KIF23 Predict Immune Infiltration and Overall Survival in Gastric Cancer

Roc Curves ◽

Diagnostic Value ◽

Expression Level ◽

Immune Infiltration ◽

Abstract BackgroundKinesin family member 23 (KIF23), an index of tumor proliferation, can serve as a prognostic marker in numerous tumors. However, the relationship between KIF23 expression and immune infiltration and the diagnostic value of KIF23 remain unclear in GC (gastric cancer). This study aimed to explored the prognosis value of KIF23 and its interactions with tumor-infiltrating immune cells in GC by bioinformatics analysis. ResultsThe relationship between clinicopathologic features and KIF23 expression was also analyzed using the Wilcoxon rank-sum test and logistic regression. And the expression level of KIF23 was validated by IHC and GEO databases, which was consistent with informatics results. Receiver operating characteristic (ROC) curves were generated to evaluate the value of KIF23 as a binary classifier using the area under the curve (AUC value). High expression of KIF23 was significantly associated with longer overall survival and progression-free survival in GC. The mutations of KIF23 in GC were analyzed using cBioPortal and the Catalogue of Somatic Mutations in Cancer database. Enrichment analysis of co-expressed genes and KIF23 analysis was performed using LinkedOmics. By using STRING and GeneMANIA databases, we investigated the protein-coding genes related to KIF23 and its co-expression genes in GC tissues. Then, the relationship between KIF23 expression and immune infiltration in GC was investigated using Timer and GEPIA. We found that KIF23 might be used as a potential prognosis biomarker in GC. Subsequently, KIF23 expression level was correlated with the infiltration levels of CD8 + T cells, macrophages, neutrophils, and more obviously with B cells and dendritic cells. In addition, KIF23 expression was significantly associated with T cell exhaustion (CTLA-4 and GZMB). KIF23 expression showed correlations with the infiltration of diverse immune markers in GC. ConclusionOur findings suggest KIF23 can serve as a marker for immune infiltration and prognosis in GC.

Diagnostic Biomarker KIF23 is Associated With Immune Infiltration in Gastric Cancer

10.21203/rs.3.rs-778412/v1 ◽

2021 ◽

Author(s):

Maoshu Bai ◽

Xin Liu

Keyword(s):

Gastric Cancer ◽

Area Under The Curve ◽

Enrichment Analysis ◽

Roc Curves ◽

Diagnostic Value ◽

Expression Level ◽

Diagnostic Biomarker ◽

Immune Infiltration ◽

Abstract Background: Kinesin family member 23 (KIF23), an index of tumor proliferation, can serve as a prognostic marker in numerous tumors. However, the relationship between KIF23 expression and immune infiltration and the diagnostic value of KIF23 remain unclear in GC (gastric cancer). This study aimed to explored the diagnostic value of KIF23 and its interactions with tumor-infiltrating immune cells in GC by bioinformatics analysis. Mothods: The relationship between clinicopathologic features and KIF23 expression was also analyzed using the Wilcoxon rank-sum test and logistic regression. And the expression level of KIF23 was validated by IHC and GEO databases, which was consistent with informatics results. Receiver operating characteristic (ROC) curves were generated to evaluate the value of KIF23 as a binary classifier using the area under the curve (AUC value).Results: High expression of KIF23 was significantly associated with longer overall survival and progression-free survival in GC. The mutations of KIF23 in GC were analyzed using cBioPortal and the Catalogue of Somatic Mutations in Cancer database. Enrichment analysis of co-expressed genes and KIF23 analysis was performed using LinkedOmics. By using STRING and GeneMANIA databases, we investigated the protein-coding genes related to KIF23 and its co-expression genes in GC tissues. Then, the relationship between KIF23 expression and immune infiltration in GC was investigated using Timer and GEPIA. We found that KIF23 might be used as a potential diagnostic biomarker in GC. Subsequently, KIF23 expression level was correlated with the infiltration levels of CD8 + T cells, macrophages, neutrophils, and more obviously with B cells and dendritic cells. In addition, KIF23 expression was significantly associated with T cell exhaustion (CTLA-4 and GZMB). KIF23 expression showed correlations with the infiltration of diverse immune markers in GC. Conclusions: Our findings suggest KIF23 can serve as a marker for immune infiltration and diagnostic in GC, making it a potential treatment of target.

