Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients' survival

Daniel Antunes Moreno; Luciane Sussuchi da Silva; Isabella Gomes; Letícia Ferro Leal; Gustavo Noriz Berardinelli; Gisele Melo Gonçalves; Caio Augusto Pereira; Iara Viana Vidigal Santana; Marcus de Medeiros Matsushita; Krishna Bhat; Sean Lawler; Rui Manuel Reis

doi:10.1177/17588359221127678

Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients' survival

Ther Adv Med Oncol. 2022 Dec 21:14:17588359221127678. doi: 10.1177/17588359221127678. eCollection 2022.

Affiliations

¹ Molecular Oncology Research Center, Barretos, São Paulo, Brazil.
² Department of Molecular Diagnosis, Barretos, São Paulo, Brazil.
³ Department of Medical Oncology, Barretos, São Paulo, Brazil.
⁴ Pathology Department, BCH, Barretos, São Paulo, Brazil.
⁵ Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Harvard Medical School, Boston, MA, USA Brown University, Pathology and Laboratory Medicine, Providence, Rhode Island, USA.
⁷ Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, São Paulo CEP 14784 400, Brazil.
⁸ Department of Molecular Diagnosis, Barretos, São Paulo, Brazil ICVS/3B's PT Government Associate Laboratory, Braga/Guimarães, Portugal Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

Abstract

Introduction: Glioblastoma (GBM), isocitrate dehydrogenase (IDH) wild-type (IDH ^wt), and grade 4 astrocytomas, IDH mutant (IDH ^mut), are the most common and aggressive primary malignant brain tumors in adults. A better understanding of the tumor immune microenvironment may provide new biomarkers and therapeutic opportunities.

Objectives: We aimed to evaluate the expression profile of 730 immuno-oncology-related genes in patients with IDH ^wt GBM and IDH ^mut tumors and identify prognostic biomarkers and a gene signature associated with patient survival.

Methods: RNA was isolated from formalin-fixed, paraffin-embedded sections of 99 tumor specimens from patients treated with standard therapy. Gene expression profile was assessed using the Pan-Cancer Immune Profiling Panel (Nanostring Technologies, Inc., Seattle, WA, USA). Data analysis was performed using nSolverSoftware and validated in The Cancer Genome Atlas. In addition, we developed a prognostic signature using the cox regression algorithm (Least Absolute Shrinkage and Selection Operator).

Results: We found 88 upregulated genes, high immunological functions, and a high macrophage score in IDH ^wt GBM compared to IDH ^mut tumors. Regarding IDH ^wt GBM, we found 24 upregulated genes in short-term survivors (STS) and overexpression of CD274 (programmed death-ligand 1, PD-L1). Immune pathways, CD45, cytotoxic, and macrophage scores were upregulated in STS. Two different prognostic groups were found based on the 12-gene signature (CXCL14, PSEN2, TNFRSF13C, IL13RA1, MAP2K1, TNFSF14, THY1, CTSL, ITGAE, CHUK, CD207, and IFITM1).

Conclusion: The elevated expression of immune-oncology-related genes was associated with worse outcome in IDH ^wt GBM patients. Increased immune functions, CD45, cytotoxic cells, and macrophage scores were associated with a more aggressive phenotype and may provide promising possibilities for therapy. Moreover, a 12 gene-based signature could predict patients' prognosis.

Keywords: biomarkers; glioblastoma; immune-oncology; nCounter; prognosis.