Systematic Analysis Uncovers Associations of PGK1 with Prognosis and Immunological Characteristics in Breast Cancer

Objective. Phosphoglycerate kinase 1 (PGK1) is an essential enzyme in the process of glycolysis and mitochondrial metabolism. Herein, we conducted a systematic analysis to uncover the clinical implication of PGK1 deregulation in breast cancer. Methods. Expression pattern and prognostic significance of PGK1 were comprehensively assessed across pan-cancer based on RNA-seq profiles from the TCGA project. Associations of PGK1 with immunological features in the tumor microenvironment (immune checkpoints, immune response predictors (tumor mutation burden (TMB) and microsatellite instability (MSI)), and tumor-infiltrating immune cells) were systematically analyzed. The role of PGK1 in the prediction of breast cancer prognosis was also evaluated. GSEA was presented for investigating biological pathways involved in PGK1. Results. PGK1 was specifically overexpressed in most of cancer types, including breast cancer. High PGK1 expression was indicative of undesirable overall survival, progression-free interval, disease-specific survival, and disease-free interval for various cancers. Furthermore, high PGK1 levels exhibited prominent correlations to immune checkpoints and high response to immunotherapy across pan-cancer. Notably, ROC curves confirmed that PGK1 can robustly predict breast cancer prognosis. Furthermore, PGK1 might shape an inflamed tumor microenvironment following the evidence that PGK1 was positively correlated to the abundance levels of tumor-infiltrating immune cells such as CD8+ T cell and NK cell in breast cancer. GSEA results revealed that PGK1 participated in metabolism and carcinogenic pathways. Conclusion. Collectively, PGK1 was capable of robustly predicting the prognosis and response to cancer immunotherapy in breast cancer.

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The Prognostic Significance of Phosphatase and Tensin Homolog Loss in Breast Cancer

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.757 ◽

2019 ◽

Vol 7 (21) ◽

pp. 3716-3720

Author(s):

Indri Windarti ◽

Wirsma Arif Harahap ◽

Ricvan Dana Nindrea ◽

Eti Yerizel ◽

Primaria Dewi Rustamadji

Keyword(s):

Breast Cancer ◽

Meta Analysis ◽

Random Effect ◽

Prognostic Significance ◽

Breast Cancer Prognosis ◽

Cancer Prognosis ◽

Breast Cancer Patients ◽

Phosphatase And Tensin Homolog ◽

Pten Loss ◽

Tensin Homolog

AIM: This study aims to determine the prognostic significance of phosphatase and tensin homolog (PTEN) loss in breast cancer. METHODS: We conducted a meta-analysis study. Sample of this study were research articles that evaluated PTEN loss and prognosis in breast cancer patients. We searched for relevant studies published in PubMed and Proquest from January 2010 to July 2018. We reviewed studies that examined the association between immunohistochemical expression of PTEN and breast cancer prognosis using meta-analysis methods. Pooled risk ratios (RR) were calculated using fixed and random-effect models. Data were processed using Review Manager 5.3 (RevMan 5.3). RESULTS: There were 7 studies conducted a systematic review then continued to evaluate the association of PTEN loss and breast cancer prognosis by meta-analysis. There was a significant association of PTEN loss with poor prognosis of breast cancer (RR = 0.76 [95% CI 0.59-0.98 p <0.07), and there was not any significant publication bias for studies included. CONCLUSION: This study confirmed PTEN loss is an important independent factor for breast cancer prognosis.

