Genetic Markers Predict Poor NSCLC Prognosis

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(ChemotherapyAdvisor) – High levels of tropomyosin-related kinase B (TrkB) and brain-derived neurotrophic factor (BDNF) expression predict vascular invasion by non-small cell lung cancer (NSCLC) tumors and poor patient prognosis, according to a new study in Japan, published in Lung Cancer.

“(C)o-expression of TrkB and BDNF conferred poorer prognosis compared with overexpression of either protein alone,” noted lead author Kyoko Okamura, MD, Research Institute for Diseases of the Chest, Kyushu University, Japan, and coauthors.

TrkB, a receptor tyrosine kinase, binds to neurotrophic growth-factor proteins, including BDNF. Previous research has shown that elevated TrkB and BDNF expression is associated with “aggressive malignant behavior” in tumor cells and poor prognosis for patients with several types of cancer, including breast, pancreatic, colon, gastric and hepatocellular cancer, Wilms' tumor, and neuroblastoma, Okamura and colleagues wrote.

“TrkB is thought to be a key regulator of oncogenesis and tumor progression,” Okamura and colleagues wrote.

To determine if TrkB and its BDNF ligand similarly affect tumors and patient prognosis in NSCLC, the authors immunohistochemically assessed TrkB and BDNF expression in surgically-resected NSCLC tumors.

Vascular invasion was significantly associated with expression of both TrkB (P = 0.010) and BDNF (P = 0.015), the authors report. Nonlinear Spearman's rank correlation analysis found a strong correlation between TrkB and BDNF expression in lung tumors (r = 0.58, P < 0.0001).

“TrkB-positive tumors had significantly worse disease-free survival (P = 0.0094) and overall survival (OS; P = 0.0019) than TrkB-negative tumors, and TrkB expression was an independent prognostic factor for disease-free survival (HR = 3.735, 95% CI, 1.56–11.068, P = 0.002),” the team wrote.

“Our results might provide a novel way to explore targeted therapy in lung cancer patients,” the authors wrote.

This and previous research suggests that Trk inhibitors are candidate therapies for TrkB-positive NSCLC, the authors reported. Clinical studies are needed to determine the effects of Trk inhibitors in these patients, they wrote.


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