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. 2023 Mar 30;15(7):2072.
doi: 10.3390/cancers15072072.

KRAS Mutations Are Associated with Shortened Survival in Patients with Epithelioid Malignant Pleural Mesothelioma

Margherita Vannucchi  1 , Veronica Pennati  2 , Clelia Mencaroni  2 , Chiara Defraia  1 , Ledi Bardhi  1 , Francesca Castiglione  2 , Cristiana Bellan  1 , Camilla Eva Comin  3
Affiliations

KRAS Mutations Are Associated with Shortened Survival in Patients with Epithelioid Malignant Pleural Mesothelioma

Margherita Vannucchi et al. Cancers (Basel). .

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural surface that includes three major histologic subtypes, epitheliod, sarcomatoid and biphasic. Epithelioid mesothelioma is usually associated with better prognosis. The genetic mechanisms driving MPM, the possible target mutations and the correlation with overall survival remain largely unsettled. We performed target exome sequencing in 29 cases of MPM aimed at identifying somatic mutations and, eventually, their correlation with phenotypic traits and prognostic significance. We found that KRAS mutations, occurring in 13.7% of cases, were associated with shortened median survival (7.6 versus 32.6 months in KRAS wild-type; p = 0.005), as it was the occurrence of any ≥3 mutations (7.6 versus 37.6 months; p = 0.049). Conversely, the presence of KDR single nucleotide polymorphism p.V297I (rs2305948) resulted in a favorable variable for survival (NR versus 23.4 months; p = 0.026). With the intrinsic limitations of a small number of cases and patient heterogeneity, results of this study contribute to the characterization of the mutation profile of MPM and the impact of selected somatic mutations, and possibly KDR polymorphism, on prognosis.

Keywords: KDR gene; KRAS mutation; MPM prognosis; epithelioid mesothelioma; pleural mesothelioma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
MPM with ≥3 mutations demonstrating a shorter overall survival.
Figure 2
Figure 2
Epithelioid MPM-KRAS mutated vs. epithelioid MPM-KRAS wild type.
Figure 3
Figure 3
SNP p.V297I of the KDR gene confers a significantly better prognosis in MPM patients.
See this image and copyright information in PMC

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