UGT1A Gene Family Members Serve as Potential Targets and Prognostic Biomarkers for Pancreatic Cancer

Background. Pancreatic cancer (PC) is one of the most common cancers worldwide, with high mortality. The UGT1A gene family plays important roles in pharmacology and toxicology, contributing to interindividual differences in drug disposition. However, mRNA expression and prognostic value of the UGT1A gene family in PC have not been identified. Methods. Oncomine, GEPIA2, DAVID 6.8, Metascape, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TRRUST v2, TIMER, and R software were used in our study. Results. The transcriptional levels of UGT1A1/3/6/8/9/10 in PC tissues were significantly higher than those in normal tissues. These results were further validated using five pairs of PC tumor tissues and adjacent nontumor tissues. A significant correlation was found between the expression of UGT1A1/6/10 and the pathological stage of PC. PC patients with lower transcriptional levels of UGT1A1/4/5/6/10 were associated with a better prognosis. The differentially expressed UGT1A gene family functions were primarily related to the glucuronidation pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that HNF1A, AHR, and CDX2 are key transcription factors for the UGT1A gene family. Furthermore, the expression levels of UGT1A1/3/8/9/10 were positively correlated with the activities of tumor-infiltrating immune cells, especially B cells. The expression levels of UGT1A6/9 were negatively correlated with macrophage infiltration levels. Conclusions. These results suggest that the UGT1A gene family could serve as a potential prognostic biomarker and target for PC. However, future studies are required to validate our findings and promote the clinical utility of the UGT1A gene family in PC.

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COL5A3 is a prognostic biomarker and correlated with immune infiltrates in pancreatic cancer

10.21203/rs.3.rs-889396/v1 ◽

2021 ◽

Author(s):

Yongjie Li ◽

Min Zeng ◽

Ting Wang ◽

Feng Jiang

Keyword(s):

Pancreatic Cancer ◽

Roc Curve ◽

Prognostic Biomarker ◽

Expression Profiles ◽

Functional Enrichment ◽

High Expression ◽

Immune Infiltration ◽

Normal Tissues ◽

Kaplan Meier ◽

Tumor Tissues

Abstract Background Pancreatic cancer is a malignant tumor of digestive system with high fatality rate, and its prognosis is very poor. Type Ⅴ collagen α3 (COL5A3) is highly expressed in a variety of tumor tissues, but its prognostic value and immune infiltration in pancreatic cancer are still unclear. Therefore, we evaluated the prognostic role of COL5A3 in pancreatic cancer and its correlation with immune infiltration. Methods The transcriptional expression profiles of COL5A3 in pancreatic cancer and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). In the GEO (Gene expression omnibus) dataset (GSE16515), we compared the expression of COL5A3 in normal and tumor tissues. The expression of COL5A3 protein was evaluated by the human protein atlas (THPA). The effect of COL5A3 on survival was evaluated by Kaplan-Meier method. Receiver operating characteristic (ROC) curve was used to distinguish pancreatic cancer from paracancerous normal tissues. Protein-protein interaction (PPI) network was constructed by the STRING. Use the "ClusterProfiler" package for functional enrichment analysis. Tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB) were used to determine the relationship between COL5A3mRNA expression and immune infiltration. Results Compared with normal tissues, COL5A3 is highly expressed in pancreatic cancer tissues. The high expression of COL5A3 is related to the poor clinicopathological features and poor prognosis of pancreatic cancer. Kaplan-Meier survival analysis showed that the prognosis of pancreatic cancer patients with high expression of COL5A3 was worse than that of patients with low expression of COL5A3. ROC curve shows that COL5A3 has high sensitivity and specificity in the diagnosis of pancreatic cancer. Correlation analysis showed that the expression of COL5A3mRNA was related to immune cell infiltration. Conclusion This study reveals for the first time that COL5A3 may be a new prognostic biomarker related to immune infiltration and provide a new target for the diagnosis and treatment of pancreatic cancer.

