Significance of HMMR Overexpression in 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.

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.

KIF23 Predict Immune Infiltration and Overall Survival in Gastric Cancer

10.21203/rs.3.rs-1222170/v1 ◽

2022 ◽

Author(s):

Maoshu Bai ◽

Xin Liu

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Area Under The Curve ◽

Enrichment Analysis ◽

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.

ADAM17 promotes the invasion of hepatocellular carcinoma via upregulation MMP21

Cancer Cell International ◽

10.1186/s12935-020-01556-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yuqi Xiang ◽

Liyu Liu ◽

Ying Wang ◽

Bo Li ◽

Jinwu Peng ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Gene Family ◽

Tumor Progression ◽

Molecular Mechanism ◽

Cell Invasion ◽

Expression Level ◽

Invasion And Metastasis ◽

Direct Association ◽

Abstract Background The upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, however the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified. Human matrix metalloproteinase 21 (MMP21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression. So far, nothing is known about the relationship between ADAM17 and MMP21. Methods In this study, the expression level of ADAM17 and MMP21 in HCC tissues was measured by immunohistochemistry. The Scratch wounding assay and Transwell were used to identify the invasion and metastasis ability. ELISA was used to evaluate the production of MMP21. Coimmunoprecipitation experiments demonstrated a direct association between ADAM17 and MMP21. HPLC was used to confirmed that ADAM17 participated in the maturation of MMP21. Results Our present data indicated that ADAM17 and MMP21 was significantly upregulated in human HCC tissues. Knockdown of ADAM17 in HCC inhibited cell invasion and metastasis. Moreover, ADAM17 regulates the secretion and expression of MMP21. Furthermore we discovered a direct association between ADAM17 and MMP21, and we also found MMP21 prodomain could be cleaved by ADAM17. Conclusion Our data suggest that ADAM17 plays an important role in the development of HCC invasion and metastasis and this function may be implement by MMP21.

Correlation analysis of RDM1 gene with immune infiltration and clinical prognosis of hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20203978 ◽

2021 ◽

Vol 41 (9) ◽

Author(s):

Chen Qiu ◽

Zuyin Li ◽

Wanyue Cao ◽

Xiaoni Cai ◽

Li Ye ◽

...

Keyword(s):

Mrna Expression ◽

Messenger Rna ◽

Immune Cell ◽

Liver Tumors ◽

Marker Genes ◽

Clinical Prognosis ◽

Immune Infiltration ◽

The Impact

Abstract Purpose: Liver hepatocellular carcinoma (LIHC) is one of the most common primary malignant liver tumors worldwide. The RAD52 motif-containing protein 1 (RDM1) has been shown to play a role in mediating DNA damage repair and homologous recombination. The present study was designed to determine the expression of RDM1 and its prognostic value as well as its relationship with immune infiltration in LIHC patients. Methods: Oncomine and Tumor Immunoassay Resource were used to assess the expression of RDM1. PrognoScan and Kaplan–Meier bioinformatics database were used to analyze the impact of clinical influencing factors on prognosis. Finally, the Tumor Immune Assessment Resource (TIMER) and Gene Expression Analysis Interactive Analysis (GEPIA) databases were used to detect the correlation between the expression of RDM1 and expression of marker genes related to immune infiltration. Immunohistochemistry (IHC) method was used to detect the expression level of RDM1 in 90 cases of hepatocellular carcinoma and adjacent normal liver tissues. Results: RDM1 expression was up-regulated in most cancers. The expression of RDM1 was remarkably higher than that of the corresponding normal control genes in LIHC tissues. The increase in RDM1 messenger RNA (mRNA) expression was closely related to the decreases in overall survival (OS) and progression-free survival (PFS). Additionally, the increase in RDM1 mRNA expression was closely related to the infiltration levels of macrophages, CD8+ T cells and B cells and was positively correlated with a variety of immune markers in LIHC. Conclusion: The findings of the present study demonstrate that RDM1 is a potentially valuable prognostic biomarker that can help determine the progression of cancer and is associated with immune cell infiltration in LIHC.

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.

Skeletal Muscle Volume Is an Independent Predictor of Survival after Sorafenib Treatment Failure for Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13092247 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2247

Author(s):

Issei Saeki ◽

Takahiro Yamasaki ◽

Yurika Yamauchi ◽

Taro Takami ◽

Tomokazu Kawaoka ◽

...

Keyword(s):

Skeletal Muscle ◽

Independent Predictor ◽

Muscle Volume ◽

Clinical Parameters ◽

Sorafenib Treatment ◽

Skeletal Muscle Index ◽

Free Survival ◽

Few studies exist on the relationship between post-progression survival (PPS) and skeletal muscle volume in hepatocellular carcinoma (HCC) patients receiving sorafenib. This study aimed to analyze the effects of muscle volume on clinical outcomes. We retrospectively enrolled 356 HCC patients. Various clinical parameters, including skeletal muscle index, were analyzed as predictors of overall survival (OS), progression-free survival (PFS), and PPS. Patients with high muscle volume showed longer survival or PPS than those with low muscle volume (median survival time: 12.8 vs. 9.5 months, p = 0.005; median PPS: 8.2 vs. 6.3 months, p = 0.015); however, no differences in PFS were found. Multivariate analysis indicated that muscle volume was an independent predictor of PPS and OS. Skeletal muscle volume was a PPS predictor in HCC patients receiving sorafenib. Therefore, survival can be prolonged by the upregulation of skeletal muscle volume, especially in HCC patients with skeletal muscle depletion.

