scholarly journals Potential Prognosis and Diagnostic Value of AKT3, LSM12, MEF2C, and RAB30 in Exosomes in Colorectal Cancer on Spark Framework

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jue Wang ◽  
Sheng Wu ◽  
Jiuwen Zhang ◽  
Jing Chen
Keyword(s):  
Colorectal Cancer ◽  
Immune Cells ◽  
Cancer Metastasis ◽  
Diagnostic Value ◽  
Functional Enrichment ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Proposed Model ◽  
Tcga Dataset

Colorectal cancer (CRC) is a common malignant tumor and one of the leading causes of cancer-related deaths worldwide. CRC progression is greatly affected by the local microenvironment. In the study, we proposed a deep computational-based model for the classification of mRNA, lncRNA, and circRNA in exosomes. We, first, analyzed mRNA expression levels in CRC tumors and normal tissues. Secondly, we used GO and KEGG to analyze their functional enrichment. Thirdly, we analyzed the composition of immune cells in all TCGA samples and then evaluated the prognostic value of tumor-infiltrating immune cells in CRC. Lastly, we combined the TCGA dataset, i.e., COADN = 449 and ROADN = 6, for analysis and found that the expression levels of AKT3, LSM12, MEF2C, and RAB30 in exosomes were significantly correlated with tumor immune infiltration levels. The performance evaluation has shown that the proposed model based on neural networks performs better as compared to the existing methods. The proposed model can be used as a potential tool for the immune infiltration level and their role in cancer metastasis and progression, which can help us to explore potential strategies for CRC diagnosis, therapy, and prognosis.

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Poor Prognosis ◽  
Cancer Metastasis ◽  
Mrna Level ◽  
Normal Mucosa ◽  
Tnm Stage ◽  
Expression Levels ◽  
Normal Tissues

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

scholarly journals SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Hao Wang ◽  
Jinwen Yin ◽  
Yuntian Hong ◽  
Anli Ren ◽  
Haizhou Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cells ◽  
Macrophage Polarization ◽  
Clinical Stage ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Secretory Proteins ◽  
Advanced Clinical Stage ◽  
Multiple Tumor ◽  
Immune Infiltration

Colorectal cancer (CRC) is the second most lethal malignancy around the world. Limited efficacy of immunotherapy creates an urgent need for development of novel treatment targets. Secretogranin II (SCG2) is a member of the chromogranin family of acidic secretory proteins, has a role in tumor microenvironment (TME) of lung adenocarcinoma and bladder cancer. Besides, SCG2 is a stroma-related gene in CRC, its potential function in regulating tumor immune infiltration of CRC needs to be fully elucidated. In this study, we used western blot, real-time PCR, immunofluorescence and public databases to evaluate SCG2 expression levels and distribution. Survival analysis and functional enrichment analysis were performed. We examined TME and tumor infiltrating immune cells using ESTIMATE and CIBERSORT algorithm. The results showed that SCG2 expression was significantly decreased in CRC tumor tissues, and differentially distributed between tumor and adjacent normal tissues. SCG2 was an independent prognostic predictor in CRC. High expression of SCG2 correlated with poor survival and advanced clinical stage in CRC patients. SCG2 might regulate multiple tumor- and immune-related pathways in CRC, influence tumor immunity by regulating infiltration of immune cells and macrophage polarization in CRC.

scholarly journals Genomic Expression Profiling of Colorectal Cancer in Silico

2021 ◽  
Author(s):  
Feifei Liu ◽  
Yu Wang ◽  
Wenxue Li ◽  
Diancheng Li ◽  
Yuwei Xin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Analysis ◽  
Mrna Expression ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Analysis Tool ◽  
Hub Genes ◽  
Normal Tissues