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High Expression of AMIGO2 Is an Independent Predictor of Poor Prognosis in Pancreatic Cancer

10.21203/rs.3.rs-557347/v1 ◽

2021 ◽

Author(s):

zhang jing ◽

Fu xi feng

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Tp53 Mutation ◽

Enrichment Analysis ◽

High Expression ◽

Normal Tissues ◽

Kaplan Meier ◽

Human Protein Atlas ◽

Cancer Tissues ◽

Kaplan Meier Plotter

Abstract Background.The AMIGO2 extracellular domain has a leucine - rich repetitive domain (LRR) and encodes a type 1 transmembrane protein , and is a member of the AMIGO gene family .Although the abnormal expression of AMIGO2 is associated with multiple tumors , the relationship with pancreatic cancer is not clear .Methods.The expression of AMIGO2 mRNA and proteins in pancreatic cancer was analyzed using NCBI GEO database and GEPIA2、Human Protein Atlas database.The RNA sequencing data of pancreatic cancer and clinical data of pancreatic cancer patients in TCGA public database were retrospectively analyzed. AMIGO2 gene expression data and their corresponding clinical information in the sample were analyzed retrospectively. The diagnostic value of AMIGO2 expression in pancreatic cancer patients was determined by receiver operating characteristic (ROC) curve analysis. The effects of AMIGO2 expression differences on survival time of pancreatic cancer patients were analyzed by Kaplan-Meier Plotter database and GEPIA2 database.The correlation between AMIGO2 gene and TP53 mutation in pancreatic cancer was analyzed by UALCAN database and TIMER database. The similar genes of AMIGO2 in pancreatic cancer were analyzed by GEPIA2 database, and the biological behavior, cellular composition, molecular function enrichment analysis and protein interaction of similar genes were analyzed by DAVID database and Metascape database. enrichment analysis of AMIGO2 similar gene pathways using KEGG database. The MSIGDB cancer coexpression module in Harmonizome database and TIMER database were used to study the gene coexpression of AMIGO2 in pancreatic cancer. AMIGO2 transcription factors were predicted using the JASPER database. The pathway of AMIGO2 transcription factors and co-expression genes was studied by KEGG database.Results. The expression of AMIGO2 (GSE16515, GSE15471) in pancreatic cancer tissues was significantly higher than that in normal tissues (P < 0.05). The GEPIA2 database also confirmed that the expression of AMIGO2 in pancreatic cancer tissues was significantly higher than that in normal tissues. The expression level of AMIGO2 gene was correlated with lymph node metastasis and histological grade of pancreatic cancer (P<0.05). The high expression of AMIGO2 protein in pancreatic cancer was confirmed in Human Protein Atlas database. The overall survival rate and progression-free survival rate of pancreatic cancer patients with high expression of AMIGO2 were significantly shorter than those of patients with low expression of AMIGO2 in Kaplan-Meier Plotter database and GEPIA2 database. In the gene ontology analysis, it is found that AMIGO2 is involved in cell adhesion, proliferation, migration, apoptosis and other biological processes. KEGG analysis pathway is concentrated in the focal adhesion pathway, mitotic cell cycle changes, and the regulation of cell protein localization. Abnormal expression of AMIGO2 was found in pancreatic cancer caused by TP53 mutation in UALCAN and TIMER databases.In JASPAR database, we predicted that there are 10 transcription sites between AMIGO2 and transcription factor MYB. In addition, there are positive genes related to AMIGO2 in TIMER database and transcription factor MYB regulates tumor cell proliferation and apoptosis in PI3K-Akt signal transduction pathway and WNT signal pathway in pancreatic cancer.

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Expression patterns and prognostic values of the cyclin-dependent kinase 1 and cyclin A2 gene cluster in pancreatic adenocarcinoma

Journal of International Medical Research ◽

10.1177/0300060520930113 ◽

2020 ◽

Vol 48 (12) ◽

pp. 030006052093011

Author(s):

Peng Jiang ◽

Ming Zhang ◽

Liangliang Gui ◽

Kai Zhang

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Adenocarcinoma ◽

Malignant Tumors ◽

Expression Patterns ◽

Advanced Tumor Stage ◽

Tissue Samples ◽

Expression Levels ◽

Kaplan Meier ◽

Advanced Tumor ◽

Kaplan Meier Plotter

Objective Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignant tumors worldwide. Various studies based on cell lines, preclinical mouse models, and human tissue samples have shown that cell cycle-associated proteins are involved in the tumorigenesis and progression of PAAD. Methods Herein, we analyzed the relationships between CDK1 and CCNA2 gene expression and prognosis in patients with pancreatic cancer, using information from the Oncomine, cBioportal, Kaplan–Meier Plotter, and GEPIA databases. Results Expression levels of CDK1 and CCNA2 were significantly higher in PAAD compared with control tissues, and were associated with more advanced tumor stage. Survival analyses using the Kaplan–Meier Plotter database further confirmed that increased expression levels of CDK1 and CCNA2 were associated with a poor prognosis in patients with pancreatic cancer. Conclusions The results of this study suggest that CDK1 and CCNA2 may be potential therapeutic targets and prognostic biomarkers in patients with PAAD.