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A Comprehensive Prognostic and Immune Analysis of SLC41A3 in Pan-Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.586414 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jun Liu ◽

Shanqiang Zhang ◽

Wenjie Dai ◽

Chongwei Xie ◽

Ji-Cheng Li

Keyword(s):

Overall Survival ◽

Immune Cells ◽

Cox Regression ◽

Expression Profiles ◽

Prognostic Significance ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Cox Regression Analysis ◽

Pan Cancer

SLC41A3, as a member of the 41st family of solute carriers, participates in the transport of magnesium. The role of SLC41A3 in cancer prognosis and immune regulation has rarely been reported. This study was designed to analyze the expression status and prognostic significance of SLC41A3 in pan-cancers. The mRNA expression profiles of SLC41A3 were obtained from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), the Broad Institute Cancer Cell Line Encyclopedia (CCLE), and the International Cancer Genome Consortium (ICGC). The Cox regression and Kaplan-Meier analyses were used to evaluate the prognostic value of SLC41A3 in pan-cancer. Furthermore, the correlation between SLC41A3 expression and immune cells infiltration, immune checkpoint, mismatch repair (MMR), DNA methyltransferase (DNMT), tumor mutation burden (TMB), and microsatellite instability (MSI) were calculated using data form TCGA database. The results showed that the expression of SLC41A3 was down-regulated in kidney renal clear cell carcinoma (KIRC), and was associated with poor overall survival and tumor-specific mortality. Whereas, the expression of SLC41A3 was up-regulated in liver hepatocellular carcinoma (LIHC), and the results of Cox regression analysis revealed that SLC41A3 was an independent factor for LIHC prognosis. Meanwhile, a nomogram including SLC41A3 and stage was built and exhibited good predictive power for the overall survival of LIHC patients. Additionally, correlation analysis suggested a significant correlation between SLC41A3 and TMB, MSI, MMR, DNMT, and immune cells infiltration in various cancers. The overall survival and disease-specific survival analysis revealed that the combined SLC41A3 expression and immune cell score, TMB, and MSI were significantly associated with clinical outcomes in ACC, LIHC, and UVM patients. Therefore, we proposed that SLC41A3 may serve as a potential prognostic biomarker for cancer.

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Systematic Profiling of Diagnostic and Prognostic Value of Autophagy-Related Genes for Sarcoma Patients

10.21203/rs.3.rs-76971/v1 ◽

2020 ◽

Author(s):

Yuanhe Wang ◽

Jianyi Li ◽

Cheng Shao ◽

Xiaojie Tang ◽

Yukun Du ◽

...

Keyword(s):

Tumor Microenvironment ◽

Immune Cells ◽

Disease Free Survival ◽

Independent Set ◽

Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Differentially Expressed ◽

Immune Checkpoints ◽

Systematic Analysis

Abstract Background: Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking.Methods: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. Results: In total, 84 DEIRGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between twp clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.636 for the OS and DFS nomograms, respectively.Conclusion: This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.

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A High Epigenetic Risk Score Shapes the Non-Inflamed Tumor Microenvironment in Breast Cancer

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.675198 ◽

2021 ◽

Vol 8 ◽

Author(s):

Dong Zhang ◽

Yingnan Wang ◽

Qifeng Yang

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

High Risk ◽

Tumor Microenvironment ◽

Risk Score ◽

Immune Cells ◽

Immune Checkpoints ◽

Cancer Immunity ◽

Anti Cancer ◽

Risk Patients

Background: Epigenetic dysregulation via aberrant DNA methylation has gradually become recognized as an efficacious signature for predicting tumor prognosis and response to therapeutic targets. However, reliable DNA methylation biomarkers describing tumorigenesis remain to be comprehensively explored regarding their prognostic and therapeutic potential in breast cancer (BC).Methods: Whole-genome methylation datasets integrated from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were profiled (n = 1,268). A three-stage selection procedure (discovery, training, and external validation) was utilized to screen out the prominent biomarkers and establish a robust risk score from more than 300,000 CpG sites after quality control, rigorous filtering, and reducing dimension. Moreover, gene set enrichment analyses guided us to systematically correlate this epigenetic risk score with immunological characteristics, including immunomodulators, anti-cancer immunity cycle, immune checkpoints, tumor-infiltrating immune cells and a series of signatures upon modulating components within BC tumor microenvironment (TME). Multi-omics data analyses were performed to decipher specific genomic alterations in low- and high-risk patients. Additionally, we also analyzed the role of risk score in predicting response to several treatment options.Results: A 10-CpG-based prognostic signature which could significantly and independently categorize BC patients into distinct prognoses was established and sufficiently validated. And we hypothesize that this signature designs a non-inflamed TME in BC based on the evidence that the derived risk score is negatively correlated with tumor-associated infiltrating immune cells, anti-cancer immunity cycle, immune checkpoints, immune cytolytic activity, T cell inflamed score, immunophenoscore, and the vast majority of immunomodulators. The identified high-risk patients were characterized by upregulation of immune inhibited oncogenic pathways, higher TP53 mutation and copy number burden, but lower response to cancer immunotherapy and chemotherapy.Conclusion: Our work highlights the complementary roles of 10-CpG-based signature in estimating overall survival in BC patients, shedding new light on investigating failed events concerning immunotherapy at present.

