Genetic associations of T cell cancer immune response with tumor aggressiveness in localized prostate cancer patients and disease reclassification in an active surveillance cohort

Wang, Qinchuan; Gregg, Justin R.; Gu, Jian; Ye, Yuanqing; Chang, David W.; Davis, John W.; Thompson, Timothy C.; Kim, Jeri; Logothetis, Christopher J.; Wu, Xifeng

doi:10.1080/2162402x.2018.1483303

Cited by 9 publications

(6 citation statements)

References 42 publications

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“…Immunoproteasome-mediated proteolysis generates immunogenic epitopes presented by major histocompatibility complex (MHC) class I molecules. we have already confirmed the role of PSMB8 in the evolution of cutaneous squamous cell carcinoma, papillary thyroid carcinoma, and prostate adenocarcinoma, ( 13 - 15 ), In addition to the previously mentioned tumors, PSMB8 plays an inhibiting neovascularization role in glioma by regulating ERK1/2 and PI3K/AKT signaling pathways ( 16 , 17 ). These findings elucidate that the expression of PSMB8 is associated with multiple immune-related pathways in vivo, and that the gene may act as a powerful biomarker to determine the prognosis of a variety of cancers.…”

Section: Resultssupporting

confidence: 77%

“…Another study on the functions of PSMB8 in the pathogenesis of mucinous ovarian cancer has confirmed that PSMB8 is an intermediary between the presentation of foreign antigens by MHC - I molecules and the irregular nuclear factor-light chain enhancer ( Nik/NF - kB ) pathway of activated B cells ( 27 ). Additionally, PSMB8 is involved in activating the PI3K/AKT pathway in acute myelogenous leukemia ( 28 ), and several studies have reported its contribution to the progression of cutaneous squamous cancer, papillary thyroid cancer, and prostate cancer ( 13 - 15 ). Several studies have proposed that PSMB8 works by promoting immune cell concentration.…”

Section: Discussionmentioning

confidence: 99%

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Bioinformatics analysis identifies PSMB8 as a key gene in the cutaneous malignant melanoma tumor microenvironment

Lin¹,

Yu²,

Wang³

et al. 2022

Ann Transl Med

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Background: Cutaneous tumors are commonly seen in clinical practice, and malignant melanoma (MM) is the leading cause of cutaneous tumor-induced death. The tumor microenvironment (TME), a critical part of tumorigenesis, has been a research hotspot in recent years. However, the effects of the MM microenvironment components remain elusive. This study aimed to analyze the various components in the TME of MM to identify factors affecting the tumorigenesis, progression, and metastasis of MM and the survival of MM patients. We also aimed to identify biomarkers related to TME rehabilitation to provide a new direction for MM treatment.Methods: We used bioinformatics to analyze the RNA-seq and somatic mutation data of 473 MM patients from The Cancer Genome Atlas database. Firstly, the patients' immunity and stroma were separately scored by the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) method. According to the median score, the participants were split into high-and low-score groups. Then, Gene Set Enrichment Analysis (GSEA) was performed, showing that high-expression genes were highly abundant in biological and metabolic activities associated with the immune system.Results: Differentially expressed genes (DEGs) and differentially mutated genes (DMGs) were identified and intersected to obtain the key immune-related genes PSMB8, FAM216B, DYSF, and FAM131C. PSMB8 was finally selected as the preferred immune-related prognostic marker; it was positively associated with overall survival and therefore considered a protective gene for MM patients. The GSEA analysis showed that PSMB8 with high expression had greater gene abundance in biological and metabolic processes related to immune system. In addition, CIBERSORT analysis showed an association between the proportion of tumorinfiltrating immune cells and PSMB8 expression.Conclusions: Our results suggest that PSMB8 might be associated with tumorigenesis and MM progression and could serve as a biomarker for the TME rehabilitation of MM. Our findings provide a new perspective and direction for the treatment of MM.

