scholarly journals Pan-Cancer Analysis of the Solute Carrier Family 39 Genes in Relation to Oncogenic, Immune Infiltrating, and Therapeutic Targets

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Yuan Qu ◽  
Rong-Yan Guo ◽  
Meng-Ling Luo ◽  
Quan Zhou
Keyword(s):  
Tumor Cell ◽  
Cancer Progression ◽  
Therapeutic Targets ◽  
Genetic Mutation ◽  
Functional Enrichment ◽  
Solute Carrier Family ◽  
Clinical Prognosis ◽  
Immune Infiltration ◽  
Solute Carrier ◽  
Pan Cancer

Background: Emerging pieces of evidence demonstrated that the solute carrier family 39 (SLC39A) members are critical for the oncogenic and immune infiltrating targets in multiple types of tumors. However, the precise relationship between the SLC39A family genes and clinical prognosis as well as the pan-cancer tumor cell infiltration has not been fully elucidated.Methods: In this study, the pan-cancer expression profile, genetic mutation, prognostic effect, functional enrichment, immune infiltrating, and potential therapeutic targets of the SLC39A family members were investigated by analyzing multiple public databases such as the Oncomine, TIMER, GEPIA, cBioPortal, KM-plotter, PrognoScan, GeneMANIA, STRING, DAVID, TIMER 2.0, and CellMiner databases.Results: The expression levels of most SLC39 family genes in the tumor tissues were found to be significantly upregulated compared to the normal group. In mutation analysis, the mutation frequencies of SLC39A4 and SLC39A1 were found to be higher among all the members (6 and 4%, respectively). Moreover, the overall mutation frequency of the SLC39A family genes ranged from 0.8 to 6% pan-cancer. Also, the function of the SLC39A highly related genes was found to be enriched in functions such as zinc II ion transport across the membrane, steroid hormone biosynthesis, and chemical carcinogenesis. In immune infiltration analysis, the expression level of the SLC39A family genes was found to be notably related to the immune infiltration levels of six types of immune cells in specific types of tumors. In addition, the SLC39A family genes were significantly related to the sensitivity or resistance of 63 antitumor drugs in a variety of tumor cell lines.Conclusion: These results indicate that the SLC39 family genes are significant for determining cancer progression, immune infiltration, and drug sensitivity in multiple cancers. This study, therefore, provides novel insights into the pan-cancer potential targets of the SLC39 family genes.

scholarly journals Prognostic and immunological value of LTB4R in pan-cancer

2021 ◽  
Vol 18 (6) ◽  
pp. 9336-9356
Author(s):  
Sidan Long ◽  
◽  
Shuangshuang Ji ◽  
Kunmin Xiao ◽  
Peng Xue ◽  
...  
Keyword(s):  
Immune Cells ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Negative Influence ◽  
Leukotriene B4 ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Significant Difference ◽  
Pan Cancer

<abstract> <sec><title>Background</title><p>LTB4 receptor 1 (LTB4R), as the high affinity leukotriene B4 receptor, is rapidly revealing its function in malignancies. However, it is still uncertain.</p> </sec> <sec><title>Methods</title><p>We investigated the expression pattern and prognostic significance of LTB4R in pan-cancer across different databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter, in this study. Meanwhile, we explored the significance of LTB4R in tumor metastasis by HCMDB. Then functional enrichment analysis of related genes was performed using GeneMANIA and DAVID. Lastly, utilizing the TIMER datasets, we looked into the links between LTB4R expression and immune infiltration in malignancies.</p> </sec> <sec><title>Results</title><p>In general, tumor tissue displayed higher levels of LTB4R expression than normal tissue. Although LTB4R had a negative influence on pan-cancer, a high expression level of LTB4R was protective of LIHC (liver hepatocellular carcinoma) patients' survival. There was no significant difference in the distribution of LTB4R between non-metastatic and metastatic tumors. Based on Gene Set Enrichment Analysis, LTB4R was implicated in pathways involved in inflammation, immunity, metabolism, and cancer diseases. The correlation between immune cells and LTB4R was found to be distinct across cancer types. Furthermore, markers of infiltrating immune cells, such as Treg, T cell exhaustion and T helper cells, exhibited different LTB4R-related immune infiltration patterns.</p> </sec> <sec><title>Conclusion</title><p>The LTB4R is associated with immune infiltrates and can be used as a prognostic biomarker in pan-cancer.</p> </sec> </abstract>

