Exploration of the Radiosensitivity-related Prognostic Risk Signature in Patients with Glioma: Evidence from Microarray Data

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2023 Sep 12

PMID 37700319

Authors

Xiaonan Zhang

QianNan Ren

Zhiyong Li

Xiaolin Xia

Wan Zhang

Yue Qin

Dehua Wu

Chen Ren

Affiliations

Soon will be listed here.

Abstract

Background: Gene expression signatures can be used as prognostic biomarkers in various types of cancers. We aim to develop a gene signature for predicting the response to radiotherapy in glioma patients.

Methods: Radio-sensitive and radio-resistant glioma cell lines (M059J and M059K) were subjected to microarray analysis to screen for differentially expressed mRNAs. Additionally, we obtained 169 glioblastomas (GBM) samples and 5 normal samples from The Cancer Genome Atlas (TCGA) database, as well as 80 GBM samples and 4 normal samples from the GSE7696 set. The "DESeq2" R package was employed to identify differentially expressed genes (DEGs) between the normal brain samples and GBM samples. Combining the prognostic-related molecules identified from the TCGA, we developed a radiosensitivity-related prognostic risk signature (RRPRS) in the training set, which includes 152 patients with glioblastoma. Subsequently, we validated the reliability of the RRPRS in a validation set containing 616 patients with glioma from the TCGA database, as well as an internal validation set consisting of 31 glioblastoma patients from the Nanfang Hospital, Southern Medical University.

Results: Based on the microarray and LASSO COX regression analysis, we developed a nine-gene radiosensitivity-related prognostic risk signature. Patients with glioma were divided into high- or low-risk groups based on the median risk score. The Kaplan-Meier survival analysis showed that the progression-free survival (PFS) of the high-risk group was significantly shorter. The signature accurately predicted PFS as assessed by time-dependent receiver operating characteristic curve (ROC) analyses. Stratified analysis demonstrated that the signature is specific to predict the outcome of patients who were treated using radiotherapy. Univariate and multivariate Cox regression analysis revealed that the predictor was an independent predictor for the prognosis of patients with glioma. The prognostic nomograms accompanied by calibration curves displayed the 1-, 2-, and 3-year PFS and OS in patients with glioma.

Conclusion: Our study established a new nine-gene radiosensitivity-related prognostic risk signature that can predict the prognosis of patients with glioma who received radiotherapy. The nomogram showed great potential to predict the prognosis of patients with glioma treated using radiotherapy.

Citing Articles

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PMID: 39675252 PMC: 11713735. DOI: 10.1016/j.tranon.2024.102243.

Clinical Biomarkers of Tumour Radiosensitivity and Predicting Benefit from Radiotherapy: A Systematic Review.

Bleaney C, Abdelaal H, Reardon M, Anandadas C, Hoskin P, Choudhury A Cancers (Basel). 2024; 16(10).

PMID: 38792019 PMC: 11119069. DOI: 10.3390/cancers16101942.

References

Gritsch S, Batchelor T, Gonzalez Castro L . Diagnostic, therapeutic, and prognostic implications of the 2021 World Health Organization classification of tumors of the central nervous system. Cancer. 2021; 128(1):47-58. DOI: 10.1002/cncr.33918. View

Miller K, Ostrom Q, Kruchko C, Patil N, Tihan T, Cioffi G . Brain and other central nervous system tumor statistics, 2021. CA Cancer J Clin. 2021; 71(5):381-406. DOI: 10.3322/caac.21693. View

Chen F, Wendl M, Wyczalkowski M, Bailey M, Li Y, Ding L . Moving pan-cancer studies from basic research toward the clinic. Nat Cancer. 2022; 2(9):879-890. DOI: 10.1038/s43018-021-00250-4. View

Stupp R, Hegi M, Mason W, van den Bent M, Taphoorn M, Janzer R . Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009; 10(5):459-66. DOI: 10.1016/S1470-2045(09)70025-7. View