Significance of HMMR Overexpression in Hepatocellular Carcinoma

10.21203/rs.3.rs-1100876/v1 ◽

2022 ◽

Author(s):

Weidong Zhao ◽

Zhengxiang Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Progression ◽

Enrichment Analysis ◽

Expression Level ◽

Marker Genes ◽

Surface Binding ◽

Free Survival ◽

Immune Infiltration ◽

Abstract Background: Hyaluronan Mediated Motility Receptor (HMMR), as one of the key surface binding proteins of HA, is up-regulated in many tumors. What’s more, the expression level of HMMR is usually correlate with tumor progression and prognosis. However, the relationship between the expression of HMMR and the prognosis and immune infiltration of hepatocellular carcinoma (HCC) is still unclear.Methods: We analyzed the expression level of HMMR by TIMER database, GEO database and GEPIA database. The correlation between the HMMR expression and tumor prognosis was analyzed via the Kaplan-Meier plots. The TIMER database and GEPIA database were used to study the relationship between HMMR expression and immune infiltration. GO and KEGG enrichment analysis were used to explore the potential biological functions of HMMR.Results: HMMR expression was significantly higher in several human cancers, including HCC, than in corresponding normal tissues. High HMMR expression associated with poorer overall survival, disease-specific survival, progression-free survival and relapse-free survival in HCC patients. HMMR showed strong correlation with tumor-infiltrating B cells, CD4 + and CD8 + T cells, macrophages, neutrophils, and dendritic cells. Several immune marker genes expression, including CD86, IRF5, CD11b, KIRIDL4, CD11c, IFN-γ, STAT3, STAT5B, and CTLA4, have markedly positive correlations with HMMR expression. Enrichment analysis found that HMMR is mainly involved in cell cycle, DNA replication and repair, PLK1 pathway, E2F pathway, ATR pathway and AURORA B pathway.Conclusions: HMMR is a potential prognostic biomarker that influence tumor progression and correlated with tumor immune cells infiltration in HCC.

NPM1 Is a Prognostic Biomarker Involved in Immune Infiltration of Lung Adenocarcinoma and Associated With m6A Modification and Glycolysis

Frontiers in Immunology ◽

10.3389/fimmu.2021.724741 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xu-Sheng Liu ◽

Lu-Meng Zhou ◽

Ling-Ling Yuan ◽

Yan Gao ◽

Xue-Yan Kui ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Prognostic Biomarker ◽

Aerobic Glycolysis ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Expression Level ◽

Data Sets ◽

Translational Initiation ◽

Immune Infiltration ◽

BackgroundOverexpression of NPM1 can promote the growth and proliferation of various tumor cells. However, there are few studies on the comprehensive analysis of NPM1 in lung adenocarcinoma (LUAD).MethodsTCGA and GEO data sets were used to analyze the expression of NPM1 in LUAD and clinicopathological analysis. The GO/KEGG enrichment analysis of NPM1 co-expression and gene set enrichment analysis (GSEA) were performed using R software package. The relationship between NPM1 expression and LUAD immune infiltration was analyzed using TIMER, GEPIA database and TCGA data sets, and the relationship between NPM1 expression level and LUAD m6A modification and glycolysis was analyzed using TCGA and GEO data sets.ResultsNPM1 was overexpressed in a variety of tumors including LUAD, and the ROC curve showed that NPM1 had a certain accuracy in predicting the outcome of tumors and normal samples. The expression level of NPM1 in LUAD is significantly related to tumor stage and prognosis. The GO/KEGG enrichment analysis indicated that NPM1 was closely related to translational initiation, ribosome, structural constituent of ribosome, ribosome, Parkinson disease, and RNA transport. GSEA showed that the main enrichment pathway of NPM1-related differential genes was mainly related to mTORC1 mediated signaling, p53 hypoxia pathway, signaling by EGFR in cancer, antigen activates B cell receptor BCR leading to generation of second messengers, aerobic glycolysis and methylation pathways. The analysis of TIMER, GEPIA database and TCGA data sets showed that the expression level of NPM1 was negatively correlated with B cells and NK cells. The TCGA and GEO data sets analysis indicated that the NPM1 expression was significantly correlated with one m6A modifier related gene (YTHDF2) and five glycolysis related genes (ENO1, HK2, LDHA, LDHB and SLC2A1).ConclusionNPM1 is a prognostic biomarker involved in immune infiltration of LUAD and associated with m6A modification and glycolysis. NPM1 can be used as an effective target for diagnosis and treatment of LUAD.