scholarly journals Prognostic Value of MUC1 and its Correlation with Tumor-Infiltrating Immune Cells in Breast Cancer

2021 ◽  
Author(s):  
Xiaomin Xi ◽  
Yilin You ◽  
Weidong Huang ◽  
jicheng zhan
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Progression ◽  
Macrophage Polarization ◽  
Muc1 Expression ◽  
Breast Cancer Patients ◽  
Gene Markers ◽  
Clinical Prognosis ◽  
Luminal B ◽  
Immune Infiltration

Abstract Background: MUC1 is a transmembrane glycoprotein, aberrantly glycosylated and overexpressed in a variety of epithelial cancers, and plays a crucial role in cancer progression, especially in breast cancer. It is also an essential regulator for immune functionality, but the mechanisms whereby it effects immune infiltration in breast cancer remain uncertain. Methods: In this research, MUC1 expression was analyzed by the Oncomine and TIMER database. The association between MUC1 and prognosis was evaluated by Kaplan-Meier plotter database. The correlations of MUC1 with immune infiltration and immunological markers were assessed by TIMER database. Results: We found that MUC1 expression was significantly correlated with outcomes in multiple cancers, with the effect being particularly pronounced in breast cancer. Pathologically, elevated MUC1 expression was related with worse prognosis depending on intrinsic subtypes, ER status, patient stage, lymph node and TP53 mutation status in breast cancer. Specifically, low level of MUC1 seemed to be more favorable to luminal B patients with systemic treatment. MUC1 expression had significant negative correlations with infiltrating levels of CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, monocytes and dendritic cells (DCs) in breast cancer. Besides, MUC1 displayed strong regulations on macrophage polarization and diverse immunological gene markers. The patients with lower MUC1 and deeper immune infiltration predicted better prognosis. Conclusions: MUC1 is significantly associated with clinical prognosis and potentially plays an essential role in modulating cytotoxic T lymphocytes (CTLs), tumor associated macrophages (TAMs), natural killer cells (NK cells) and DCs in breast tumors. Collectively, MUC1 could be served as a valuable biomarker of predicting prognosis and immune infiltration for breast cancer patients.

scholarly journals An Integrative Pan-Cancer Analysis Revealing LCN2 as an Oncogenic Immune Protein in Tumor Microenvironment

2020 ◽  
Vol 10 ◽  
Author(s):  
Wen-Xiu Xu ◽  
Jian Zhang ◽  
Yu-Ting Hua ◽  
Su-Jin Yang ◽  
Dan-Dan Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Cytochrome P450 ◽  
Interaction Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Sterile Inflammation ◽  
Lipocalin 2 ◽  
Immune Infiltration ◽  
Pan Cancer

