Overexpressed Pseudogene MT1L Associated with Tumor Immune Infiltrates and Indicates a Worse Prognosis in BLCA

Abstract Background BLCA is common cancer worldwide, aggressive, and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only part of these patients can benefit from ICT treatment. MT1L belongs to pseudogene, and a previous study has suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been illuminated. Methods Data was collected from TCGA, and logistic regression, Kaplan-Meier Plotter, and multivariate Cox analysis have been performed to demonstrate the correlation between pseudogene MT1L and prognosis in BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. And GSEA was performed to illuminate the potential biologic function. Results The expression of MT1L was decreased in BLCA. And it is positively connected with immune cells, like Tregs(ρ=0.708) and MDSCs(ρ=0.664). We also confirmed that MT1L is related to typical markers of immune cells，like PD-1, CTLA-4. Besides, the high MT1L expression level is related to the high stage of T, N, and the high grade in BLCA and the increased expression of MT1L was significantly associated with the shorter OS of BLCA patients (P<0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor of BLCA. Conclusion Collectively, our findings demonstrated that pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and serves as an independent prognostic biomarker in BLCA.

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Overexpressed pseudogene MT1L associated with tumor immune infiltrates and indicates a worse prognosis in BLCA

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02231-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yanpeng Ding ◽

Nuomin Liu ◽

Mengge Chen ◽

Yulian Xu ◽

Sha Fang ◽

...

Keyword(s):

Immune Cells ◽

Biological Function ◽

Prognostic Biomarker ◽

Poor Survival ◽

Common Cancer ◽

Kaplan Meier ◽

Cox Analysis ◽

Kaplan Meier Plotter ◽

Worse Prognosis

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.

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FCGBP Is a Prognostic Biomarker and Associated With Immune Infiltration in Glioma

Frontiers in Oncology ◽

10.3389/fonc.2021.769033 ◽

2022 ◽

Vol 11 ◽

Author(s):

Tengfeng Yan ◽

Daofeng Tian ◽

Junhui Chen ◽

Yinqiu Tan ◽

Yue Cheng ◽

...

Keyword(s):

Immune Response ◽

Predictive Marker ◽

Immune Markers ◽

Immune Infiltration ◽

Pathway Enrichment ◽

Kaplan Meier ◽

Igg Binding ◽

Kaplan Meier Plotter ◽

Worse Prognosis

The Fc Fragment of IgG Binding Protein (FCGBP) has been proven to participate in intestinal tumor immunity. However, the biological role of FCGBP has remained unclear in glioma. The differential expression of FCGBP was explored by Oncomine and GEPIA databases. The effect of FCGBP on prognosis was analyzed via Kaplan–Meier plotter and GEPIA. The Tumor Immune Estimation Resource (TIMER) tool was used to determine the correlations of FCGBP expression with tumor immune infiltration. Firstly, FCGBP was highly expressed in glioma and correlated with a worse prognosis. Gene Ontology (GO) and KEGG pathway enrichment analyses revealed that the differentially expressed genes (DEGs) and co-expression genes of FCGBP were mainly involved in the immune response. Furthermore, FCGBP expression was positively associated with multiple immune cells infiltrates as well as the expression levels of multiple immune markers in glioma. FCGBP co-expression networks mostly participated in the regulation of immune response. Finally, immunohistochemistry (IHC) assays were conducted to explore the expression of FCGBP, PD-L1, CCL2 and CD8 in glioma and correlations between them. We found that PDL1 and FCGBP were synchronously upregulated in glioma tissues. These findings revealed a new mechanism by which FCGBP participates in the immune tolerance of glioma, and implied the potential of FCGBP as a therapeutic target or predictive marker for patients.

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APOC1 is a Potential Prognostic Biomarker and Correlated With Immune Infiltration in ESCC

10.21203/rs.3.rs-98085/v1 ◽

2020 ◽

Author(s):

Jia-yi XIE ◽

Ming Liu ◽

Yaxin Luo ◽

Zhen Wang ◽

Zhenghong Lu ◽

...