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Identification of ATFs in Human Breast Cancer by Integrated Bioinformatic Analysis

10.21203/rs.3.rs-948401/v1 ◽

2021 ◽

Author(s):

chenchen Geng ◽

Qian Pu ◽

Shuxu Tian ◽

Wenwen Geng ◽

Haiyan Wang ◽

...

Keyword(s):

Breast Cancer ◽

Bioinformatic Analysis ◽

Free Survival ◽

Expression Levels ◽

Normal Tissues ◽

Kaplan Meier ◽

Protein Expressions ◽

Human Protein Atlas ◽

Activating Transcription Factor ◽

Kaplan Meier Plotter

Abstract Background: To obtain a thorough comprehension of the profile and prognosis of activating transcription factor (ATF) family members in breast cancer.Method: We searched Oncomine, GEPIA, cBioPortal, Kaplan-Meier plotter, and CancerSEA databases to assess expression level, prognostic value, and functions of ATFs in breast cancer. Results: In breast cancer, we found that the expression levels of genes like ATF1, ATF5, and ATF6, were higher than in normal tissues. While the expression levels of ATF3, ATF4, ATF7 were lower in the former than in the latter. Similarly, the ATFs protein expressions were consistent with this in the Human Protein Atlas database. High expressions of ATF2, ATF4, and ATF6-7 were associated with good relapse-free survival. Increased expressions of ATF4 and ATF7 had high overall survival. Conversely, the mRNA expression of ATF1 was negatively correlated with distant metastasis-free survival. Similarly, high expression of ATF2 had reduced post-progression survival. Conclusions: ATF1 was a target of potential therapeutic interest for breast cancer, and ATF4 and ATF6-7 were potential prognostic factors in evaluating breast cancer.

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COL5A3 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Pancreatic Cancer

10.21203/rs.3.rs-889396/v2 ◽

2021 ◽

Author(s):

Yongjie Li ◽

Min Zeng ◽

Ting Wang ◽

Feng Jiang

Keyword(s):

Pancreatic Cancer ◽

Roc Curve ◽

Prognostic Biomarker ◽

Expression Profiles ◽

Functional Enrichment ◽

High Expression ◽

Immune Infiltration ◽

Normal Tissues ◽

Kaplan Meier ◽

Tumor Tissues

Abstract Pancreatic cancer is a malignant tumor of digestive system with high fatality rate, and its prognosis is very poor. Type Ⅴ collagen α3 (COL5A3) is highly expressed in a variety of tumor tissues, but its prognostic value and immune infiltration in pancreatic cancer are still unclear. Therefore, we evaluated the prognostic role of COL5A3 in pancreatic cancer and its correlation with immune infiltration. The transcriptional expression profiles of COL5A3 in pancreatic cancer and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). In the GEO (Gene expression omnibus) dataset (GSE16515), we compared the expression of COL5A3 in normal and tumor tissues. The expression of COL5A3 protein was evaluated by the human protein atlas (THPA). The effect of COL5A3 on survival was evaluated by Kaplan-Meier method. Receiver operating characteristic (ROC) curve was used to distinguish pancreatic cancer from paracancerous normal tissues. Protein-protein interaction (PPI) network was constructed by the STRING. Use the "ClusterProfiler" package for functional enrichment analysis. Tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB) were used to determine the relationship between COL5A3 mRNA expression and immune infiltration. Compared with normal tissues, COL5A3 is highly expressed in pancreatic cancer tissues. The high expression of COL5A3 is related to the poor clinicopathological features and poor prognosis of pancreatic cancer. Kaplan-Meier survival analysis showed that the prognosis of pancreatic cancer patients with high expression of COL5A3 was worse than that of patients with low expression of COL5A3. ROC curve shows that COL5A3 has high sensitivity and specificity in the diagnosis of pancreatic cancer. Correlation analysis showed that the expression of COL5A3 mRNA was related to immune cell infiltration. This study reveals for the first time that COL5A3 may be a new prognostic biomarker related to immune infiltration and provide a new target for the diagnosis and treatment of pancreatic cancer.

