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Favorable outcome of patients with lung adenocarcinoma harboring POLE mutations
and expressing high PD-L1
#MMPMID29650000
Liu L
; Ruiz J
; O'Neill SS
; Grant SC
; Petty WJ
; Yang M
; Chen K
; Topaloglu U
; Pasche B
; Zhang W
Mol Cancer
2018[Apr]; 17
(1
): 81
PMID29650000
show ga
Mutations in polymerase ? (POLE) confer favorable prognosis and outcomes in
various cancer types, but their role in non-small cell lung cancer (NSCLC) is
unknown. Utilizing the data of 513 patients with adenocarcinoma (LUAD) and 497
patients with squamous cell carcinoma (LUSC) from The Cancer Genome Atlas (TCGA)
cohort, we tested the prognostic value of POLE mutations and programmed cell
death ligand 1 (PD-L1) expression in the two main subtypes of NSCLC. POLE
mutation is a favorable biomarker for the improved overall survival (OS) of the
LUSC patients (P?= 0.033, 28 mutant vs. 469 wildtype patients), but not that of
the LUAD patients (P?= 0.12, 31 mutant vs. 482 wildtype patients). POLE-mutant
LUAD patients with high expression of PD-L1 (Mut-High, n =?6) exhibited improved
OS (P?= 0.024) when compared to POLE-mutant patients with low PD-L1 expression
(Mut-Low, n =?24) and other patients without POLE mutation (n =?476). This
benefit was not due to the high content of the tumor infiltrating lymphocytes.
Instead, the antitumor immune response was activated in Mut-High patients so that
these patients were likely responding more effectively to immuno-oncology (IO)
treatments; whereas genes involved with metabolic pathways were enriched in
Mut-Low group, which may cause the decreased OS of these patients. Our study
sheds light on the molecular basis of NSCLC and adds to our understanding of
responses to chemotherapy and IO therapy.
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