Keyword(s):

T Cells ◽

Transcription Factors ◽

Cd8 T Cells ◽

Immune Cells ◽

Poor Prognosis ◽

Killer Cell ◽

Gene Set Enrichment Analysis ◽

Immune Infiltration ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract PurposeEsophageal cancer (EC) is the sixth leading cause of cancer death worldwide. Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of EC. Identifying diagnostic biomarkers for ESCC is necessary for cancer practice. Increasing evidence illustrates that apolipoprotein C-1 (APOC1) participates in the carcinogenesis. However, the biological function of APOC1 in ESCC remains unclear. Patients and methodsWe investigated the expression level of APOC1 using TIMER2.0 and GEO databases, the prognostic value of APOC1 in ESCC using Kaplan-Meier plotter and TCGA databases. We used LinkedOmics to identify co-expressed genes with APOC1 and perform GO and KEGG pathway analysis. The target networks of kinases, miRNAs and transcription factors were predicted by gene set enrichment analysis (GSEA). The correlations between APOC1 and immune infiltration were calculated using TIMER2.0 and CIBERSORT databases. We further performed the prognostic analysis based on APOC1 expression levels in related immune cells subgroups via Kaplan-Meier plotter database. ResultsAPOC1 was found overexpressed in tumor tissues in multiple ESCC cohorts and high APOC1 expression was related to a dismal prognosis. Multivariate analysis confirmed that APOC1 overexpression was an independent indicator of poor OS. Functional network analysis indicated that APOC1 might regulate the natural killer cell mediated cytotoxicity, phagosome, AMPK and hippo signaling through pathways involving some cancer-related kinases, miRNA and transcription factors. Immune infiltration analysis showed that APOC1 was significantly positively correlated with M0 macrophages cells, M1 macrophages cells and activated NK cells, negatively correlated with regulatory T cells, CD8 T cells, neutrophils and monocytes. High APOC1 expression had a poor prognosis in server immune cells subgroups in ESCC, including decreased CD8+ T cells subgroups. ConclusionThese findings suggest that increased expression of APOC1 is related to poor prognosis and immune infiltration in ESCC. APOC1 holds promise for serving as a valuable diagnostic and prognostic marker in ESCC.

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Low TWEAK expression indicates poor survival and is correlated with sparse TIICs in lung adenocarcinoma (LUAD).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21017 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21017-e21017

Author(s):

Jinchun Wu ◽

Xianyu Liu ◽

Yanhua Mou ◽

Shan Zeng ◽

Jin Zhang ◽

...

Keyword(s):

T Cells ◽

Lung Adenocarcinoma ◽

Cd8 T Cells ◽

Immune Cells ◽

Poor Prognosis ◽

Immune Escape ◽

Underlying Mechanism ◽

Memory Cd8 T Cells ◽

Kaplan Meier ◽

Kaplan Meier Plotter

e21017 Background: Lung adenocarcinoma (LUAD) occupies the most of non-small cell lung cancer (NSCLC) and shows promising response to PD-1 immunotherapy, but immune escape will cause treatment failure indicating poor prognosis. TWEAK (Tumor necrosis factor-related weak inducer of apoptosis, also known as TNFSF12) combining with its receptor FN14 (fibroblast growth factor–inducible 14) mediates crucial innate and adaptive immune pathways to promote the progression of multiple autoimmune diseases. So we assumed that TWEAK is a prognostic predictor and related with tumor-infiltrating immune cells (TIICs) in LUAD. Methods: TWEAK expression of LUAD was primarily investigated in The Cancer Immunome Atlas (TCIA) and then validated in Tumor Immune Estimation Resource (TIMER) databases. We assessed the effect of TWEAK on the survival via the Kaplan-Meier plotter, GEPIA2 (gene expression profiling interactive analysis) and PrognoScan databases. The relation between TWEAK and TIICs was explored in TIMER and TCIA, as well as the correlation of TWEAK and FN14 was analyzed in TIMER and GEPIA2. Results: Low TWEAK expression was significantly associated with poor relapse-free survival (RFS) (HR = 0.62, 95% CI = 0.4~0.97, logrank P = 0.035) and overall survival (OS) (HR = 0.61, 95% CI = 0.46~0.83, logrank P = 0.0012) in LUAD from Kaplan-Meier plotter. Similar impacts of TWEAK on the survival were validated in GEPIA2 and four independent cohorts from PrognoScan (jacob-00182-CANDF, GSE13213, jacob-00182-MSK and GSE31210). Moreover, reduced TWEAK expression was closely related with the paucity of TIICs which contributed to poor OS, including central memory CD8 T cells, plasmacytoid dendritic cells, activated CD8 T cells, monocytes, T follicular helper cells, immature B cells and eosinophils. In addition, TWEAK expression was positively related with the expression level of FN14 in both GEPIA2(R = 0.13, P= 0.0031) and TIMER (partial.cor = 0.212, P= 2.04e-06). Conclusions: Low TWEAK expression maybe indicate poor prognosis in LUAD, and correlated with the impaired infiltration of immune cells in the tumor region. The defective TWEAK/FN14 pathway possibly accounts for these observations, but the underlying mechanism needs to be further explored.

