The relationship between HMGB1 and immune infiltration serves as a treatment target molecule in different cancer tissues: May be used therapeutic target for possible SARSCoV-2 infection

Background. To analyze the expression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and cognitive impairment, explore the relationship between the expression of VEGF family genes and prognosis of patients with HCC, and evaluate the predictive ability of VEGF in cognitive impairment using computerized methods. Methods. VEGF expression in liver cancer tissues and normal tissues was analyzed using bioinformatics methods. The Kaplan-Meier survival analysis method was also used to analyze the relationship between VEGF expression and the prognosis of patients with HCC. Furthermore, immune infiltration assessment and gene set enrichment analysis were performed. Meanwhile, the differential expression of VEGF family genes between patients with Alzheimer’s disease (AD) and healthy controls was also checked. Results. Based on The Cancer Genome Atlas (TCGA) database, the VEGF family genes (VEFGA, VEGFB, VEGFC, and VEGFD) were highly expressed in cancer tissues and were significantly associated with poor prognosis in HCC. In HCC, the VEGF family genes showed significant heterogeneity in their functional and immune infiltration characteristics. Finally, VEGF family genes were identified as prognostic biomarkers in AD and risk prediction markers in HCC. Conclusions. VEGF is highly expressed in patients with HCC and lowly expressed in patients with AD. VEGF has opposite opposing roles in the treatment of tumors and cognitive impairment.

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Gene Risk Signature of m6A Regulators, KIAA1429, YTHDF1, YTHDF2, METTL3 and Its Relationship with Immune Infiltration in Hepatocellular Carcinoma

10.21203/rs.3.rs-47948/v1 ◽

2020 ◽

Author(s):

Jingjing Guo ◽

Liwei Wang ◽

Hanfeng Xu ◽

Chuandong Zhu ◽

Jianning Wang ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Cox Regression ◽

Clinical Information ◽

High Risk Group ◽

Consensus Clustering ◽

Immune Infiltration ◽

Infiltrating Cells ◽

Cancer Tissues ◽

The Relationship

Abstract Background: Hepatocellular carcinoma (HCC) is a tumor of the digestive system with high mortality. N6-methyladenosine (m6A) is one of the most common forms of mRNA modification. Tumor neoantigens play an important role in anti-tumor immune response and predict the clinical response of immunotherapy. There are few studies on the relationship between m6A regulators and immune infiltrating cells. The objective of this study was to determine the gene expression and prognostic value of m6A regulators in hepatocellular carcinoma. Further, we explored the relationship between m6A regulators and immune-infiltrating cells.Methods: 13 m6A regulators expressions in 374 cancer tissues and 50 normal tissues were analyzed using RNA-seq data and clinical information in the TCGA database. Survival package was used to analyze the survival of patients in the two groups, and the corresponding clinical characteristics and gene expression were analyzed using univariate and multivariate Cox regression. We evaluated the expression of KIAA1429, YTHDF1, YTHDF2, and METTL3 in HCC and its correlation with TIICs using TIMER and CIBERSORT.Results: Most m6A regulators had higher expression levels in 374 cancer tissues. We confirmed two groups of HCC patients using a consensus clustering method. The prognosis of the cluster 1 group was poor compared with that of the cluster 2 group. The m6A regulators, KIAA1429, YTHDF1, YTHDF2, and METTL3 are highly expressed in the high-risk group of HCC. Furthermore, it was found that four m6A regulators (KIAA1429, YTHDF1, YTHDF2, and METTL3) are closely related to the clinicopathological characteristics and poor prognostic marker of hepatocellular carcinoma. We analyzed the correlation between KIAA1429, YTHDF1, YTHDF2, and METTL3 expression and the level of immune invasion of HCC.Conclusion: KIAA1429, YTHDF1, YTHDF2, and METTL3 as m6A regulators may regulate the tumor microenvironment through tumor immune infiltration cells to exert immune anti-tumor effects. KIAA1429, YTHDF1, YTHDF2, and METTL3 as molecular markers providing a new target for therapy of HCC in the further.