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Identification of Flap Endonuclease 1 With Diagnostic and Prognostic Value in Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.603114 ◽

2021 ◽

Vol 11 ◽

Author(s):

Min Wu ◽

Pan Zhang ◽

Penghui Wang ◽

Zhen Fang ◽

Yaqin Zhu

Keyword(s):

Breast Cancer ◽

Prognostic Marker ◽

Prognostic Value ◽

Diagnostic Value ◽

Roc Curve Analysis ◽

Free Survival ◽

Flap Endonuclease 1 ◽

Normal Tissues ◽

Kaplan Meier ◽

Kaplan Meier Plotter

ObjectiveThis study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC).MethodsELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value.ResultsBioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values>0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients.ConclusionFEN1 might be a novel diagnostic and prognostic marker for BC.

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DPYSL2 as potential diagnostic and prognostic biomarker linked to immune infiltration in lung adenocarcinoma

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02379-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yang-Jie Wu ◽

Ai-Tao Nai ◽

Gui-Cheng He ◽

Fei Xiao ◽

Zhi-Min Li ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Roc Curve ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

List Type ◽

Gene Set Enrichment ◽

Gene Set ◽

Normal Tissues ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract Background Dihydropyrimidinase like 2 (DPYSL2) has been linked to tumor metastasis. However, the function of DPSY2L in lung adenocarcinoma (LUAD) is yet to be explored. Methods Herein, we assessed DPYSL2 expression in various tumor types via online databases such as Oncomine and Tumor Immune Estimation Resource (TIMER). Further, we verified the low protein and mRNA expressions of DPYSL2 in LUAD via the ULCAN, The TCGA and GEPIA databases. We applied the ROC curve to examine the role of DPYSL2 in diagnosis. The prognostic significance of DPYSL2 was established through the Kaplan–Meier plotter and the Cox analyses (univariate and multivariate). TIMER was used to explore DPYSL2 expression and its connection to immune infiltrated cells. Through Gene Set Enrichment Analysis, the possible mechanism of DPYSL2 in LUAD was investigated. Results In this study, database analysis revealed lower DPYSL2 expression in LUAD than in normal tissues. The ROC curve suggested that expression of DPYSL2 had high diagnostic efficiency in LUAD. The DPYSL2 expression had an association with the survival time of LUAD patients in the Kaplan–Meier plotter and the Cox analyses. The results from TIMER depicted a markedly positive correlation of DPYSL2 expression with immune cells infiltrated in LUAD, such as macrophages, dendritic cells, CD4+ T cells, and neutrophils. Additionally, many gene markers for the immune system had similar positive correlations in the TIMER analysis. In Gene Set Enrichment Analysis, six immune-related signaling pathways were associated with DPYSL2. Conclusions In summary, DPYSL2 is a novel biomarker with diagnostic and prognostic potential for LUAD as well as an immunotherapy target. Highlights Expression of DPYSL2 was considerably lower in LUAD than in normal tissues. Investigation of multiple databases showed a high diagnostic value of DPYSL2 in LUAD. DPYSL2 can independently predict the LUAD outcomes. Immune-related mechanisms may be potential ways for DPYSL2 to play a role in LUAD.

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NaPi- II b as a potential diagnostic and prognostic biomarker in ovarian cancers

10.1101/394759 ◽

2018 ◽

Author(s):

Shoufeng Zhao ◽

Zhipeng Wang

Keyword(s):

Ovarian Cancer ◽

Cancer Cell Line ◽

Normal Tissues ◽

Diagnosis And Prognosis ◽

Kaplan Meier ◽

Potential Biomarker ◽

Tumor Types ◽

First Time ◽

Kaplan Meier Plotter ◽

Normal Controls

ABSTRACTOvarian cancer (OC) is commonly diagnosed at an advanced stage due to a lack of effective biomarkers and specificity required for accurate clinical diagnosis. The purpose of this study was to estimate the diagnosis and prognosis of the NaPi- II b in ovarian cancer. Herein, by performing data mining using the databases of Oncomine and Cancer Cell Line Encyclopedia (CCLE), we are for the first time to report that the expression level of NaPi- II b transcripts in a variety of tumor types compared with the normal controls. Based on Kaplan-Meier plotter, we investigated the prognostic values of NaPi- II b specifically high expressed in OC patients. The results of the Oncomine analysis showed that relative expression of NaPi- II b was distinctly high in OC tissues vs. normal tissues. CCLE analysis indicated that the expression of NaPi- II b in OC cell lines expressed the highest level in all cancer lines. In overall survival (OR) analysis, NaPi- II b mRNA high expressions were correlated to worse OR in OC patients. These results indicate that NaPi- II b may be a novel potential biomarker for determining the diagnosis and predicting the prognosis of OC.