Stupp R, Mason W, van den Bent M, Weller M, Fisher B, Taphoorn M . Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10):987-96. DOI: 10.1056/NEJMoa043330. View

Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B . Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017; 318(23):2306-2316. PMC: 5820703. DOI: 10.1001/jama.2017.18718. View

Gebhardt B, Dobelbower M, Ennis W, Bag A, Markert J, Fiveash J . Patterns of failure for glioblastoma multiforme following limited-margin radiation and concurrent temozolomide. Radiat Oncol. 2014; 9:130. PMC: 4055938. DOI: 10.1186/1748-717X-9-130. View

Minniti G, Amelio D, Amichetti M, Salvati M, Muni R, Bozzao A . Patterns of failure and comparison of different target volume delineations in patients with glioblastoma treated with conformal radiotherapy plus concomitant and adjuvant temozolomide. Radiother Oncol. 2010; 97(3):377-81. DOI: 10.1016/j.radonc.2010.08.020. View

Ou A, Yung W, Majd N . Molecular Mechanisms of Treatment Resistance in Glioblastoma. Int J Mol Sci. 2021; 22(1). PMC: 7794986. DOI: 10.3390/ijms22010351. View

10.

Ali M, Oliva C, Noman A, Allen B, Goswami P, Zakharia Y . Radioresistance in Glioblastoma and the Development of Radiosensitizers. Cancers (Basel). 2020; 12(9). PMC: 7564557. DOI: 10.3390/cancers12092511. View

11.

Ruff M, Uhm J, Benarroch E . Neuro-oncology: Implications of the molecular era. Neurology. 2019; 92(12):568-574. DOI: 10.1212/WNL.0000000000007126. View

12.

Louis D, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee W . The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016; 131(6):803-20. DOI: 10.1007/s00401-016-1545-1. View

13.

Wong Q, Li K, Wang W, Malta T, Noushmehr H, Grabovska Y . Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas. Mod Pathol. 2021; 34(7):1245-1260. DOI: 10.1038/s41379-021-00778-x. View

14.

Zhang J, Song W, Chen Z, Wei J, Liao Y, Lei J . Prognostic and predictive value of a microRNA signature in stage II colon cancer: a microRNA expression analysis. Lancet Oncol. 2013; 14(13):1295-306. DOI: 10.1016/S1470-2045(13)70491-1. View

15.

Chen Y, Li Z, Zhou G, Sun Y . An Immune-Related Gene Prognostic Index for Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2020; 27(1):330-341. DOI: 10.1158/1078-0432.CCR-20-2166. View

16.

Bai X, Wu D, Ma S, Wang J, Tang X, Kang S . Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study. J Immunother Cancer. 2020; 8(1). PMC: 7328897. DOI: 10.1136/jitc-2019-000381. View

17.

Lin W, Huang Z, Xu Y, Chen X, Chen T, Ye Y . A three-lncRNA signature predicts clinical outcomes in low-grade glioma patients after radiotherapy. Aging (Albany NY). 2020; 12(10):9188-9204. PMC: 7288909. DOI: 10.18632/aging.103189. View

18.

Zhang J, Hou R, Pan Y, Gao Y, Yang Y, Tian W . A five-microRNA signature for individualized prognosis evaluation and radiotherapy guidance in patients with diffuse lower-grade glioma. J Cell Mol Med. 2020; 24(13):7504-7514. PMC: 7339211. DOI: 10.1111/jcmm.15377. View

19.

Yan D, Zhao Q, Du Z, Li H, Geng R, Yang W . Development and validation of an immune-related gene signature for predicting the radiosensitivity of lower-grade gliomas. Sci Rep. 2022; 12(1):6698. PMC: 9035187. DOI: 10.1038/s41598-022-10601-5. View

20.

Barron G, Day 3rd R, Dobler K, Mirzayans R . Isolation of two cell lines from a human malignant glioma specimen differing in sensitivity to radiation and chemotherapeutic drugs. Radiat Res. 1993; 134(3):349-54. View