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CASC15：A tumor-associated long non-coding RNA

Current Pharmaceutical Design ◽

10.2174/1381612826666200922153701 ◽

2020 ◽

Vol 26 ◽

Author(s):

Bei Wang ◽

Wen Xu ◽

Yuxuan Cai ◽

Chong Guo ◽

Gang Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Therapeutic Target ◽

Cancer Colorectal ◽

Tumor Development ◽

Pathophysiological Mechanism ◽

Biological Processes ◽

Non Coding Rna ◽

Cancer Côlon ◽

The Relationship ◽

Long Non Coding Rna

Background: CASC15, one of long non-coding RNA, is involved in the regulation of many tumor biological processes, and is expected to become a new biological therapeutic target. This paper aims to elucidate the pathophysiological function of CASC15 in various tumors. Methods: The relationship between CASC15 and tumors was analyzed by searching references, and summarizes the specific pathophysiological mechanism of CASC15. Results: LncRNA CASC15 is closely related to tumor development, and has been shown to be abnormally high expressed in all kinds of tumors, including breast cancer, cervical cancer, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, colon cancer, colorectal cancer, cardiac hypertrophy, intrahepatic cholangiocarcinoma, leukemia, melanoma, tongue squamous cell carcinoma, nasopharyngeal carcinoma. However, CASC15 has been found to be downexpressed abnormally in ovarian cancer, glioma and neuroblastoma. Besides, it is identified that CASC15 can affect the proliferation, invasion and apoptosis of tumors. Conclusion: LncRNA CASC15 has the potential to become a new therapeutic target or marker for a variety of tumors.

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XIST: A Meaningful Long Noncoding RNA in NSCLC Process

Current Pharmaceutical Design ◽

10.2174/1381612826999201202102413 ◽

2020 ◽

Vol 26 ◽

Author(s):

Yujie Shen ◽

Yexiang Lin ◽

Kai Liu ◽

Jinlan Chen ◽

Juanjuan Zhong ◽

...

Keyword(s):

Therapeutic Target ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Critical Role ◽

Biological Functions ◽

Potential Therapeutic Target ◽

Considerable Evidence ◽

Lncrna Xist ◽

Nsclc Patients ◽

The Relationship

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.

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High Expression of PRMT6 Associated With Prognosis and Immune Infiltration in Glioma

10.21203/rs.3.rs-133309/v1 ◽

2020 ◽

Author(s):

Yi Yang ◽

Zhenshuang Wang ◽

Shengrong Long ◽

Jinhai Huang ◽

Chengran Xu ◽

...

Keyword(s):

Enrichment Analysis ◽

Clinical Work ◽

High Expression ◽

Clinical Indicators ◽

Immune Infiltration ◽

Tumor Tissues ◽

Potential Biomarker ◽

Patient Prognosis ◽

The Relationship

Abstract Background: Gliomas are characterised by easy invasion of surrounding tissues, high mortality and poor prognosis. Moreover, with the increase of grade, the prognosis of glioma is increasingly poor and not optimistic. Therefore, biological markers for glioma are needed in clinical work, which can be utilized to detect and evaluate the situation and prognosis of glioma patients. Many studies have found that the protein arginine methyltransferase 6 (PRMT6) expression is elevated in various tumors and is associated with patient prognosis. However, the role of PRMT6 in glioma has not been reported or analyzed. Methods: In this study, we used a variety of tumor related databases to analyze the mechanism of PRMT6 in tumors, especially gliomas, from the perspective of bioinformatics, and carried out relevant experimental verification with tumor tissues extracted from patients during surgery. In addition, we analyzed the relationship between PRMT6 expression and immune infiltration and immune-related cells, and discussed the possible mechanisms. We also discussed the role of PRMT6 expression in glioma from the perspectives of mutation, clinical indicators, enrichment analysis, and immunohistochemical results. Results: PRMT6 is significantly differentially expressed in a variety of tumors and is associated with survival and prognosis. Especially in gliomas, the expression of PRMT6 gradually increased with the increase of grade. In addition, PRMT6 can be used as an independent prognostic risk factor in the nomogram and has been verified in a variety of databases. Conclusions: Our results indicate that high expression of PRMT6 is a potential biomarker for predicting glioma prognosis and progression.

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Pan-Cancer Analysis of Prognostic and Immune Infiltrates for CXCs

Cancers ◽

10.3390/cancers13164153 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4153

Author(s):

Long Li ◽

Wenchao Yao ◽

Sen Yan ◽

Xianghui Dong ◽

Zhenyi Lv ◽

...