ANXA9 as a novel prognostic biomarker associated with immune infiltrates in gastric cancer

PeerJ ◽

10.7717/peerj.12605 ◽

2021 ◽

Vol 9 ◽

pp. e12605

Author(s):

Tongtong Zhang ◽

Suyang Yu ◽

Shipeng Zhao

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Survival Curve ◽

Enrichment Analysis ◽

Prognostic Indicator ◽

Diagnostic Value ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Clinicopathological Parameters ◽

Background Gastric cancer (GC) is the most prevalent malignancy among the digestive system tumors. Increasing evidence has revealed that lower mRNA expression of ANXA9 is associated with a poor prognosis in colorectal cancer. However, the role of ANXA9 in GC remains largely unknown. Material and Methods The Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas databases were used to investigate the expression of ANXA9 in GC, which was then validated in the four Gene Expression Omnibus (GEO) datasets. The diagnostic value of ANXA9 for GC patients was demonstrated using a receiver operating characteristic (ROC) curve. The correlation between ANXA9 expression and clinicopathological parameters was analyzed in The Cancer Genome Atlas (TCGA) and UALCAN databases. The Kaplan-Meier (K-M) survival curve was used to elucidate the relationship between ANXA9 expression and the survival time of GC patients. We then performed a gene set enrichment analysis (GSEA) to explore the biological functions of ANXA9. The relationship of ANXA9 expression and cancer immune infiltrates was analyzed using the Tumor Immune Estimation Resource (TIMER). In addition, the potential mechanism of ANXA9 in GC was investigated by analyzing its related genes. Results ANXA9 was significantly up-regulated in GC tissues and showed obvious diagnostic value. The expression of ANXA9 was related to the age, gender, grade, TP53 mutation, and histological subtype of GC patients. We also found that ANXA9 expression was associated with immune-related biological function. ANXA9 expression was also correlated with the infiltration level of CD8+ T cells, neutrophils, and dendritic cells in GC. Additionally, copy number variation (VNV) of ANXA9 occurred in GC patients. Function enrichment analyses revealed that ANXA9 plays a role in the GC progression by interacting with its related genes. Conclusions Our results provide strong evidence of ANXA9 expression as a prognostic indicator related to immune responses in GC.

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

Disease Markers ◽

10.1155/2020/7347298 ◽

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 ◽

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.

A novel predictor of clinical progression in patients on active surveillance for prostate cancer

Canadian Urological Association Journal ◽

10.5489/cuaj.6122 ◽

2019 ◽

Vol 13 (8) ◽

Author(s):

Guan Hee Tan ◽

Antonio Finelli ◽

Ardalan Ahmad ◽

Marian Wettstein ◽

Alexandre Zlotta ◽

...

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Cox Regression ◽

Area Under The Curve ◽

Roc Curves ◽

Standard Of Care ◽

Low Risk ◽

Clinical Progression

Introduction: Active surveillance (AS) is standard of care in low-risk prostate cancer (PC). This study describes a novel total cancer location (TCLo) density metric and aims to determine its performance in predicting clinical progression (CP) and grade progression (GP). Methods: This was a retrospective study of patients on AS after confirmatory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx and <2 years follow-up. TCLo was the number of locations with positive cores at diagnosis (DBx) and CBx. TCLo density was TCLo / prostate volume (PV). CP was progression to any active treatment while GP occurred if Gleason ≥7 was identified on repeat biopsy or surgical pathology. Independent predictors of time to CP or GP were estimated with Cox regression. Kaplan-Meier analysis compared progression-free survival curves between TCLo density groups. Test characteristics of TCLo were explored with receiver operating characteristic (ROC) curves. Results: We included 181 patients who had CBx between 2012-2015, and met inclusion criteria. The mean age of patients was 62.58 years (SD=7.13) and median follow-up was 60.9 months (IQR=23.4). A high TCLo density score (>0.05) was independently associated with time to CP (HR 4.70, 95% CI: 2.62-8.42, p<0.001), and GP (HR 3.85, 95% CI: 1.91-7.73, p<0.001). ROC curves showed TCLo density has greater area under the curve than number of positive cores at CBx in predicting progression. Conclusion: TCLo density is able to stratify patients on AS for risk of CP and GP. With further validation, it could be added to the decision-making algorithm in AS for low-risk localized PC.