Abstract Background: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system; the progression and prognosis of which are affected by a complicated network of genes and pathways. The aim of this study was to identify potential hub genes associated with the progression and prognosis of colorectal cancer (CRC).Methods: We obtained gene expression profiles from GEO database to search differentially expressed genes (DEGs) between CRC tissues and normal tissue. Subsequently, we conducted a functional enrichment analysis, generated a protein–protein interaction (PPI) network to identify the hub genes, and analyzed the expression validation of the hub genes. Kaplan–Meier plotter survival analysis tool was performed to evaluate the prognostic value of hub genes expression in CRC patients.Results: A total of 370 samples, involving CRC and normal tissues were enrolled in this article. 283 differentially expressed genes (DEGs), including 62 upregulated genes and 221 downregulated genes between CRC and normal tissues were selected. We finally filtered out 6 hub genes, including INSL5, MTIM, GCG, SPP1, HSD11B2, and MAOB. In the database of TCGA-COAD, the mRNA expression of INSL5, MT1M, HSD11B2, MAOB in tumor is lower than that in normal; the mRNA expression of SPP1 in tumor is higher than that in normal. In the HPA database, the expression of INSL5, GCG, HSD11B2, MAOB in tumor is lower than that in normal tissues; the expression of SPP1 in the tumor is higher than that in normal tissues. Survival analysis revealed that INSL5, GCG, SPP1 and MT1M may serve as prognostic biomarkers in CRC. Conclusions: We screened out six hub genes to predict the occurrence and prognosis of patients with CRC using bioinformatics methods, which may provide new targets and ideas for diagnosis, prognosis and individualized treatment for CRC.

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 Identification of Biomarkers Related to Immune Cell Infiltration in Hepatocellular Carcinoma Using Gene Co-Expression Network

2021 ◽  
Vol 27 ◽  
Author(s):  
Wanbang Zhou ◽  
Yiyang Chen ◽  
Ruixing Luo ◽  
Zifan Li ◽  
Guanwei Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Network Analysis ◽  
Tumor Progression ◽  
Protein Interactions ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Microenvironment ◽  
Hub Genes ◽  
Expression Levels ◽  
Immune Infiltration

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. Due to the lack of effective biomarkers and its complex immune microenvironment, the effects of current HCC therapies are not ideal. In this study, we used the GSE57957 microarray data from Gene Expression Omnibus database to construct a co-expression network. The weighted gene co-expression network analysis and CIBERSORT algorithm, which quantifies cellular composition of immune cells, were used to identify modules related to immune cells. Four hub genes (EFTUD2, GAPDH, NOP56, PA2G4) were identified by co-expression network and protein-protein interactions network analysis. We examined these genes in TCGA database, and found that the four hub genes were highly expressed in tumor tissues in multiple HCC groups, and the expression levels were significantly correlated with patient survival time, pathological stage and tumor progression. On the other hand, methylation analysis showed that the up-regulation of EFTUD2, GAPDH, NOP56 might be due to the hypomethylation status of their promoters. Next, we investigated the correlations between the expression levels of four hub genes and tumor immune infiltration using Tumor Immune Estimation Resource (TIMER). Gene set variation analysis suggested that the four hub genes were associated with numerous pathways that affect tumor progression or immune microenvironment. Overall, our results showed that the four hub genes were closely related to tumor prognosis, and may serve as targets for treatment and diagnosis of HCC. In addition, the associations between these genes and immune infiltration enhanced our understanding of tumor immune environment and provided new directions for the development of drugs and the monitoring of tumor immune status.

scholarly journals Circular RNA hsa_circ_0005046 and hsa_circ_0001791 May Become Diagnostic Biomarkers for Breast Cancer Early Detection

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Melika Ameli-Mojarad ◽  
Mandana Ameli-Mojarad ◽  
Mitra Nourbakhsh ◽  
Ehsan Nazemalhosseini-Mojarad
Keyword(s):  
Breast Cancer ◽  
Roc Curve ◽  
Expression Profiles ◽  
Circular Rna ◽  
Diagnostic Value ◽  
High Expression ◽  
Expression Level ◽  
Diagnostic Biomarker ◽  
Expression Levels ◽  
Normal Tissues

Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value ( P < 0.0001 ) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.