Keyword(s):

Animal Experiments ◽

Intestinal Flora ◽

Clinical Samples ◽

Mrna Levels ◽

Immune Infiltration ◽

Pancreatic Cancers ◽

Multiple Datasets ◽

Geo Dataset ◽

Cancer Tissues ◽

Pan Cancer

Background: CXCs are important genes that regulate inflammation and tumor metastasis. However, the expression level, prognosis value, and immune infiltration of CXCs in cancers are not clear. Methods: Multiple online datasets were used to analyze the expression, prognosis, and immune regulation of CXCs in this study. Network analysis of the Amadis database and GEO dataset was used to analyze the regulation of intestinal flora on the expression of CXCs. A mouse model was used to verify the fact that intestinal bacterial dysregulation can affect the expression of CXCs. Results: In the three cancers, multiple datasets verified the fact that the mRNA expression of this family was significantly different; the mRNA levels of CXCL3, 8, 9, 10, 14, and 17 were significantly correlated with the prognosis of three cancers. CXCs were correlated with six types of immuno-infiltrating cells in three cancers. Immunohistochemistry of clinical samples confirmed that the expression of CXCL8 and 10 was higher in three cancer tissues. Animal experiments have shown that intestinal flora dysregulation can affect CXCL8 and 10 expressions. Conclusion: Our results further elucidate the function of CXCs in cancers and provide new insights into the prognosis and immune infiltration of breast, colon, and pancreatic cancers, and they suggest that intestinal flora may influence disease progression through CXCs.

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Expression Level of Annexin A1 Contributes to the Evaluation of the Disease Progression and Treatment Effect of Lung Adenocarcinoma: A New Perspective from Retrospective Analysis

10.21203/rs.3.rs-401429/v1 ◽

2021 ◽

Author(s):

Biaoxue Rong ◽

Hongling Yan ◽

Ge Wu ◽

Kai Li ◽

Min Li ◽

...

Keyword(s):

Lung Cancer ◽

Lymph Node ◽

Disease Progression ◽

Treatment Effect ◽

Expression Level ◽

Annexin A1 ◽

Normal Tissues ◽

Node Metastasis ◽

Cancer Tissues ◽

The Relationship

Abstract Background: Increased Annexin A1 has been showed to be related to malignant biological characteristics of tumors; the aim of this study was to evaluate the relationship between the expression level of Annexin A1 and the disease progression and treatment effect of lung adenocarcinoma (LAC). Methods: The expression level of Annexin A1 in LAC tissues and cells was detected by the methods of immunohistochemistry, Real time-PCR and western blotting. The relationship between the expression of Annexin A1 and the disease progression and treatment effect of LAC was evaluated by descriptive statistics, T test and Chi-square test. Results: The protein expression of Annexin A1 was higher in lung cancer tissues and cells than that in normal tissues and 16 human bronchial epithelial (16HBE) cells (p<0.05). The level of Annexin A1 mRNA was higher in lung cancer tissues than that in normal tissues (p<0.05). The increase of Annexin A1 protein and mRNA was associated with the lymph node metastasis, advanced clinical stage (p<0.05). However, surgical resection and chemotherapy for LAC down-regulated the serum concentration of Annexin A1 in patients (p<0.05).Conclusions: Increased Annexin A1 protein and mRNA in LAC tissues correlate with the poor differentiation, lymph node metastasis and advanced stage of LAC. Surgical resection and chemotherapy for LAC down-regulate the serum concentration of Annexin A1 in patients. The results indicate that expression level of Annexin A1 contributes to the evaluation of the disease progression and treatment effect of LAC.

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Bioinformatic Analysis: The Role of LINC00634 in Colorectal Carcinoma

10.21203/rs.3.rs-801188/v1 ◽

2021 ◽

Author(s):

Fang Liu ◽

Fengyihuan Fu ◽

Yuqiang Nie

Keyword(s):

Esophageal Cancer ◽

Regression Analysis ◽

Prognostic Factors ◽

Colorectal Carcinoma ◽

Roc Curve ◽

Cox Regression ◽

Survival Outcomes ◽

Immune Infiltration ◽

The Relationship

Abstract Background: LINC00634 is highly expressed in esophageal cancer, and its depletion can suppress the viability and induce the apoptosis of esophageal cancer cells. However, there is a lack of studies that examine the relationship between LINC00634 expression and the clinicopathological features, survival outcomes, prognostic factors and tumor immune cell infiltration of colorectal carcinoma (CRC) patients.Objective: We aim at investigating the role of LINC00634 in colorectal carcinoma.Methods: We obtained data from the TCGA (The Cancer Genome Atlas) public database, GTEx (Genotype-Tissue Expression) database and clinical samples. Wilcoxon rank-sum test, Kruskal-Wallis test and logistic regression analysis were employed to assess the relationship between LINC00634 expression and the clinicopathological characteristics of CRC patients. Receiver operating characteristic (ROC) curve was constructed to evaluate the ability of LINC00634 for distinguishing between CRC patients and normal subjects based on the area under the curve (AUC) score. Univariate and multivariate analyses were conducted to evaluate the association between prognostic factors and survival outcomes. Kaplan-Meier curves and Cox regression analysis were employed to determine the contribution of LINC00634 expression to the prognosis of colorectal carcinoma patients. Immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were conducted to identify the significantly involved functions of LINC00634. Finally, a nomogram was constructed for internal verification based on the Cox regression data.Results: The expression of LINC00634 was upregulated in CRC patients, and markedly associated with N stage, residual tumor, pathological stage, and overall survival (OS) event. ROC curve showed that LINC00634 had strong diagnostic and prognostic abilities (AUC=0.74). The high expression of LINC00634 could predict poor disease specific survival (DSS; P=0.008) and poor overroll survival (OS;P<0.01). The expression of LINC00634 was independently associated with OS in CRC patients (P=0.019). GSEA and immune infiltration analysis demonstrated that LINC00634 expression was involved in gene transcription, epigenetic regulation and the functions of certain types of immune infiltrating cells. The c-index of the nomogram was 0.772 (95％CI: 0.744-0.799).Conclusions: Our study reveals that LINC00634 can serve as a potential prognostic biomarker for CRC patients.

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Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000491718 ◽

2018 ◽

Vol 48 (1) ◽

pp. 194-207 ◽

Cited By ~ 43

Author(s):

Juan Gu ◽

Yueping Wang ◽

Xuedong Wang ◽

Daoping Zhou ◽

Xinguo Wang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Tumour Size ◽

Luciferase Reporter ◽

Breast Cancer Cell Lines ◽

Human Breast ◽

Gene Assay ◽

Cancer Tissues ◽

The Relationship ◽

Lncrna Gas5

Background/Aims: An increasing body of evidence shows that long noncoding RNAs (lncRNAs) are involved in many different cancers. In this study, we aimed to investigate the competing endogenous RNA (ceRNA)-dependent mechanism by which the lncRNA GAS5 contributes to the development of breast cancer. Methods: A total of 68 breast cancer patients were enrolled, and breast cancer and adjacent normal tissues were collected. The human breast cancer cell lines MDA-MB-231, MDA-MB-453, BT549, SK-BR-3 and MCF-7 and human breast cell line MCF10A were utilized in this study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to detect expression of relative factors. RNA immunoprecipitation (RIP) was used to evaluate the relationship between GAS5 and miR-23a, and a dual luciferase reporter gene assay was employed to assess the relationship between ATG3 and miR-23a. A subcutaneous xenograft nude mouse model was generated to examine the role of GAS5 and its regulatory pathway in autophagy. Results: GAS5 levels were frequently decreased in breast cancer tissues and cell lines, and its relatively low expression was closely related to a larger tumour size, advanced tumour-node-metastasis (TNM) stage and estrogen receptor-negative (ER-) breast cancer tissues. More importantly, we found that GAS5 promoted autophagy, with enhanced autophagosome formation after GAS5 overexpression. GAS5 was found to act as a microRNA sponge in a pathway that included miR-23a and its target gene ATG3. The GAS5-miR-23a-ATG3 axis significantly regulated autophagy in vivo and in vitro. Conclusions: In summary, we report that the GAS5-miR-23a-ATG3 axis can be regarded as a key regulator of autophagy pathways in breast cancer; it may constitute a promising biomarker and therapeutic target in the future.

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

10.21203/rs.3.rs-21652/v2 ◽

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.

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