Abstract PO005: The overexpression of Immune oncology-related genes NFSF14, LY96, SLC11A1 and CTSL are associated with short survival in glioblastoma
Authors: Moreno Daniel , Sussuchi Luciane , Leal Letícia , Sorroche Bruna , Santana Iara , Matsushita Marcus , Bhat Krishna , Lawlew Sean , Reis Rui 
Published: February 2021

Background: Glioblastomas (GB) are the most common primary malignant brain tumors in adults. The standard therapy consists of surgery, radiotherapy and concomitant and adjuvant administration of temozolomide (TMZ). GB is a heterogeneous disease and despite extensive efforts for improving treatment strategies in the last decades, few advances have been reached in patients’ overall survival (OS), which remains nearly 15 months. Recently, many researches have been focusing on the tumor microenvironment which is particularly immunosuppressed in GB and more studies are necessary to investigate the immunological factors involved in tumor progression for the development of new therapeutic approaches.

Objectives: The present study aimed to evaluate the expression profile of 730 genes associated with immune-oncology using NanoString in 37 primary GB samples from patients treated with TMZ and investigate the relationships with patient’s survival and response to TMZ.

Methods: In this retrospective study, GB patients from Barretos Cancer Hospital (BCH), Brazil, were divided into short term survivals (STS), OS &lt; 12 months (n=26) and Long term survivals (LTS), OS &gt; 3 years (n=11). The OS was calculated from the date of diagnosis to death or last follow up. The RNA was extracted from FFPE samples (first surgery), using the RNAeasy mini kit (Qiagen) and quantified using Qubit HS assay (ThermoFisher). The evaluation of mRNA levels was performed using the Pan-Cancer Immunoprofiling panel, which contains 770 targets with 730 immuno-oncology related and 40 housekeeping genes. The nSolver software and the Advanced analysis package (NanoString Technologies) was used for data analysis. The TCGA data banks (cBioPortal – RNAseq TCGA 2013/2018 and Betastasis – microarrays, Affymetrix Human Exon 1.0 ST/ HT HG U133A) were assessed to confirm our findings.

Results: The NanoString analyses revealed that 24 immuno-oncology related genes were significantly upregulated in GB STS (p&lt;0.001). The in silico analysis of RNAseq and microarrays TCGA data, confirmed that the overexpression of 4 genes, including TNFSF14, LY96, SLC11A1, and CTSL, were found to be associated with poor survival in at least 2 data banks, corroborating with the present survey.

Conclusion: In the present study we found that immune-oncology related genes as NFSF14, LY96, SLC11A1, and CTSL, are overexpressed in GB. These genes are possible biomarkers of TMZ response in GB. Future functional studies should be conducted to evaluate the potential of these targets for immunotherapy.

Citation Format: Daniel Moreno, Luciane Sussuchi, Letícia Leal, Bruna Sorroche, Iara Santana, Marcus Matsushita, Krishna Bhat, Sean Lawlew, Rui Reis. The overexpression of Immune oncology-related genes NFSF14, LY96, SLC11A1 and CTSL are associated with short survival in glioblastoma [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO005.