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Upregulated CCNE1 Correlates with Poor Prognosis, Tumor Immune Infiltration and Escape in Breast Cancer

10.21203/rs.3.rs-966772/v1 ◽

2021 ◽

Author(s):

Jiaxi Feng ◽

Yanan Hu ◽

Dan Liu ◽

Shanshan Wang ◽

Mengci Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Immune Cells ◽

Poor Prognosis ◽

Immune Cell ◽

High Expression ◽

Expression Level ◽

Immune Cell Infiltration ◽

Immune Infiltration ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract Background Breast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.Methods At first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.Results The results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell inﬁltration, biomarkers of immune cells, and immune checkpoint expression in BC. conclusions In summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.

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Identification of Prognostic Biomarkers Among DAAM1, FHOD1,FMN2 and INF2 in Breast Cancer Patients

10.21203/rs.3.rs-742870/v1 ◽

2021 ◽

Author(s):

Yin-Hai Dai ◽

Fuping Li ◽

Wei-Jie Kong ◽

Xue-Qin Zhang ◽

Mao Wang ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

Immune Cells ◽

Survival Data ◽

Mrna Level ◽

Mrna Levels ◽

Breast Cancer Patients ◽

Kaplan Meier ◽

Migration Of Cells ◽

Kaplan Meier Plotter

Abstract Background:The formin family proteins are main regulators of actin filaments, which play a crucial role in the migration of cells and carcinogenesis.The specific functions of the formin family proteins in breast cancer still remain unknown.To dissolve this problem,we selected four formin proteins including DAAM1,FHOD1, FMN2 and INF2 and investigated their mRNA expression and survival data in BC(breast carcinoma) patients using diverse databases.Methods:we used these databases including Oncomine, Ualcan, GEPIA 2,HumanProtein Atlas,Metascape,Kaplan-Meier plotter,cBioPortal and TIMER and the software of Cytoscape in our study.Results:DAAM1 and FMN2 were lowly expressed in BC tissues,while FHOD1 and INF2 were highly expressed in BC tissues.The expression levels of DAAM1, FMN2 and FHOD1 were relevant to major subclasses,and the mRNA level of FHOD1 was related to cancer staging.Moreover,High mRNA levels of FHOD1 and INF2 were relevant to poorer prognosis of BC patients,while low mRNA level of DAAM1 was correlated with better prognosis.we also found that there were significant associations between the expressions of DAAM1,FHOD1,FMN2 and INF2 and six types of infiltrated immune cells(B Cells,CD4+T cells,CD8+T cells, neutrophil,macrophage,and dendritic cell).Conclusions:our study indicated that FHOD1 and INF2 were potential biomarkers to identify short survival of BC patients,FMN2 was potential prognostic marker to suggest favorable survival of BC patients.

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

10.21203/rs.3.rs-270956/v1 ◽

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.