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Multiple-biological matrices metabolomics identified new metabolite biomarkers for the precise diagnosis of pancreatic cancer and associated tissue metastasis

10.1101/2020.03.09.983239 ◽

2020 ◽

Author(s):

Xialin Luo ◽

Jingjing Liu ◽

Huaizhi Wang ◽

Haitao Lu

Keyword(s):

Pancreatic Cancer ◽

Clinical Setting ◽

Time Frame ◽

Therapeutic Interventions ◽

Healthy Controls ◽

Targeted Metabolomics ◽

Normal Tissues ◽

Glycocholic Acid ◽

Tumor Tissues ◽

Precise Diagnosis

AbstractPurposeTo improve clinical diagnosis and enhance therapeutic outcome, we figure out to identify and validate metabolite biomarkers from the plasma samples of patients with pancreatic cancer that can easily, sensitively and efficiently diagnose the onsite progression, and metastasis of the disease.Experimental DesignWe employed the newly developed precision-targeted metabolomics method to validate that many differential metabolites have the capacity to markedly distinguish patients with pancreatic cancer from healthy controls. To further enhance the specificity and selectivity of metabolite biomarkers, a dozen tumor tissues from PC patients and paired normal tissues were used to clinically validate the biomarker performance.ResultsWe eventually verified five new metabolite biomarkers in plasma (creatine, inosine, beta-sitosterol, sphinganine and glycocholic acid), which can be used to readily diagnose pancreatic cancer in a clinical setting. Excitingly, we proposed a panel biomarker by integrating these five individual metabolites into one pattern, demonstrating much higher accuracy and specificity to precisely diagnose pancreatic cancer than conventional biomarkers (CA125, CA19-9, CA242 and CEA); Moreover, we characterized succinic acid and gluconic acid as having a great capability to monitor the progression and metastasis of pancreatic cancer at different stages.ConclusionsTaken together, this metabolomics method was used to identify and validate metabolite biomarkers that can precisely and sensitively diagnose the onsite progression and metastasis of pancreatic cancer in a clinical setting. Furthermore, such effort should leave clinicians with the correct time frame to facilitate early and efficiently therapeutic interventions, which could largely improve the five-year survival rate of PC patients.

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SLC2A5 Correlated with Immune Infiltration: A Candidate Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma

Journal of Immunology Research ◽

10.1155/2021/9938397 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Lianxiang Luo ◽

Jiating Su ◽

Yushi Zheng ◽

Fangfang Huang ◽

Riming Huang ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Immune Cell ◽

Prognostic Biomarker ◽

Clinical Feature ◽

Lung Cancer Patients ◽

Immune Infiltration ◽

Kaplan Meier ◽

Tumor Tissues ◽

Kaplan Meier Plotter

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer with a relatively poor prognosis, requiring novel therapeutic approaches. Great advances in new immunotherapy strategies have shown encouraging results in lung cancer patients. This study is aimed at elucidating the function of SLC2A5 in the prognosis and pathogenesis of LUAD by analyzing public databases. The differential expression of SLC2A5 in various tissues from Oncomine, GEPIA, and other databases was obtained, and SLC2A5 expression at the protein level in normal and tumor tissues was detected with the use of the HPA database. Then, we used the UALCAN database to analyze the expression of SLC2A5 in different clinical feature subgroups. Notably, in both PrognoScan and Kaplan-Meier plotter databases, we found a certain association between SLC2A5 and poor OS outcomes in LUAD patients. Studies based on the TIMER database show a strong correlation between SLC2A5 expression and various immune cell infiltrates and markers. The data analysis in the UALCAN database showed that the decreased promoter methylation level of SLC2A5 in LUAD may lead to the high expression of SLC2A5. Finally, we used the LinkedOmics database to evaluate the SLC2A5-related coexpression and functional networks in LUAD and to investigate their role in tumor immunity. These findings suggest that SLC2A5 correlated with immune infiltration can be used as a candidate diagnostic and prognostic biomarker in LUAD patients.

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