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Section: Resultssupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis identifies PSMB8 as a key gene in the cutaneous malignant melanoma tumor microenvironment

Lin¹,

Yu²,

Wang³

et al. 2022

Ann Transl Med

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“…Considering the relationship between Gleason scores (and BCR) and immune function ( 14 , 24 , 25 ), we evaluated the effect of COL5A2 on immune infiltration. Our results revealed that COL5A2 remarkably increased the numbers of macrophages, Th2 cells, and DCs in the tumors.…”

Section: Discussionmentioning

confidence: 99%

COL5A2 Promotes Proliferation and Invasion in Prostate Cancer and Is One of Seven Gleason-Related Genes That Predict Recurrence-Free Survival

et al. 2021

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Extensive research has revealed that the score derived from the Gleason grading system plays a pivotal role in predicting prostate cancer (PCa) progression. However, the underlying involvement of Gleason-related genes in PCa requires further investigation. This study aimed to identify Gleason-related genes with the potential to guide PCa therapy and future research. Differentially expressed genes (DEGs) were identified by comparing PCa tissues with high or low Gleason scores using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. R v3.6.1, SPSS v23, and ImageJ software were used for all analyses. An effective recurrence-free survival (RFS) predictive model based on seven Gleason-related genes was established and validated (TCGA, AUC = 0.803; five years, AUC = 0.740; three years, AUC = 0.722; one year, AUC = 0.711; GSE46602, AUC = 0.766; five years, AUC = 0.808; three years, AUC = 0.723; one year, AUC = 0.656; GSE116918, AUC = 0.788; five years, AUC = 0.704; three years, AUC = 0.693; one year, AUC = 0.996). Calibration and nomogram plots were conducted. Weighted correlation network analysis (WGCNA) was used, and COL5A2 was selected for further analysis. The results from in vitro experiments demonstrated that COL5A2 was upregulated in PCa with high Gleason scores. The knockdown of COL5A2 inhibited cell proliferation and invasion in PC-3 and LNCaP cell lines. Meanwhile, COL5A2 displayed a strong association with immune infiltration, which might be an underlying immunotherapy target for PCa. We successfully established a robust RFS predictive model. The findings from this study indicated that COL5A2 could promote cell proliferation and invasion in PCa.

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“…This study used data from a previously described cohort of patients with PCa enrolled at MDACC [ 10 , 11 ]. In brief, the cohort involved non-Hispanic white men with previously untreated PCa.…”

Section: Methodsmentioning

confidence: 99%

Immune checkpoint-related serum proteins and genetic variants predict outcomes of localized prostate cancer, a cohort study

Wang

et al. 2020

Cancer Immunol Immunother

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Background The clinical predictors and biological mechanisms for localized prostate cancer (PCa) outcomes remain mostly unknown. We aim to evaluate the role of serum immune-checkpoint-related (ICK) proteins and genetic variations in predicting outcomes of localized PCa. Methods We profiled the serum levels of 14 ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, 4-1BB, CD27, and CTLA-4) in 190 patients with localized PCa. The genotypes of 97 single nucleotide polymorphisms (SNPs) from 19 ICK-related genes were analyzed in an extended population (N = 1762). Meta-data from ArrayExpress and TCGA was employed to validate and to probe functional data. Patients were enrolled and tumor aggressiveness, biochemical recurrence (BCR), and progression information were obtained. Statistical analyses were performed analyzing associations between serum biomarkers, genotypes, mRNA and outcomes. Results We showed that serum (s)BTLA and sTIM3 levels were associated with PCa aggressiveness (P < 0.05). sCD28, sCD80, sCTLA4, sGITR, sHVEM and sIDO correlated with both BCR and progression risks (all P < 0.05). We further identified ICK variants were significantly associated with aggressiveness, BCR and progression. Among them, 4 SNPs located in CD80 (rs7628626, rs12695388, rs491407, rs6804441) were not only associated with BCR and progression risk, but also correlated with sCD80 level (P < 0.01). rs491407 was further validated in an independent cohort. The CD80 mRNA expression was associated with BCR (HR, 1.85, 95% CI 1.06–3.22, P = 0.03) in meta-analysis of validation cohorts. Conclusion We highlight the prognostic value of serum ICK-related proteins for predicting aggressiveness, BCR and progression of PCa. The genetic variations and mRNA expression in CD80 could be predictors and potential targets of localized PCa.

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Genetic associations of T cell cancer immune response with tumor aggressiveness in localized prostate cancer patients and disease reclassification in an active surveillance cohort

Cited by 9 publications

References 42 publications

Bioinformatics analysis identifies PSMB8 as a key gene in the cutaneous malignant melanoma tumor microenvironment

Bioinformatics analysis identifies PSMB8 as a key gene in the cutaneous malignant melanoma tumor microenvironment

COL5A2 Promotes Proliferation and Invasion in Prostate Cancer and Is One of Seven Gleason-Related Genes That Predict Recurrence-Free Survival

Immune checkpoint-related serum proteins and genetic variants predict outcomes of localized prostate cancer, a cohort study

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