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 ◽

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.

Efficacy and Safety of FLOT regimen vs. DCF, FOLFOX, and ECF regimens as Perioperative Chemotherapy Treatments for Resectable Gastric Cancer Patients

10.1101/2021.01.26.21250550 ◽

2021 ◽

Author(s):

Pegah Farrokhi ◽

Alireza Sadeghi ◽

Mehran sharifi ◽

Payam Dadvand ◽

Rachel Riechelmann ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Cox Regression ◽

R0 Resection ◽

P Value ◽

Perioperative Chemotherapy ◽

Resectable Gastric Cancer ◽

Gastric Cancer Patients

AbstractAimThis study aimed to evaluate and compare the efficacy and toxicity of common regimens used as perioperative chemotherapy including ECF, DCF, FOLFOX, and FLOT to identify the most effective chemotherapy regimen with less toxicity.Material and MethodsThis retrospective cohort study was based on 152 eligible gastric cancer patients recruited in a tertiary oncology hospital in Isfahan, Iran (2014-2019). All resectable gastric cancer patients who had received one of the four chemotherapy regimens including ECF, DCF, FOLFOX, or FLOT, and followed for at least one year (up to five years) were included. The primary endpoint of this study was Overall Survival (OS), Progression-Free Survival (PFS), Overall Response Rate (ORR), and R0 resection. We also considered toxicity according to CTCAE (v.4.0) criteria as a secondary endpoint. Cox -regression models were used applied to estimate OS and PFS time, controlled for relevant covariates.ResultsOf included patients, 32(21%), 51(33.7%), 37(24.3%), and 32(21%) had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 25 months follow-up, overall survival was higher with the FLOT regimen in comparison with other regimens (hazard ratio [HR] = 0. 052). The median OS of the FLOT regimen was not reachable in Kaplan-Meier analysis and the median OS was 28, 26, and 23 months for DCF, FOLOFX, and ECF regimens, respectively. On the other hand, a median PFS of 25, 17, 15, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank = 0. 021). FLOT regimen showed 84. 4% ORR which was notably higher than other groups (p-value<0. 01).ConclusionsFor resectable gastric cancer patients, the perioperative FLOT regimen seemed to lead to a significant improvement in patients’ OS and PFS in comparison with ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered as the optimal option for managing resectable gastric cancer patients.

Immune Cell Landscape in Gastric Cancer

BioMed Research International ◽

10.1155/2021/1930706 ◽

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 ◽

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.

Overexpression of a novel oncogene Cadherin 6 correlates with tumor progression and poor prognosis in gastric cancer

10.21203/rs.3.rs-153934/v1 ◽

2021 ◽

Author(s):

Zongxian Zhao ◽

Shuliang Li ◽

Shilong Li ◽

Jun Wang ◽

Hai Lin ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Roc Curve ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

Expression Level ◽

Diagnostic Efficiency ◽

Gastric Tissue ◽

Diagnosis And Prognosis ◽

T Classification

Abstract BackgroundGastric cancer (GC) is one of the most common and fatal cancers worldwide and effective biomarkers aids in GC management and prognosis. Hence, we explored the role and function of cadherin 6 (CDH6) in diagnosis and prognosis of gastric cancer. MethodsThe expression level of CDH6 in GC tissue and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas dataset (TCGA). The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and expression of CDH6 were evaluated statistically and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. Forty-four GC tissues, corresponding adjacent normal tissues (n=20), and detailed clinical information were collected from Tianjin Medical University General Hospital, CDH6 expression level was detected for further validation. ResultsCDH6 was upregulated in GC samples compared with normal gastric tissue, and GSEA identified the citrate cycle tricarboxylic (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism oxidative phosphorylation, and pentose phosphate pathway as differentially enriched in GCs. According to the area under the ROC curve (AUC) (AUC=0.829 in TCGA and 0.966 in GSE54129), CDH6 had high diagnostic efficiency. Patients with high expression of CDH6 was associated with higher T classification and worse prognoses than those with low CDH6 expression in GC. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). ConclusionCDH6 was upregulated in GC and high CDH6 expression indicated higher T classification and worse prognoses. CDH6 could be a potentially independent molecular biomarker for diagnosis and prognosis of GC.