BackgroundLipocalin 2 (LCN2), an innate immune protein, plays a pivotal role in promoting sterile inflammation by regulating immune responses. However, the role of LCN2 in diverse cancers remains poorly defined. This research aimed to investigate the correlation between LCN2 expression and immunity and visualize its prognostic landscape in pan-cancer.MethodsRaw data in regard to LCN2 expression in cancer patients were acquired from TCGA and GTEx databases. Besides, we investigated the genomic alterations, expression pattern, and survival analysis of LCN2 in pan-cancer across numerous databases, including cBioPortal and GEPIA database. The correlation between LCN2 expression and tumor immune infiltration was explored via TIMER, and we utilized CIBERSORT and ESTIMATE computational methods to assess the proportion of tumor-infiltrating immune cells (TIICs) and the amount of stromal and immune components from TCGA database. Protein–Protein Interaction analysis was performed in GeneMANIA database, and gene functional enrichment was performed by Gene Set Enrichment Analysis (GSEA).ResultsOn balance, tumor tissue had a higher LCN2 expression level compared with that in normal tissue. Elevated expression of LCN2 was related to poor clinical regimen with OS and RFS. There were significant positive correlations between LCN2 expression and TIICs, including CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. Moreover, markers of TIICs exhibited different LCN2-related immune infiltration patterns. GSEA analysis showed that the expression of LCN2 was related to retinol metabolism, drug metabolism cytochrome P450 and metabolism of xenobiotics by cytochrome P450.ConclusionsThese findings suggested that LCN2 might serve as a biomarker for immune infiltration and poor prognosis in cancers, shedding new light on therapeutics of cancers.

scholarly journals A Pan-Cancer Analysis of SLC12A5 Reveals Its Correlations with Tumor Immunity

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yi Jiang ◽  
Hong-li Liao ◽  
Li-ya Chen
Keyword(s):  
Tumor Immunity ◽  
Tumor Stage ◽  
Mechanisms Of Action ◽  
Solute Carrier Family ◽  
Tumor Mutation Burden ◽  
Human Cancers ◽  
Mutation Burden ◽  
Solute Carrier ◽  
Pan Cancer ◽  
Disease Specific

Background. Solute carrier family 12 member 5 (SLC12A5) has been reported to play an oncogenic role in certain malignancies. Its prognostic roles and immune mechanisms of action in human cancers, however, remain largely unknown. Methods. Data derived from TCGA, GEPIA, and TIMER databases were utilized to delve into the expressing patterns, prognostic values, clinical significances, and tumor immunity of SLC12A5 in tumors. Additionally, the association of SLC12A5 expressions with tumor mutation burden (TMB), methyltransferases, and mismatch repairs (MMRs) was also analyzed. Results. Herein, we observed that SLC12A5 was significantly overexpressed in various malignancies, and SLC12A5 levels correlated with overall survival, disease-specific survival, and tumor stage of certain cancers. Furthermore, we noticed that SLC12A5 was distinctly associated with methyltransferases, mismatch repair proteins, TMB, and MSI in human cancers. Conclusions. SLC12A5 may act as a potential prognostic and immunological biomarker and therapeutic target for human cancers.

scholarly journals PPP1R14B Is a Prognostic and Immunological Biomarker in Pan-Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingxia Deng ◽  
Long Peng ◽  
Jiamin Li ◽  
Xiong Liu ◽  
Xichun Xia ◽  
...  
Keyword(s):  
Survival Rates ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Clinical Prognosis ◽  
Immune Infiltration ◽  
Myeloid Derived Suppressor Cell ◽  
Tumor Tissues ◽  
Tumor Types ◽  
The Relationship ◽  
Pan Cancer

Recent studies have shown that PPP1R14B was highly expressed in tumor tissues and patients with high expression of PPP1R14B had poor survival rates. However, the function and mechanisms of PPP1R14B in tumor progression remain ill defined. There was also lack of pan-cancer evidence for the relationship between PPP1R14B and various tumor types based on abundant clinical data. We used the TCGA project and GEO databases to perform pan-cancer analysis of PPP1R14B, including expression differences, correlations between expression levels and survival, genetic alteration, immune infiltration, and relevant cellular pathways, to investigate the functions and potential mechanisms of PPP1R14B in the pathogenesis or clinical prognosis of different cancers. Herein, we found that PPP1R14B was involved in the prognosis of pan-cancer and closely related to immune infiltration. Increased PPP1R14B expression correlated with poor prognosis and increased immune infiltration levels in myeloid-derived suppressor cells (MDSCs). Our studies suggest that PPP1R14B can be used as a prognostic biomarker for pan-cancer. Our findings may provide an antitumor strategy targeting PPP1R14B, including manipulation of tumor cell growth or the tumor microenvironment, especially myeloid-derived suppressor cell infiltration.

