Sperm Autoantigenic Protein 17 Predicts the Prognosis and the Immunotherapy Response of Cancers: A Pan-Cancer Analysis

Tu, Zewei; Peng, Jie; Long, Xiaoyan; Li, Jingying; Wu, Lei; Huang, Kai; Zhu, Xingen

doi:10.3389/fimmu.2022.844736

Cited by 10 publications

(5 citation statements)

References 66 publications

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“…Single-cell data of GBMs were sourced from a previous study 16 and analyzed in the Tumor Immune Single-cell Hub (TISCH, http://tisch.comp-genomics.org/ 17 . The analysis procedure was conducted according to previous studies 18 . The data, identified by the serial number GSE89567 in the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/gds ), encompassed 6341 cells from 10 GBM patients, categorized into AC-like Malignant, Mono/Macro, OC-like Malignant, and Oligodendrocyte cell types.…”

Section: Methodsmentioning

confidence: 99%

ALKBH5 is a prognostic factor and promotes the angiogenesis of glioblastoma

Fan,

Yan,

et al. 2024

Sci Rep

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Despite numerous reports indicating the significant impact of RNA modification on malignant glioblastoma (GBM) cell behaviors such as proliferation, invasion and therapy efficacy, its specific involvement in glioblastoma (GBM) angiogenesis is remains unclear and is currently under investigation. In this study, we aimed to investigate the relevance between RNA modification regulators and GBM angiogenesis. Our study employed bioinformatic analyses, including Gene Set Enrichment Analysis (GSEA), differential expression analysis, and Kaplan–Meier survival analysis, to identify regulators of angiogenesis-associated RNA modification (RM). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to identify the enrichment of angiogenesis associated signatures in ALKBH5-high expression GBMs. We also utilized Western blot to verify the upregulation of ALKBH5 in clinical GBM samples. By a series of in vitro and in vivo assays, including plasmid transfection, wound healing, transwell invasion test, tube formation, RT-qPCR, ELISA assays and xenograft mice model, we validated the angiogenesis regulation ability of ALKBH5 in GBM. The N6-methyladenosine (m6A) modification “erase” ALKBH5 emerged as a candidate regulator associated with angiogenesis, demonstrating elevated expression and robust prognostic predictive ability in GBM patients. We also revealed enrichment of vasculature development biological process in GBMs with high ALKBH5 expression. Subsequently, we validated the elevated the expression of ALKBH5 in clinical GBM and paired adjacent tissues through western blot. Additionally, we knocked down the expression of ALKBH5 using sh-RNAs in U87 GBM cells to access the angiogenesis induction ability in U87 cells. In vitro experiments, Human Umbilical Vein Endothelial Cells (HUVECs) were used to perform wound healing, transwell migration and tube formation analysis, results indicated that ALKBH5 knock-down of U87 cells could decrease the pro-angiogenesis ability of U87 GBM cells. Further validation of our bioinformatic findings confirmed that ALKBH5 knockdown impaired VEGFA secretion in both in vitro and in vivo settings in U87 cells. These results comprehensively affirm the crucial role of ALKBH5 in regulating GBM-induced angiogenesis, both in vitro and in vivo. ALKBH5 not only emerges as a promising prognostic factor for GBM patients, but also plays a pivotal role in sustaining GBM progression by promoting angiogenesis.

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Section: Methodsmentioning

confidence: 99%

ALKBH5 is a prognostic factor and promotes the angiogenesis of glioblastoma

Fan,

Yan,

et al. 2024

Sci Rep

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“…The data visualization was performed through the R packages of “ggplot2”, “igraph”, and “magrittr”. 25 …”

Section: Methodsmentioning

confidence: 99%

The Comprehensive Role of High Mobility Group Box 1 (HMGB1) Protein in Different Tumors: A Pan-Cancer Analysis

