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. 2017 Oct:112:62-68.
doi: 10.1016/j.lungcan.2017.08.002. Epub 2017 Aug 7.

LKB1/STK11 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value

Francesco Facchinetti  1 , Maria Virginia Bluthgen  2 , Gabrielle Tergemina-Clain  3 , Laura Faivre  4 , Jean-Pierre Pignon  5 , David Planchard  6 , Jordi Remon  7 , Jean-Charles Soria  8 , Ludovic Lacroix  9 , Benjamin Besse  10
Affiliations

LKB1/STK11 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value

Francesco Facchinetti et al. Lung Cancer. 2017 Oct.

Abstract

Background: LKB1/STK11 (STK11) is among the most inactivated tumor-suppressor genes in non-small cell lung cancer (NSCLC). While evidence concerning the biologic role of STK11 is accumulating, its prognostic significance in advanced NSCLC has not been envisaged yet.

Materials and methods: This retrospective analysis included consecutive NSCLC patients with available STK11 information who underwent a platinum-based chemotherapy. STK11 mutational status was correlated to clinico-pathological and mutational features. Kaplan-Meier and Cox models were used for survival curves and multivariate analyses, respectively.

Results: Among the 302 patients included, 267 (89%) were diagnosed with stage IIIB/IV NSCLC and 25 (8%) harbored a STK11 mutation (STK11mut). No statistical differences were observed between STK11 status and clinico-pathological variables. We detected a significant correlation between STK11 and KRAS status (p=0.008); among the 25 STK11mut patients, 13 (52%) harbored a concomitant KRAS mutation. Overall survival (OS) was shorter for STK11mut (median OS=10.4months) compared to wild-type patients (STK11wt; median OS=17.3months) in univariate analysis (p=0.085). STK11 status did not impact upon OS in multivariate analysis (p=0.45) and non-significant results were observed for progression-free survival. The co-occurrence of KRAS and STK11 mutations suggest a trend toward detrimental effect in OS (p=0.12).

Conclusions: In our cohort enriched for advanced NSCLC patients who received platinum-based chemotherapy, STK11 mutations were not specifically associated with clinico-pathological features and they did not impact upon survival. We confirm the positive correlation between STK11 and KRAS mutations. The co-occurrence of KRAS and STK11 mutations could label a more aggressive molecular subtype of NSCLC.

Keywords: Advanced stage; KRAS; LKB1/STK11; Mutations; Non-small cell lung cancer; Prognostic biomarker.

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