Prognostic and immune roles of synaptotagmin-4 in gastric cancer and brain lower-grade glioma

2020 ◽  
Author(s):  
Siyuan Jiang ◽  
Lizhe Zhu ◽  
Chao Jiang ◽  
Shibo Yu ◽  
Bin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Cells ◽  
Treg Cells ◽  
Lower Grade ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Lower Grade Glioma ◽  
Close Relationship ◽  
Human Protein Atlas ◽  
The Relationship

Abstract Background Synaptotagmins (SYTs) are a family of proteins whose primary function is serving as a calcium sensor in vesicle transport and exocytosis, playing an important role in the function of immune cells. There is also a close relationship between immune cells and tumours. SYT4 is one molecule involved in this relationship, but the relationship between SYT4 and cancer remains unclear. Therefore, we hypothesize that SYT4 can affect the prognosis of cancer, and may be related to immune cells. Methods The following databases were used to study the immunological and prognostic role of SYT4 in cancers: Oncomine, Kaplan-Meier plotter, The Human Protein Atlas, CCLE, GEPIA2, TIMER, and CGGA. Results SYT4 expressions were lower in many cancers than in normal tissues. Specifically in gastric cancer and lower-grade gliomas, SYT4 played a protective and harmful role, respectively. Moreover, a difference between SYT4 expression and the levels of immune infiltration existed in stomach adenocarcinoma (STAD) and brain lower-grade glioma (LGG). In addition, we found that the relationship between markers of monocytes, M1 and M2 macrophages, tumour-associated macrophages (TAMs), Treg cells, B lymphocytes, dendritic cells (DCs) and SYT4 expression was opposite in STAD and LGG. Conclusions The effect of SYT4 on the prognosis of patients with STAD and LGG was opposite. And SYT4 has different effects on immune infiltration in these two tumours. Therefore, SYT4 might be a potential prognostic and tumour immune-related biomarker in STAD and LGG.

Interferon Regulatory Factor 4 (IRF4) is a Prognostic Marker and Related to Immune Infiltration in Breast and Colorectal Cancers

2020 ◽  
Author(s):  
Qingyan Huang ◽  
Zhikang Yu ◽  
Yuhong Gan ◽  
Heming Wu ◽  
Zhixiong Zhong
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Enrichment Analysis ◽  
Interferon Regulatory Factor ◽  
Colorectal Cancers ◽  
Regulatory Factor ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Prognostic Outcome ◽  
Interferon Regulatory Factor 4

Abstract Background: Interferon regulatory factor 4 (IRF4) is a transcription factor that involves in immune cells differentiation. However, it is not clear the relationship between IRF4 and tumor prognosis and immune infiltration.Methods: IRF4 expression levels in different cancers and corresponding normal tissues were analyzed by Oncomine database and Tumor Immune Estimation Resource (TIMER). The prognosis value of IRF4 was assessed by PrognoScan and Kaplan-Meier plotter. The correlation between IRF4 and tumor-infiltrating immune cells and immune cells markers was performed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). In addition, we explored the genes regulated by IRF4 in Gene Transcription Regulation Database (GTRD) and then put the above genes in Enrich online tool for Gene Ontology (GO) and pathway enrichment analysis.Results: Decreased expression levels of IRF4 were observed in breast and colorectal cancers. Survival analysis shown that high level of IRF4 was associated with better prognostic outcome in breast and colorectal cancer patients. IRF4 expression was positively correlated with infiltrating levels of B cells, CD8+ T cells, T cells (general), dendritic cells (DCs), Th1, T cell exhaustion and monocytes, and immune cells markers. Beside, functional enrichment analysis of the potential genes regulated by IRF4 indicated that IRF4 may be involved in many important biological processes including immune regulation by regulating various genes.Conclusions: High expression of IRF4 shown better prognostic outcome for breast and colorectal cancers. IRF4 was associated with immune infiltration in breast and colorectal cancers. Therefore, IRF4 maybe serve as a potential prognostic biomarker in breast and colorectal cancers with immune infiltration.

scholarly journals Development of an Immune Infiltration-Related Eight-Gene Prognostic Signature in Colorectal Cancer Microenvironment

2020 ◽  
Vol 2020 ◽  
pp. 1-43
Author(s):  
Beilei Wu ◽  
Lijun Tao ◽  
Daqing Yang ◽  
Wei Li ◽  
Hongbo Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Immune Cells ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Roc Curves ◽  
Functional Enrichment ◽  
Cox Regression Analysis ◽  
Immune Genes ◽  
Score Model