miR-142-3p Regulates Tumor Cell Autophagy and Promotes Colon Cancer Progression by Targeting TP53INP2

Chemotherapy ◽  
2021 ◽  
Author(s):  
Jiujian Zheng ◽  
Chuan Cheng ◽  
Jie Xu ◽  
Peng Gao ◽  
Jianping Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Cell ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Hedgehog Signaling ◽  
Therapeutic Targets ◽  
Gene Set Enrichment Analysis ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Hedgehog Signaling Pathway

Objectives: Colon cancer (CC) is the third largest cancer worldwide. Investigation of the molecular mechanism of CC progression helps to explore novel therapeutic targets. We attempted to understand the modulatory mechanism of miR-142-3p in CC cell autophagy and CC progression, which will lay a theoretical groundwork for seeking potential diagnostic and therapeutic targets for CC. Methods: Through bioinformatics methods, miRNA expression data were subjected to differential analysis for identification of target miRNA. Downstream target mRNAs were predicted and gene set enrichment analysis (GSEA) was completed. qRT-PCR assessed gene expression in cells. Cell Counting Kit-8, cell doubling time calculation, colony formation, and flow cytometry were used to assess cellular biological functions. Dual-luciferase assay was used for targeting relationship validation of the target miRNA and mRNA. Western blot was performed to evaluate expression of proteins related to HEDGEHOG signaling pathway and autophagy. Results: miR-142-3p was markedly highly expressed in CC, and high miR-142-3p expression in CC patients was implicated with relatively poor prognosis. Over-expressing miR-142-3p facilitated proliferation and inhibited apoptosis of CC cells, whereas silencing it produced an opposite result. miR-142-3p targeted and decreased TP53INP2 level. TP53INP2 over-expression suppressed the HEDGEHOG signaling pathway and induced the activation of CC cell autophagy. Rescue experiments revealed that influence of miR-142-3p inhibitor on CC cell proliferation and apoptosis could be reversed by silencing TP53INP2. Conclusion: miR-142-3p hampered tumor cell autophagy and promoted CC progression via targeting TP53INP2, which will offer a fresh research orientation for the diagnosis of CC.

scholarly journals SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Suhong Xia ◽  
Jingwen Wu ◽  
Wangdong Zhou ◽  
Mingyu Zhang ◽  
Kai Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Immune Escape ◽  
Significant Risk ◽  
Suppressor Cells ◽  
Significant Risk Factor ◽  
Solute Carrier Family ◽  
Invasion And Metastasis ◽  
Solute Carrier

AbstractThe main reason for poor prognosis in hepatocellular carcinoma (HCC) patients is high metastasis and recurrence. Cancer progression depends on a tumor-supportive microenvironment. Therefore, illustrating the mechanisms of tumor immunity in underlying HCC metastasis is essential. Here, we report a novel role of solute carrier family 7 member 2 (SLC7A2), a member of the solute carrier family, in HCC metastasis. The reduction of SLC7A2 was an independent and significant risk factor for the survival of HCC patients. Upregulation of SLC7A2 decreased HCC invasion and metastasis, whereas downregulation of SLC7A2 promoted HCC invasion and metastasis. We further found that deficient SLC7A2 medicated the upregulation of CXCL1 through PI3K/Akt/NF-kκB pathway to recruit myeloid-derived suppressor cells (MDSCs), exerting tumor immunosuppressive effect. Moreover, we found that G9a-mediated di-methylation of H3K9 (H3K9me2) silenced the expression of SLC7A2 to suppress HCC metastasis and immune escape. In conclusion, G9a-mediated silencing of SLC7A2 exerts unexpected functions in cancer metastasis by fostering a tumor-supportive microenvironment through CXCL1 secretion and MDSCs recruitment. Thus, SLC7A2 may provide new mechanistic insight into the cancer-promoting property of MDSCs.