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Systematic profiling of diagnostic and prognostic value of autophagy-related genes for sarcoma patients

BMC Cancer ◽

10.1186/s12885-020-07596-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuanhe Wang ◽

Jianyi Li ◽

Cheng Shao ◽

Xiaojie Tang ◽

Yukun Du ◽

...

Keyword(s):

Tumor Microenvironment ◽

Immune Cells ◽

Disease Free Survival ◽

Independent Set ◽

Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Differentially Expressed ◽

Immune Checkpoints ◽

Systematic Analysis

Abstract Background Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking. Methods Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. Results In total, 84 DEARGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between two clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.747 for the OS and DFS nomograms, respectively. Conclusion This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.

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The Prognostic Significance of MACC1 Expression in Breast Cancer and Its Relationship to Immune Cells in the Tumor Microenvironment and Patient Survival

Medicina ◽

10.3390/medicina57090934 ◽

2021 ◽

Vol 57 (9) ◽

pp. 934

Author(s):

Dina A. Ali ◽

Dina M. El-Guindy ◽

Mohamed A. Elrashidy ◽

Nesreen M. Sabry ◽

Ahmed M. Kabel ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Tumor Microenvironment ◽

Immune Cells ◽

Lymphovascular Invasion ◽

Prognostic Significance ◽

Progression Free Survival ◽

Mrna Levels ◽

Free Survival ◽

Invasion Stage

Breast cancer (BC) is one of the most prevalent malignancies among females worldwide. Globally, distant metastases were reported to be responsible for a large proportion of breast cancer-related deaths. The metastasis-associated colon cancer-1 (MACC1) gene was reported as a reliable biomarker for early detection of metastasis and prediction of prognosis of breast cancer. This study investigated the prognostic significance of MACC1 in breast cancer in relation to the clinicopathologic characteristics and patients’ survival. Furthermore, the possible correlation between MACC1 expression and the different immune cells in the tumor microenvironment was explored. MACC1 mRNA was identified using quantitative reverse transcription polymerase chain reaction in 120 breast cancer specimens and adjacent non-cancerous tissues. MACC1 mRNA expression was significantly higher in the cancerous relative to the non-cancerous tissues (p < 0.001). High MACC1 expression was significantly associated with poor prognostic parameters, such as larger tumor size, grade III tumors, positive nodal metastasis, lymphovascular invasion, stage III tumors, and elevated Ki-67 expression. Higher MACC1 mRNA levels were positively correlated with CD163+ tumor-associated macrophages (r = 0.614, p < 0.001), and were negatively correlated with CD56+ natural killer cells (r = −0.398, p < 0.001) and CD8+ cytotoxic T lymphocytes (r = −0.323, p < 0.001). MACC1 expression was associated with poor patient overall survival (OS) and progression-free survival (PFS) (p < 0.001). Multivariate analysis suggested that MACC1 expression and the presence of lymphovascular invasion could be independent prognostic indicators for breast cancer (p = 0.015 and 0.042, respectively). In conclusion, MACC1 is highly expressed in cancerous tissues and is significantly related to poor prognostic factors, overall survival, and progression-free survival. MACC1 may influence infiltration of the immune cells in the tumor microenvironment, enhance immune escape of tumor cells, and may serve as a reliable independent prognostic factor for breast cancer.

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