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Bioinformatics Analysis and Insights for The Role of COMMD7 in Hepatocellular Carcinoma

10.21203/rs.3.rs-79438/v1 ◽

2020 ◽

Author(s):

Xuehui Peng ◽

Yonggang He ◽

Xiaobing Huang ◽

Nan You ◽

Huiying Gu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Bioinformatics Analysis ◽

Tissue Expression ◽

The Cancer Genome Atlas ◽

Research Progress ◽

Kaplan Meier ◽

Tumor Tissues ◽

Cancer Genome Atlas ◽

Kaplan Meier Plotter

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions：This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.

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Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells

Biomolecules ◽

10.3390/biom11020246 ◽

2021 ◽

Vol 11 (2) ◽

pp. 246

Author(s):

Daiana L. Vitale ◽

Ilaria Caon ◽

Arianna Parnigoni ◽

Ina Sevic ◽

Fiorella M. Spinelli ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Prognostic Marker ◽

Glucose Dehydrogenase ◽

Breast Cancer Patients ◽

Kaplan Meier ◽

Initial Identification ◽

Prognosis Marker ◽

Kaplan Meier Plotter ◽

Worse Prognosis

UDP-glucose-dehydrogenase (UGDH) synthesizes UDP-glucuronic acid. It is involved in epirubicin detoxification and hyaluronan synthesis. This work aimed to evaluate the effect of UGDH knockdown on epirubicin response and hyaluronan metabolism in MDA-MB-231 breast cancer cells. Additionally, the aim was to determine UGDH as a possible prognosis marker in breast cancer. We studied UGDH expression in tumors and adjacent tissue from breast cancer patients. The prognostic value of UGDH was studied using a public Kaplan–Meier plotter. MDA-MB-231 cells were knocked-down for UGDH and treated with epirubicin. Epirubicin-accumulation and apoptosis were analyzed by flow cytometry. Hyaluronan-coated matrix and metabolism were determined. Autophagic-LC3-II was studied by Western blot and confocal microscopy. Epirubicin accumulation increased and apoptosis decreased during UGDH knockdown. Hyaluronan-coated matrix increased and a positive modulation of autophagy was detected. Higher levels of UGDH were correlated with worse prognosis in triple-negative breast cancer patients that received chemotherapy. High expression of UGDH was found in tumoral tissue from HER2--patients. However, UGDH knockdown contributes to epirubicin resistance, which might be associated with increases in the expression, deposition and catabolism of hyaluronan. The results obtained allowed us to propose UGDH as a new prognostic marker in breast cancer, positively associated with development of epirubicin resistance and modulation of extracellular matrix.

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Distinct functions and prognostic values of RORs in gastric cancer

Open Medicine ◽

10.1515/med-2020-0406 ◽

2020 ◽

Vol 15 (1) ◽

pp. 424-434

Author(s):

Feng Gu ◽

Yuming Liu ◽

Yuan Liu ◽

Shujie Cheng ◽

Jihong Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Retinoic Acid Receptor ◽

Wnt Signaling Pathway ◽

Her2 Status ◽

Orphan Receptors ◽

Kaplan Meier ◽

And Migration ◽

Kaplan Meier Plotter ◽

Proliferation And Migration

AbstractRetinoic acid receptor-related orphan receptors (RORs) are frequently abnormally expressed in several human malignancies, including gastric cancer (GC). RORs are involved in the development and progression of GC through Wnt signaling pathway receptors and other common receptors. However, the prognostic roles of individual RORs in patients with GC remain elusive. We accessed the prognostic roles of three RORs (RORα, RORβ, and RORγ) through “The Kaplan–Meier plotter” (KM plotter) database in patients with GC. For all patients with GC who were followed for 20 years, the low mRNA expression of all three RORs showed a significant correlation with better outcomes. We further accessed the prognostic value of individual RORs in different clinical pathological features including Lauren classification, clinical stages, pathological grades, HER2 status, and different treatments methods. The RORs demonstrated critical prognostic roles in GC. Expressions of RORs were higher in GC tissues when compared with normal gastric tissues. Moreover, knockdown of RORs significantly inhibited cell proliferation and migration, suggesting an oncogenic role of RORs in human GC. These findings suggest potential roles of RORs as biomarkers for GC prognosis and as oncogenes in GC.

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