scholarly journals Genomic analysis and clinical implications of immune cell infiltration in gastric cancer

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Ming Wu ◽  
Yadong Wang ◽  
Hang Liu ◽  
Jukun Song ◽  
Jie Ding
Keyword(s):  
Gastric Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
R Package ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Cell Type ◽  
Clinical Prognosis ◽  
Immune Infiltration

Abstract The immune infiltration of patients with gastric cancer (GC) is closely associated with clinical prognosis. However, previous studies failed to explain the different subsets of immune cells involved in immune responses and diverse functions. The present study aimed to uncover the differences in immunophenotypes in a tumor microenvironment (TME) between adjacent and tumor tissues and to explore their therapeutic targets. In our study, the relative proportion of immune cells in 229 GC tumor samples and 22 paired matched tissues was evaluated with a Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) algorithm. The correlation between immune cell infiltration and clinical information was analyzed. The proportion of 22 immune cell subsets was assessed to determine the correlation between each immune cell type and clinical features. Three molecular subtypes were identified with ‘CancerSubtypes’ R-package. Functional enrichment was analyzed in each subtype. The profiles of immune infiltration in the GC cohort from The Cancer Genome Atlas (TCGA) varied significantly between the 22 paired tissues. TNM stage was associated with M1 macrophages and eosinophils. Follicular helper T cells were activated at the late stage. Monocytes were associated with radiation therapy. Three clustering processes were obtained via the ‘CancerSubtypes’ R-package. Each cancer subtype had a specific molecular classification and subtype-specific characterization. These findings showed that the CIBERSOFT algorithm could be used to detect differences in the composition of immune-infiltrating cells in GC samples, and these differences might be an important driver of GC progression and treatment response.

scholarly journals An Integrative Prognostic and Immune Analysis of PTPRD in Pan-Cancer

2021 ◽  
Author(s):  
Chunpei Ou ◽  
Qin Peng ◽  
Changchun Zeng
Keyword(s):  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Cancer Therapeutics ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Biological Processes ◽  
Immune Infiltration ◽  
The Relationship ◽  
Pan Cancer

Abstract Background: PTPRD plays an indispensable role in the occurrence of multiple tumors. However, pan-cancer analysis is unavailable. The purpose of this research was to investigate the relationship between PTPRD and immunity and describe its prognostic landscape across various tumors. Methods: We explored expression profile, survival analysis, and genomic alterations of PTPRD based on the TIMER, GEPIA, UALCAN, PrognoScan, and cBioPortal database. The frequency of PTPRD mutation and its correlation with response to immunotherapy were evaluated using the cBioPortal database. The relationship between PTPRD and immune-cell infiltration was analyzed by the TIMER and TISIDB databases. A protein interaction network was constructed by the STRING database. GO and KEGG enrichment analysis was executed by the Metascape database.Results: A significant correlation between PTPRD expression and prognosis was found in various cancers. Aberrant PRPRD expression was closely related to immune infiltration. Importantly, the patients who harbored PTPRD mutation and received immune checkpoint inhibitors had worse overall survival, especially in non-small cell lung cancer and melanoma, and had a higher TMB score. Moreover, PTPRD mutation was involved in numerous biological processes, including immunological signaling pathways. Additionally, a PTPRD protein interaction network was constructed, and genes that interacted with PTPRD were identified. Functional enrichment analysis demonstrated that a variety of GO biological processes and KEGG pathways of PTPRD were primarily involved in the therapeutic mechanisms. Conclusions: These results revealed that PRPRD might function as a biomarker for prognosis and immune infiltration in cancers, throwing new light on cancer therapeutics.

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