24Full publication date if available
- Authors
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Alice Boilève, Adrien Rousseau, Marc Hilmi, A. Tarabay, Jacques R.R. Mathieu, Jérôme Cartry, Sabrina Bedja, N. Goudarzi, Claudio Nicotra, Maud Ngo‐Camus, V. Boige, Marine Valéry, T. Pudlarz, Mohamed‐Amine Bani, Peggy Dartigues, Lambros Tselikas, Antoîne Italiano, Simona Cosconea, Maximiliano Gelli, Elena Fernandez-De-Sevilla, David Malka, Maxime Annereau, Fanny Jaulin, Cristina Smolenschi, Antoine Hollebecque, Michel DucreuxList of authors in order
- Landing page
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https://doi.org/10.1016/j.esmogo.2023.100030Publisher landing page
- PDF URL
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https://www.esmogastro.org/article/S2949819823000456/pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
diamondOpen access status per OpenAlex
- OA URL
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https://www.esmogastro.org/article/S2949819823000456/pdfDirect OA link when available
- Concepts
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KRAS, Pancreatic cancer, Oncology, Cancer research, Biology, Mutation, Genetics, Internal medicine, Computational biology, Medicine, Cancer, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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5Total citation count in OpenAlex
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2025: 4, 2024: 1Per-year citation counts (last 5 years)
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36Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| citation_normalized_percentile.value | 0.86806108 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |