scholarly journals Novel Biomarker Genes for Prognosis of Survival and Treatment of Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaopeng Zhu ◽  
Sian Pan ◽  
Rui Li ◽  
Zebo Chen ◽  
Xingyun Xie ◽  
...  
Keyword(s):  
Immune Cell ◽  
Large Degree ◽  
Lower Grade ◽  
Central Nervous System Tumor ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Lower Grade Glioma ◽  
Tumor Mutational Burden ◽  
System Tumor ◽  
The Relationship

Glioblastoma multiforme (GBM) is the most aggressive malignant primary central nervous system tumor. Although surgery, radiotherapy, and chemotherapy treatments are available, the 5-year survival rate of GBM is only 5.8%. Therefore, it is imperative to find novel biomarker for the prognosis and treatment of GBM. In this study, a total of 141 differentially expressed genes (DEGs) in GBM were identified by analyzing the GSE12657, GSE90886, and GSE90598 datasets. After reducing the data dimensionality, Kaplan-Meier survival analysis indicated that expression of PTPRN and RIM-BP2 were downregulated in GBM tissues when compared with that of normal tissues and that the expression of these genes was a good prognostic biomarker for GBM (p<0.05). Then, the GSE46531 dataset and the Genomics of Drug Sensitivity in Cancer (GDSC) database were used to examine the relationship between sensitivity radiotherapy (RT) and chemotherapy for GBM and expression of PTPRN and RIM-BP2. The expression of PTPRN was significantly high in RT-resistant patients (p<0.05) but it was not related to temozolomide (TMZ) resistance. The expression level of RIM-BP2 was not associated with RT or TMZ treatment. Among the chemotherapeutic drugs, cisplatin and erlotinib had a significantly good treatment effect for glioma with expression of PTPRN or RIM-BP2 and in lower-grade glioma (LGG) with IDH mutation. (p < 0.05). The tumor mutational burden (TMB) score in the low PTPRN expression group was significantly higher than that in the high PTPRN expression group (p=0.013), with a large degree of tumor immune cell infiltration. In conclusion, these findings contributed to the discovery process of potential biomarkers and therapeutic targets for glioma patients.

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.

The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽  
2021 ◽  
Author(s):  
Peng Wang ◽  
Chen Luo ◽  
Peng-jie Hong ◽  
Wen-ting Rui ◽  
Shuai Wu
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Lower Grade ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Lower Grade Glioma ◽  
Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

scholarly journals Association Between Tumor Mutation Burden and Prognosis in Lower-Grade Glioma: An Exploratory Study 

2021 ◽  
Author(s):  
Di Cao ◽  
Jun Wang ◽  
Yan Lin ◽  
Guangwei Li
Keyword(s):  
Immune Cell ◽  
Differential Expression Analysis ◽  
Cell Infiltration ◽  
Lower Grade ◽  
Immune Cell Infiltration ◽  
Hub Genes ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Lower Grade Glioma ◽  
Genome Atlas

Abstract Background: The therapeutic efficacy of immune checkpoint inhibitor therapy is highly influenced by tumor mutation burden (TMB). The relationship between TMB and prognosis in lower-grade glioma is still unclear. We aimed to explore the relationships and mechanisms between them in lower-grade glioma.Methods: We leveraged somatic mutation data from The Cancer Genome Atlas (TCGA). Clinical cases were divided into high- and low-TMB groups based on the median of TMB. Infiltrating immune cells were analyzed using CIBERSORT and differential expression analysis between the prognostic groups performed. The key genes were identified as intersecting between immune-related genes. Cox regression and survival analysis were performed on the intersecting genes. A total of 7 hub genes were identified. The effect of somatic copy number alterations (SCNA) of the hub genes on immune cell infiltration was analyzed using TIMER, which was used to determine the risk factors and immune infiltration status in LGG. Subsequently, based on hub genes, a TMB Prognosis Index (TMBPI) model was constructed to predict the risk in LGG patients. Besides, this model was validated using data from TCGA and Chinese Glioma Genome Atlas (CGGA).Results: High-TMB favored worse prognosis (P＜0.001) and macrophage infiltration was an independent risk factor (P＜0.001). In the high-TMB group (P=0.033, P=0.009), the proportion of macrophages M0 and M2 increased and monocytes decreased (P=0.006). Besides, the SCNA of the hub genes affected the level of immune cell infiltration by varying degrees among which IGF2BP3, NPNT, and PLA2G2A had a significant impact. The AUC of the ROC curve at 1-, 3- and 5-years were all above 0.74.Conclusions: This study implies that high-TMB correlated with unfavorable prognosis in lower-grade glioma. And high-TMB may have an impact on prognosis by changing tumor microenvironment, caused by the SCNAs of genes. The TMBPI model accurately predicted prognosis in LGG patients.

scholarly journals CXC Chemokines as Therapeutic Targets and Prognostic Biomarkers in Skin Cutaneous Melanoma Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuezhi Zhou ◽  
Manjuan Peng ◽  
Ye He ◽  
Jingjie Peng ◽  
Xuan Zhang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Cutaneous Melanoma ◽  
Immune Cell ◽  
Gene Activation ◽  
Skin Tumor ◽  
Pathological Stage ◽  
Normal Tissues ◽  
The World ◽  
Cxc Chemokine ◽  
The Relationship

BackgroundSkin Cutaneous Melanoma (SKCM) is a tumor of the epidermal melanocytes induced by gene activation or mutation. It is the result of the interaction between genetic, constitutional, and environmental factors. SKCM is highly aggressive and is the most threatening skin tumor. The incidence of the disease is increasing year by year, and it is the main cause of death in skin tumors around the world. CXC chemokines in the tumor microenvironment can regulate the transport of immune cells and the activity of tumor cells, thus playing an anti-tumor immunological role and affecting the prognosis of patients. However, the expression level of CXC chemokine in SKCM and its effect on prognosis are still unclear.MethodOncomine, UALCAN, GEPIA, STRING, GeneMANIA, cBioPortal, TIMER, TRRUST, DAVID 6.8, and Metascape were applied in our research.ResultThe transcription of CXCL1, CXCL5, CXCL8, CXCL9, CXCL10, and CXCL13 in SKCM tissues were significantly higher than those in normal tissues. The pathological stage of SKCM patients is closely related to the expression of CXCL4, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13. The prognosis of SKCM patients with low transcription levels of CXCL4, CXCL9, CXCL10, CXCL11, and CXCL13 is better. The differential expression of CXC chemokines is mainly associated with inflammatory response, immune response, and cytokine mediated signaling pathways. Our data indicate that the key transcription factors of CXC chemokines are RELA, NF-κB1 and SP1. The targets of CXC chemokines are mainly LCK, LYN, SYK, MAPK2, MAPK12, and ART. The relationship between CXC chemokine expression and immune cell infiltration in SKCM was closed.ConclusionsOur research provides a basis for screening SKCM biomarkers, predicting prognosis, and choosing immunotherapy.

scholarly journals Immune Cell Landscape in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yang Yang ◽  
Wei He ◽  
Zi-rui Wang ◽  
Yu-jiao Wang ◽  
Lan-lan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
B Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Univariate Analysis ◽  
Molecular Therapy ◽  
Expression Level ◽  
Regulatory Factors ◽  
Normal Tissues ◽  
The Relationship

Background. The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. Methods. We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t -test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients’ clinical characteristics was assessed by univariate analysis. Results. In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients’ prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients’ gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. Conclusion. The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

scholarly journals GJA1 Expression and Its Prognostic Value in Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Silu Meng ◽  
Xinran Fan ◽  
Jianwei Zhang ◽  
Ran An ◽  
Shuang Li
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Logistic Regression ◽  
Gap Junction ◽  
Signaling Pathway ◽  
Immune Cells ◽  
Immune Cell ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Chi Squared

Gap Junction Protein Alpha 1 (GJA1) belongs to the gap junction family and has been widely studied in cancers. We evaluated the role of GJA1 in cervical cancer (CC) using public data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. The difference of GJA1 expression level between CC and normal tissues was analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA), six GEO datasets, and the Human Protein Atlas (HPA). The relationship between clinicopathological features and GJA1 expression was analyzed by the chi-squared test and the logistic regression. Kaplan–Meier survival analysis and Cox proportional hazard regression analysis were used to assessing the effect of GJA1 expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways regulated by GJA1. Immune Cell Abundance Identifier (ImmuCellAI) was chosen to analyze the immune cells affected by GJA1. The expression of GJA1 in CC was significantly lower than that in normal tissues based on the GEPIA, GEO datasets, and HPA. Both the chi-squared test and the logistic regression showed that high-GJA1 expression was significantly correlated with keratinization, hormone use, tumor size, and FIGO stage. The Kaplan–Meier curves suggested that high-GJA1 expression could indicate poor prognosis ( p = 0.0058 ). Multivariate analysis showed that high-GJA1 expression was an independent predictor of poor overall survival (HR, 4.084; 95% CI, 1.354-12.320; p = 0.013 ). GSEA showed many cancer-related pathways, such as the p53 signaling pathway and the Wnt signaling pathway, were enriched in the high-GJA1-expression group. Immune cell abundance analysis revealed that the abundance of CD8 naive, DC, and neutrophil was significantly increased in the high-GJA1-expression group. In conclusion, GJA1 can be regarded as a potential prognostic marker of poor survival and therapeutic target in CC. Moreover, many cancer-related pathways may be the critical pathways regulated by GJA1. Furthermore, GJA1 can affect the abundance of immune cells.

scholarly journals Prognosis and immune function of Synaptotagmin-4 in gastric cancer and brain low-grade glioma

2020 ◽  
Author(s):  
Siyuan Jiang ◽  
Lizhe Zhu ◽  
Chao Jiang ◽  
Shibo Yu ◽  
Bin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Function ◽  
Treg Cells ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Lower Grade ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Kaplan Meier

Abstract Background Synaptotagmins (SYTs) are a family of proteins whose primary feature is the calcium sensor in vesicle transport and exocytosis. SYT4 is one of them, but the relationship between SYT4 and cancer remains unclear. We aim to explore the prognosis and immune function of SYT4 in gastric cancer and low-grade glioma. Methods These databases were used to study the immunological and prognostic role of SYT4 in cancers, including the Oncomine database, Kaplan-Meier plotter, GEPIA2, TIMER, and CGGA. Results The study suggested that the expression levels of SYT4 were lower in both gastric cancer and glioma, compared to the normal tissues. And SYT4 played a protective and harmful role in low-grade gliomas and gastric cancer, respectively. Moreover, we found that a difference between SYT4 expression and the levels of immune infiltration in stomach adenocarcinoma (STAD) and brain lower-grade glioma (LGG). Besides, after exploring the association between the expression levels of SYT4 and markers of immune cells in these two cancers, we found that markers of monocytes, M1/ M2, tumor-associated macrophages (TAMs), Treg cells and SYT4 expressions had an opposite correlation in STAD and LGG. Conclusions SYT4 had an effect on the prognosis of gastric cancer and glioma patients and was related to immune infiltration by regulating TAMs and Treg cells. SYT4 can be used as a prognostic biomarker for STAD and LGG.

scholarly journals Low Expression of KAT6B May Affect Prognosis in Hepatocellular Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Junjie Jiang ◽  
Hui-Ju Wang ◽  
Xiao-Zhou Mou ◽  
Huanqing Zhang ◽  
YiZhen Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
Clinicopathological Parameters ◽  
Expression Array ◽  
Chi Square ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
The Relationship ◽  
Liver Tissues

Aims: Lysine acetyltransferase 6B (KAT6B), is a histone acetyltransferase implicated to have a role in tumor suppression. However, the relationship between KAT6B and hepatocellular carcinoma (HCC) is unclear. The purpose of this study was to detect the expression of KAT6B in HCC tissues and analyze its connection with the clinicopathological features of HCC. Methods: First, we performed immunohistochemical staining on 250 HCC tissues and 222 non-tumor liver tissues to examine the expression of KAT6B.Then the relation between KAT6B expression and clinicopathological parameters was analyzed by chi-square test, and the overall survival analysis was conducted by Kaplan-Meier survival method. In addition, based on the Oncomine expression array online and the UALCAN database, we compared KAT6B expression differences between normal liver tissues and HCC tissues more broadly. Results: Compared with normal tissues, KAT6B expression was significantly lower in HCC tissues. Low KAT6B expression was found to be related to gender, AFP level, and tumor size. According to the online database, KAT6B expression was found to be decreased in HCC tissues and high in normal tissues. Conclusions: Lower expression of KAT6B is associated with poor prognosis of HCC, and KAT6B may be a potential tumor suppressor in liver cancer.

