A SEMA3 Signaling Pathway-Based Multi-Biomarker for Prediction of Glioma Patient Survival.

Indre Valiulyte,Giedrius Steponaitis,Arunas Kazlauskas,Deimante Kardonaite,Arimantas Tamasauskas

doi:10.3390/ijms21197396

Indre Valiulyte, Giedrius Steponaitis + Show 3 more

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https://doi.org/10.3390/ijms21197396

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Abstract

Glioma is a lethal central nervous system tumor with poor patient survival prognosis. Because of the molecular heterogeneity, it is a challenge to precisely determine the type of the tumor and to choose the most effective treatment. Therefore, novel biomarkers are essential to improve the diagnosis and prognosis of glioma tumors. Class 3 semaphorin proteins (SEMA3) play an important role in tumor biology. SEMA3 transduce their signals by using neuropilin and plexin receptors, which functionally interact with the vascular endothelial growth factor-mediated signaling pathways. Therefore, the aim of this study was to explore the potential of SEMA3 signaling molecules for prognosis of glioma patient survival. The quantitative real-time PCR method was used to evaluate mRNA expression of SEMA3(A-G), neuropilins (NRP1 and NRP2), plexins (PLXNA2 and PLXND1), cadherins (CDH1 and CDH2), integrins (ITGB1, ITGB3, ITGA5, and ITGAV), VEGFA and KDR genes in 59 II-IV grade glioma tissues. Seven genes significantly associated with patient overall survival were used for multi-biomarker construction, which showed 64%, 75%, and 68% of accuracy of predicting the survival of 1-, 2-, and 3-year glioma patients, respectively. The results suggest that the seven-gene signature could serve as a novel multi-biomarker for more accurate prognosis of a glioma patient’s outcome.

Highlights

Gliomas are the most common and lethal central nervous system (CNS) tumors with unfavorable patient survival prognosis
SEMA3 transduce their signals by using neuropilin and plexin receptors in complex with integrins [19,20], cadherins [21,22], and vascular endothelial growth factor receptors (VEGFR) [23,24], showing the ability of SEMA3 proteins to activate and regulate a variety of different signaling pathways [15,19]
The expression of SEMA3(A-G), NRP1, NRP2, PLXNA2, PLXND1, CDH1, CDH2, ITGB1, ITGB3, ITGA5, ITGAV, KDR, and VEGFA genes at mRNA level were compared between astrocytoma and healthy human brain samples

Summary

Introduction

Gliomas are the most common and lethal central nervous system (CNS) tumors with unfavorable patient survival prognosis. The incidence rate of glioma patients is about 7.3 per 100,000 persons a year, which is higher in men than in women (8.7 cases and 5.9 cases, respectively). Diffuse glioma is the most common type, according to WHO classification 2016, graded as WHO grade II (diffuse), WHO grade III (anaplastic) and WHO grade IV (glioblastoma) [2,3]. It is noteworthy that some of the tumor cells may be resistant to therapy, and drugs used for treatments can lead to side effects [5]. Despite the complex treatment (surgery, chemotherapy, and radiation therapy), the survival time of patients is generally short (approximately 14 months after initial diagnosis) [6]

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