Dataset Information

AXL-GAS6 expression can predict for adverse prognosis in non-small cell lung cancer with brain metastases.

ABSTRACT:

Purpose

Patients with non-small cell lung cancer (NSCLC) brain metastases (BM) have poor clinical outcomes. We sought to determine if AXL-GAS6 expression can be used as independent prognostic biomarkers for NSCLC BM.

Methods

We retrospectively studied the medical records of 98 patients diagnosed with advanced metastatic NSCLC from December 2000 to June 2014. Out of a total of 98 patients with NSCLC metastases, 66 patients were identified to have brain metastases. The expressions of AXL and GAS6 were assessed by standard immunohistochemistry and correlated with clinicopathological factors and overall survival (OS) outcomes.

Results

The expression of AXL was positively associated with GAS6 expression (P?ConclusionsAXL-GAS6 co-expression represents a potential independent prognostic biomarker for survival outcome in NSCLC BM patients.

SUBMITTER: Wu X

PROVIDER: S-EPMC5599460 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

AXL-GAS6 expression can predict for adverse prognosis in non-small cell lung cancer with brain metastases.

Wu Xiaoliang X Ma Wenjuan W Zhou Qianghua Q Yan Haijuan H Lim Zuan-Fu ZF Huang Mayan M Deng Chuangzhong C Yu Xingsu X Su Huifang H Komo Satoshi S Yang Haixia H Zhang Xinke X Wen Sijin S Zhang Zhenfeng Z Ma Patrick C PC

Journal of cancer research and clinical oncology 20170527 10

<h4>Purpose</h4>Patients with non-small cell lung cancer (NSCLC) brain metastases (BM) have poor clinical outcomes. We sought to determine if AXL-GAS6 expression can be used as independent prognostic biomarkers for NSCLC BM.<h4>Methods</h4>We retrospectively studied the medical records of 98 patients diagnosed with advanced metastatic NSCLC from December 2000 to June 2014. Out of a total of 98 patients with NSCLC metastases, 66 patients were identified to have brain metastases. The expressions o ...[more]

PMID: 28551766

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Project description:BackgroundBrain metastases (BM) are a frequent complication of advanced cancer and are characterized by a variety of neurological symptoms. Although the presence of neurological symptoms is included in the response assessment in patients with primary brain tumors, to the authors' knowledge little is known regarding the prognostic impact of neurological symptoms in patients with BM.MethodsPatients with newly diagnosed BM from non-small cell lung cancer were identified from the Vienna Brain Metastasis Registry and were evaluated according to the incidence, distribution, and prognostic impact of neurological symptoms at the time of diagnosis of BM.ResultsA total of 1608 patients (57.3% male and 42.7% female; median age, 62 years) were available for further analyses. Neurological symptoms including focal deficits (985 patients; 61.3%), signs of increased intracranial pressure (483 patients; 30.0%), epileptic seizures (224 patients; 13.9%), and neuropsychological symptoms (233 patients; 14.5%) were documented in 1186 of the 1608 patients (73.8%). Patients with asymptomatic BM presented with a longer median overall survival after the diagnosis of BM compared with patients with symptomatic BM (11 months vs 7 months; P < .001). In multivariate analysis with a diagnosis-specific graded prognostic assessment (hazard ratio, 1.41; 95% CI, 1.33-1.50 [P < .001]), the presence of neurological symptoms (hazard ratio, 1.39; 95% CI, 1.23-1.57 [P < .001]) was found to be independently associated with survival prognosis from the time of diagnosis of BM.ConclusionsNeurological symptoms at the time of BM diagnosis demonstrated a strong and independent association with survival prognosis. The results of the current study have highlighted the need for the integration of the presence of neurological symptoms into the prognostic assessment of patients with BM from non-small cell lung cancer.Lay summaryNeurological symptom evaluation is included regularly in the assessment of patients with primary brain tumors. However, to the authors' knowledge, little is known regarding the prognostic impact in patients with newly diagnosed brain metastases (BM). The current study has provided a detailed clinical characterization of the incidence, distribution, and prognostic impact of neurological symptoms in a large, real-life cohort of patients with BM from non-small cell lung cancer. In this cohort, neurological symptoms at the time of diagnosis of BM demonstrated a strong, independent prognostic impact on the survival prognosis. The results of the current study have highlighted the need for the integration of neurological symptom burden into the prognostic assessment of patients with BM from non-small cell lung cancer.

Project description:Brain metastases (BM) have been closely associated with increased morbidity and poor survival outcomes in patients with non‑small cell lung cancer (NSCLC). Excluding risk factors in histological subtypes, genomic alterations, including epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangements have been also regarded as greater risk factors for BM in the aspect of molecular subtypes. In the present study, 69 tumor tissues and 51 peripheral blood samples from patients with NSCLC were analyzed using a hybridization capture‑based next‑generation sequencing (NGS) panel, including 95 known cancer genes. Among the 90 patients with stage IV NSCLC, 26 cases suffered from BM and 64 cases did not. In total, 174 somatic mutations in 35 mutated genes were identified, and 12 of these genes were concurrently present in the BM group and the non‑BM group. Importantly, five mutated genes including ALK, cytidine deaminase (CDA), SMAD family member 4 (SMAD4), superoxide dismutase 2 (SOD2) and Von Hippel‑Lindau tumor suppressor (VHL) genes were uniquely detected in the BM group, and they were enriched in the Hippo signaling pathway, pyrimidine metabolism and pantothenate and co‑enzyme A (CoA) biosynthesis, as demonstrated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RNA polymerase II transcription regulator complex and promyelocytic leukemia nuclear body were the top functional categories according to the Gene Ontology enrichment analysis in the BM group and non‑BM group, respectively. Furthermore, 43.33% (13/30) of mutated genes were detected by both tumor tissue deoxyribonucleic acid (DNA) and plasma‑derived circulating tumor DNA (ctDNA) in the non‑BM group, while this percentage was only limited to 29.41% (5/17) in the BM group. To summarize, significant differences in somatic mutations, somatic interactions, key signaling pathways, functional biological information, and clinical actionability for the therapy of targeted agents were founded between the BM group and the non‑BM group, and ctDNA analysis may by applied as a more credible alternative for genomic profiling in patients with advanced NSCLC without BM, due to its higher consistency for genomic profiling between ctDNA analysis and tissue DNA analysis.

Dataset Information

AXL-GAS6 expression can predict for adverse prognosis in non-small cell lung cancer with brain metastases.

Purpose

Methods

Results

Publications

AXL-GAS6 expression can predict for adverse prognosis in non-small cell lung cancer with brain metastases.

Similar Datasets

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