scholarly journals Bromine domain protein 4 is an important marker for prognosis of ovarian cancer and tumor immune infiltration

2021 ◽  
Author(s):  
Chujia Chen ◽  
Zhiyong Yang ◽  
Qiuchan Zhao ◽  
Bangming Xu ◽  
Donglin Cao
Keyword(s):  
Ovarian Cancer ◽  
Immune Cell ◽  
Expression Level ◽  
Immune Markers ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Domain Protein ◽  
Kaplan Meier Plotter

Abstract Background Ovarian cancer (OC) is one of the most common malignant gynecological tumors, but its pathogenesis is unclear. Bromine domain protein 4 (BRD4) is involved in the malignant transformation of cells, as well as the invasion and metastasis of tumor cells. The biological role of BRD4 in ovarian cancer is yet to be determined. Methods The differential expression of BRD4 in OC and corresponding normal tissues was evaluated by exploring the Tumor Immune Assessment Resources (TIMER) and the Oncomine database. The correlation between the expression level of BRD4 and the prognosis of OC patients was evaluated using the Kaplan-Meier Plotter database. Using TIMER, we further studied the correlation between BRD4 and tumor immune cell infiltration. Results The expression of BRD4 was significantly higher in patients with OC, and high BRD4 expression was closely related to low overall survival rate. The BRD4 expression was associated with the levels of immune markers of macrophages, dendritic cells, neutrophils, and various effector T cells. Taken together, these findings show that BRD4 expression is significantly related to immune infiltration in OC and suggest that BRD4 might play an important role in the immune evasion of OC cells. Conclusion The expression level of BRD4 in OC tissues is significantly upregulated, and its high expression is significantly associated with poor prognosis of patients and is closely related to tumor immune infiltration. These results suggest that BRD4 can be used as a prognostic marker and a marker of immune infiltration in OC.

scholarly journals Downregulated Expression of linc-ROR in Gastric Cancer and Its Potential Diagnostic and Prognosis Value

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Xiuchong Yu ◽  
Haixiang Ding ◽  
Yijiu Shi ◽  
Liangwei Yang ◽  
Jiaming Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Polymerase Chain ◽  
Long Intergenic Noncoding Rna ◽  
Clinical Potential ◽  
The Relationship

Background. Gastric cancer (GC) is one of the global mortality diseases and has a poor prognosis due to the lack of ideal tumor biomarkers. Numerous studies have shown that long noncoding RNAs (lncRNAs) can affect the occurrence and development of cancer through a variety of signaling pathways. The abnormal expression and specificity of lncRNAs in tumors make them potential biomarkers of cancers. Nevertheless, the diagnostic roles of lncRNAs in GC have been poorly understood. So this study focuses on the clinical diagnostic value of lncRNAs in GC. Materials and Methods. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to investigate the expression of the linc-ROR (long intergenic noncoding RNA, regulator of reprogramming) in 105 paired GC tissues and adjacent normal tissues. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were established to assess the diagnostic value of linc-ROR. The relationship between expression of linc-ROR and clinicopathological factors of patients with GC was further explored. Kaplan-Meier analysis was performed to evaluate the prognostic value of linc-ROR expression. Results. The linc-ROR expression level was significantly decreased in GC tissues compared with its adjacent nontumor tissues ( n = 105 , P < 0.001 ). We also discovered that linc-ROR was evidently downregulated in 68.6% (72/105) of GC tissues. The AUC’s value of linc-ROR was up to 0.6495, with sensitivity and specificity of 0.7524 and 0.5143, respectively. Intriguingly, the linc-ROR expression levels were obviously associated with tumor differentiation ( P = 0.004 ). Notably, the overall survival rate of GC patients with high expression of linc-ROR was significantly higher than those with low expression. Conclusion. Our data revealed that linc-ROR has clinical potential as a biomarker for the diagnosis of GC and assessment of its prognosis.

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