Guan¹,

Zhong²,

Ma³

et al. 2023

JIR

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Background HMGB1 is a highly conserved nuclear protein widely expressed in mammalian cells. This study aimed to comprehensively investigate the roles and mechanisms of HMGB1 in different tumors. Methods Original data on HMGB1 expression, localization, potential interacting proteins, genetics were obtained from The Cancer Genome Atlas, Genotype-Tissue Expression, Cancer Cell Line Encyclopedia, Human Protein Atlas, Compartmentalized Protein-Protein Interaction and cBioPortal databases. Then, correlation between HMGB1 expression levels and tumor stage, prognosis, potential pathways, tumor microenvironment, ESTIMATE score, immune-related genes, immune cell infiltration, microsatellite instability, tumor mutation burden, or anti-tumor drug resistance was investigated. The above results consistently indicated that high expression of HMGB1 protein may be related to clinical prognosis of HCC patients. Therefore, clinical tissues of HCC patients were selected to verify the differential expression of HMGB1 protein in HCC. The sensitivity of HMGB1-siRNA transfected HepG2 cells to sorafenib was assessed. Results HMGB1 was found to be differentially expressed in many tumors and normal tissues. HMGB1 was mainly located in the nucleus and might interact with proteins such as TLR2 and TLR4. Furthermore, HMGB1 expression was closely related to tumor stage, prognosis, tumor microenvironment, immune-related genes, immune cell infiltration, microsatellite instability, tumor mutation burden, and anti-tumor drug resistance and might be involved in different pathways of various tumors. Immunohistochemistry results further verified the differential expression of HMGB1 in HCC and paracancerous tissues. HMGB1-siRNA transfected HepG2 cells had a tendency to be more insensitive to sorafenib treatment compared to the control group. Conclusions HMGB1 was differentially expressed in most tumors and normal tissues, and was closely related to the clinical stage, prognosis, immune infiltration, tumor microenvironment, and drug resistance of tumors. Therefore, HMGB1 may serve as a novel biomarker for predicting tumor prognosis, efficacy of immune checkpoint inhibitors, and a potential target for anti-tumor therapy.

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“…A comparative study of normal tissues and cancers revealed the expression of TMEM91 was strongly different. The data extracted from TCGA and GTE X indicated that the expression difference was signi cant for 31 of the 33 cancer types [19] . The expression level of TMEM91 in most tumors were lower when compared to normal tissues except that higher expression lever in head and neck cancer (HNSC), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), pancreatic adenocarcinoma (PAAD), and cholangiocarcinoma (CHOL).…”

Section: The Expression Levels Of Tmem91 Are Aberrant Across Various ...mentioning

confidence: 99%

A Pan-cancer Analysis of the Role of the Transmembrane Protein 91(TMEM91) in Human Tumors

Jiang

Song

2023

Preprint

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Transmembrane protein 91(TMEM91) encodes a protein belonging to the transmembrane protein family which mediates many human physiological processes, such as the regulation of cell migration and invasion, and participates in the immune response. At present, research on the TMEM family members focuses mostly on the field of molecular mechanisms, and the role of TMEM91 in tumor cells is still unrecognized. Using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, we can analysis the expression of TMEM91 in various tumors. The Kaplan-Meier method was used for the evaluation of the prognostic significance of TMEM91 in patients with pan-cancer. The dif-ferential expression of TMEM91 in diverse cancers with different clinical characteristics was analyzed with the UALCAN database. TIMER was used to explore how TMEM91 correlates with immune infiltration. The correlations between TMEM91 expression immune checkpoint (ICP), tumor mutational burden (TMB), and microsatellite instability (MSI) in human cancers were analyzed via the SangerBox database. Gene Set Cancer Analysis (GSCA) platform was used to investigate the correlation between TMEM91 expression with Copy number variations (CNV) and methylation. Protein-Protein Interaction analysis was performed in the GeneMANIA database. Gene Ontology and Kyoto Encyclopedia of Genes pathway en-richment analyses were further conducted for exploration of TMEM91 function. According to the finding of this study, downregulated TMEM91 expression was observed in numerous tumor tissues. The low TMEM91 expression group showed poor overall survival (OS) and disease-free survival (DFS). TMEM91 was positively correlated with can-cer-associated fibroblast (CAF), and nature killer T cell (NKT), and negatively correlated with CD4 + T cells, B cells and common lymphoid progenitor (CLP). Here, we show that there is a positive relationship between Contingent Negative Variation (CNV) and expression of TMEM91, whereas the correlation of TMEM91 expression with DNA methylation was nega-tive in all cases. Molecular biology experiments were performed to confirm the tumor pro-moting role of TMEM91 in glioma. Function analysis showed that TMEM91 expres-sion-related genes were mainly enriched in response to type I interferon /regulation of viral genome replication/negative regulation of viral process/movement in host environment. In addition, the association between the expression of TMEM91 and the use of the anticancer drug, sensitive anti-tumor drug based on CellMiner were predicted, such as the anticancer drug AS-703569, Hydroxyurea. Our pan-cancer analysis provides a deep understanding of the functions of TMEM91.TMEM91 may affect the oncogenesis and metastasis in different cancers via mediating the immune infiltrating cells and the degree of methylation. This study sheds new light on the mechanism of TMEM family in cancer.

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Sperm Autoantigenic Protein 17 Predicts the Prognosis and the Immunotherapy Response of Cancers: A Pan-Cancer Analysis

Cited by 10 publications

References 66 publications

ALKBH5 is a prognostic factor and promotes the angiogenesis of glioblastoma

ALKBH5 is a prognostic factor and promotes the angiogenesis of glioblastoma

The Comprehensive Role of High Mobility Group Box 1 (HMGB1) Protein in Different Tumors: A Pan-Cancer Analysis

A Pan-cancer Analysis of the Role of the Transmembrane Protein 91(TMEM91) in Human Tumors

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