A novel tailored immune gene pairs signature for overall survival prediction in lower-grade gliomas

Pan, Xuyan; Wang, Zhanhui; Liu, Fang; Zou, Feihui; Xie, Qijun; Guo, Yi-Zhuo; Shen, Liang

doi:10.1016/j.tranon.2021.101109

Cited by 3 publications

(2 citation statements)

References 49 publications

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“…One possibility is that NRG3 is able to suppress or otherwise modulate NRG1-mediated activation of ERBB4-positive cells. In our TCGA data analysis, NRG3 showed reduced expression in grade 4 tumors, and low expression was associated with worse OS in IDHmut astrocytomas both in univariate and multivariate analysis, consistent with previous reports on its prognostic role in diffuse glioma in general [ 57 – 59 ]. Our results clearly linked the gene to IDHmut astrocytoma progression to grade 4.…”

Section: Discussionsupporting

confidence: 91%

Genomic characterization of IDH-mutant astrocytoma progression to grade 4 in the treatment setting

Rautajoki,

Jaatinen,

Hartewig

et al. 2023

acta neuropathol commun

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As the progression of low-grade diffuse astrocytomas into grade 4 tumors significantly impacts patient prognosis, a better understanding of this process is of paramount importance for improved patient care. In this project, we analyzed matched IDH-mutant astrocytomas before and after progression to grade 4 from six patients (discovery cohort) with genome-wide sequencing, 21 additional patients with targeted sequencing, and 33 patients from Glioma Longitudinal AnalySiS cohort for validation. The Cancer Genome Atlas data from 595 diffuse gliomas provided supportive information. All patients in our discovery cohort received radiation, all but one underwent chemotherapy, and no patient received temozolomide (TMZ) before progression to grade 4 disease. One case in the discovery cohort exhibited a hypermutation signature associated with the inactivation of the MSH2 and DNMT3A genes. In other patients, the number of chromosomal rearrangements and deletions increased in grade 4 tumors. The cell cycle checkpoint gene CDKN2A, or less frequently RB1, was most commonly inactivated after receiving both chemo- and radiotherapy when compared to other treatment groups. Concomitant activating PDGFRA/MET alterations were detected in tumors that acquired a homozygous CDKN2A deletion. NRG3 gene was significantly downregulated and recurrently altered in progressed tumors. Its decreased expression was associated with poorer overall survival in both univariate and multivariate analysis. We also detected progression-related alterations in RAD51B and other DNA repair pathway genes associated with the promotion of error-prone DNA repair, potentially facilitating tumor progression. In our retrospective analysis of patient treatment and survival timelines (n = 75), the combination of postoperative radiation and chemotherapy (mainly TMZ) outperformed radiation, especially in the grade 3 tumor cohort, in which it was typically given after primary surgery. Our results provide further insight into the contribution of treatment and genetic alterations in cell cycle, growth factor signaling, and DNA repair-related genes to tumor evolution and progression.

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Section: Discussionsupporting

confidence: 91%

Genomic characterization of IDH-mutant astrocytoma progression to grade 4 in the treatment setting

Rautajoki,

Jaatinen,

Hartewig

et al. 2023

acta neuropathol commun

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“…Studies already show evidence about gene signatures, such as autophagy genes related, strongly associated with six immune cell infiltrates (macrophages M0 and M1, Neutrophils, T cells CD8, T cells follicular helper, T cells reg) in LGG (Quan et al, 2021). Additionally, other gene signatures, such as immune-related genes, demonstrate positive and negative correlations with several immune cell infiltrates in LGG (macrophages, dendritic cells, B cells, and CD4 T cells) (Pan et al, 2021). In the same way, our study showed positive and negative correlations with immune infiltrates in LGG, with monocyte, NK, and B cells, T cell CD4+, macrophage (M1 and M2), and myeloid dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

A Sexual Bias in mitochondrial protein-coding gene expression across different tissues and the prognostic value in multiple cancers

Silva

Ferreira

Medina‐Acosta

2022

Preprint

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Mitochondria in mammalian cells provide ATP through oxidative phosphorylation. The overproduction of reactive oxygen species (ROS) in mitochondrial cells promotes cancer by modifying gene expression or function. Mating introduces competing mitochondrial (mtDNA) and nuclear DNA (nDNA) gene products, leading to biological differences between males and females for diseases and disorders such as cancer. There is a significant sex bias in aging-related conditions. We aimed to investigate whether sex and age affect mitochondrial protein-coding gene expression in cancer and, if so, to determine the prognosis value in survival outcomes, stemness, and immune cell infiltrates. We compared normal versus primary tumor transcriptomes (bulk RNA-Seq) from The Cancer Genome Atlas (TCGA), and the Genotype-Tissue Expression (GTEx) projects to test these hypotheses. Correlations between gene expression, survival, protective or risk factor, stemness, and immune cell infiltrate were performed in RStudio using UCSC Xena Shiny. Eleven mitochondrial protein-coding genes were altered in brain cancer (MT-ND2, MT-ND1, MT-ATP8, MT-ATP6, MT-CO2, MT-CYB, MT-CO3, MT-ND4L, MT-ND4, MT-ND3, MT-CO1). MT-ND5 and MT-ND6 are disproportionately expressed in female brain tissues. Mitochondrial global polymorphic expression sites of variation were more significant in the 50-59 and 60-79-year-old age groups than in the 20-49-year-old age groups. Pan-cancer survival analysis revealed a 4-component gene signature (MT-CO1, MT-CO2, MT-ND5, and MT-ND6) downregulated in low-grade glioma (LGG). This gene signature increased LGG overall survival, disease-specific survival, and progression-free interval without sex-specific association. However, the correlation with disease-free interval survival was female-specific. The 4-component gene signature was protective in LGG but risky in thymoma cancer and uterine corpus endometrial carcinoma. In LGG, the 4-component gene signature positively correlated with immune monocyte, NK, and B cell infiltrates and negatively correlated with T cell CD4+ Th2, macrophage M1 and M2, myeloid dendritic cell, and neutrophil. We identified a 13-component mitochondrial protein-coding gene signature associated with stemness in kidney chromophobe. A sex-biased effect was observed in mitochondrial protein-coding for brain tissues, with a female bias. However, an aging effect with higher polymorphic site expression was observed in male tissues. We conclude that the differentially expressed mitochondrial protein-coding genes provide new insights into carcinogenesis, helping to identify new prognostic markers. The overexpression of the 4-component gene signature is associated with a better prognosis in LGG, with positive and negative correlations with immune cell infiltrates.

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Integrated GMPS and RAMP3 as a signature to predict prognosis and immune heterogeneity in hepatocellular carcinoma

Chen,

Zeng,

et al. 2025

Gene

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A novel tailored immune gene pairs signature for overall survival prediction in lower-grade gliomas

Cited by 3 publications

References 49 publications

Genomic characterization of IDH-mutant astrocytoma progression to grade 4 in the treatment setting

Genomic characterization of IDH-mutant astrocytoma progression to grade 4 in the treatment setting

A Sexual Bias in mitochondrial protein-coding gene expression across different tissues and the prognostic value in multiple cancers

Integrated GMPS and RAMP3 as a signature to predict prognosis and immune heterogeneity in hepatocellular carcinoma

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