Objective. Stromal cells and immune cells have important clinical significance in the microenvironment of colorectal cancer (CRC). This study is aimed at developing a CRC gene signature on the basis of stromal and immune scores. Methods. A cohort of CRC patients (n=433) were adopted from The Cancer Genome Atlas (TCGA) database. Stromal/immune scores were calculated by the ESTIMATE algorithm. Correlation between prognosis/clinical characteristics and stromal/immune scores was assessed. Differentially expressed stromal and immune genes were identified. Their potential functions were annotated by functional enrichment analysis. Cox regression analysis was used to develop an eight-gene risk score model. Its predictive efficacies for 3 years, 5 years, overall survival (OS), and progression-free survival interval (PFI) were evaluated using time-dependent receiver operating characteristic (ROC) curves. The correlation between the risk score and the infiltering levels of six immune cells was analyzed using TIMER. The risk score was validated using an independent dataset. Results. Immune score was in a significant association with prognosis and clinical characteristics of CRC. 736 upregulated and two downregulated stromal and immune genes were identified, which were mainly enriched into immune-related biological processes and pathways. An-eight gene prognostic risk score model was conducted, consisting of CCL22, CD36, CPA3, CPT1C, KCNE4, NFATC1, RASGRP2, and SLC2A3. High risk score indicated a poor prognosis of patients. The area under the ROC curves (AUC) s of the model for 3 years, 5 years, OS, and PFI were 0.71, 0.70, 0.73, and 0.66, respectively. Thus, the model possessed well performance for prediction of patients’ prognosis, which was confirmed by an external dataset. Moreover, the risk score was significantly correlated with immune cell infiltration. Conclusion. Our study conducted an immune-related prognostic risk score model, which could provide novel targets for immunotherapy of CRC.

Association of TGF-β expression with intratumoral infiltration of cytotoxic T lymphocytes in patients with microsatellite-stable colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3577-3577
Author(s):  
Amir Mehrvarz Sarshekeh ◽  
Riham Katkhuda ◽  
Anuj Verma ◽  
Shailesh M Advani ◽  
Michael J. Overman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Molecular Subtype ◽  
Rna Expression ◽  
Continuous Variables ◽  
Expression Levels

3577 Background: Transforming growth factor- β pathway (TGF-β) has an established role in promoting growth, invasion, metastasis as well as epithelial to mesenchymal (EMT) transition. Among 4 different described molecular subtypes of colorectal cancer (CRC), consensus molecular subtype 4 (CMS4) comprises up to 25% of CRC pts, distinguished by activation of this pathway, and is associated with higher relapse rate and poor prognosis. Recently, it has also been proposed that TGF-β activation drives immune evasion in murine models, but these findings have not been clinically validated. Methods: Using multi-gene RNA expression profiling, fresh-frozen paraffin-embedded samples of 35 patients with CRC were analyzed to determine TGF-β and EMT expression levels. Multiplexed IHC staining was performed on FFPE tumor blocks by using the Opal 7-Color fIHC Kit and the stained slides were scanned by a Vectra multispectral microscope (PerkinElmer) to measure infiltration of immune cells (i.e., T lymphocytes, cytotoxic T lymphocytes (CTL), T cell antigen-experienced, macrophages, etc.) in the tumor, stroma, and both components. TGF-β and EMT expression levels – as continuous variables - were compared with the infiltration of various immune cells using Spearman’s rank correlation analysis. Results: Among 35 pts, 28 pts had non-CMS1/MSS CRC. TGF-β RNA expression in the tumor microenvironment of these samples was inversely associated with the infiltration of CTL into the tumor (r=-0.43, p= 0.022). In contrast, there was no association of TGF-β with non-cytotoxic T-cells or macrophage infiltration. The tumor and stromal CTL infiltration differed substantially by CMS ( p=0.04, p=0.02, respectively) with tumor infiltration lowest in CMS4 (n=7). Consistent with this, EMT gene signature, which includes TGF-β expression, showed a similar inverse correlation with CTL infiltration (r=-0.48, p=0.009). Conclusions: TGF-β and EMT gene signatures have important roles in the exclusion of CTL in the tumor microenvironment of CRC pts. Inhibiting TGF-β pathway can potentially increase the intratumoral infiltration of CTL, which is a necessary (but not sufficient) step for immunotherapy response in MSS CRC. Clinical trials evaluating this hypothesis are currently ongoing (NCT03436563).

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