ADAM17 promotes the metastasis of hepatocellular carcinoma via upregulation MMP21

10.21203/rs.3.rs-16968/v1 ◽

2020 ◽

Author(s):

Yuqi Xiang ◽

Liyu Liu ◽

Ying Wang ◽

Bo Li ◽

Jinwu Peng ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Gene Family ◽

Tumor Progression ◽

Molecular Mechanism ◽

Cell Invasion ◽

Expression Level ◽

Invasion And Metastasis ◽

Direct Association ◽

Abstract Background The upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, however the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified. Human matrix metalloproteinase 21 (MMP21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression. So far, nothing is known about the relationship between ADAM17 and MMP21. Methods In this study, the expression level of ADAM17 and MMP21 in HCC tissues was measured by immunohistochemistry. The Scratch wounding assay and Transwell were used to identify the invasion and metastasis ability. ELISA was used to evaluate the production of MMP21. Coimmunoprecipitation experiments demonstrated a direct association between ADAM17 and MMP21. HPLC was used to conﬁrmed that ADAM17 participated in the maturation of MMP21. Results Our present data indicated that ADAM17 and MMP21 was significantly upregulated in human HCC tissues. Knockdown of ADAM17 in HCC inhibited cell invasion and metastasis. Moreover, ADAM17 regulates the secretion and expression of MMP21. Furthermore we discovered a direct association between ADAM17 and MMP21, and we also found MMP21 prodomain could be cleaved by ADAM17. Conclusion Our data suggest that ADAM17 plays an important role in the development of HCC invasion and metastasis and this function may be implement by MMP21.

Comprehensive Analysis of the Expression, Prognosis and Immune Infiltration of KPNA Family in Hepatocellular Carcinoma

10.21203/rs.3.rs-757231/v1 ◽

2021 ◽

Author(s):

Xiangyi Chen ◽

Dechen Yu ◽

Hai-Yu Zhou ◽

XiaoBo Zhang ◽

Yicun Hu ◽

...

Keyword(s):

Immune Cell ◽

Enrichment Analysis ◽

Tumor Grade ◽

Mapk Signaling ◽

Clinicopathological Characteristics ◽

Expression Level ◽

Immune Infiltration ◽

Kaplan Meier ◽

Patient Prognosis

Abstract Background: The primary function of the Karyophorin alpha family (KPNAs) is to assist the transport of proteins from the cytoplasm to the nucleus. Studies have found that KPNAs are involved in the occurrence and development of a variety of tumors. However, the expression level of KPNAs family members in HCC, its influence on prognosis, its relationship with immune infiltration, and its clinical significance are still unclear.Methods: We used UALCAN, GEPIA, HPA, TIMER, Kaplan-Meier Plotter, CBioPortal, String and Metascape databases to analyze the expression and mutation of KPNAs in Hepatocellular carcinoma (HCC), the expression level of KPNAs and the prognosis of patients, tumor immune cell infiltration, HCC clinicopathological characteristics Relationship. Finally, the biological functions of KPNAs related genes are analyzed. Results: The protein and mRNA of KPNAs were significantly up-regulated in HCC, and their expression levels were closely related to the prognosis of patients and the clinical characteristics of the tumor (tumor grade, stage, etc.). In addition, KPNAs in HCC are prone to mutations, which are not conducive to the prognosis of patients. Moreover, the expression of HCC is positively correlated with the infiltration of immune cells. Enrichment analysis found that KPNAs-related genes are mainly related to biological processes such as nuclear and cytoplasmic signaling, protein chromosome localization, and their pathways mainly include cell cycle and MAPK signaling pathways. Conclusion: KPNAs are significantly related to the occurrence, development and patient prognosis of HCC and may become the target of HCC immunotherapy in the future.

ADAM17 promotes the invasion of hepatocellular carcinoma via upregulation MMP21

10.21203/rs.3.rs-16968/v2 ◽

2020 ◽

Author(s):

Yuqi Xiang ◽

Liyu Liu ◽

Ying Wang ◽

Bo Li ◽

Jinwu Peng ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Gene Family ◽

Tumor Progression ◽

Molecular Mechanism ◽

Cell Invasion ◽

Expression Level ◽

Invasion And Metastasis ◽

Direct Association ◽

Abstract Background: The upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, however the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified. Human matrix metalloproteinase 21 (MMP21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression. So far, nothing is known about the relationship between ADAM17 and MMP21.Methods: In this study, the expression level of ADAM17 and MMP21 in HCC tissues was measured by immunohistochemistry. The Scratch wounding assay and Transwell were used to identify the invasion and metastasis ability. ELISA was used to evaluate the production of MMP21. Coimmunoprecipitation experiments demonstrated a direct association between ADAM17 and MMP21. HPLC was used to conﬁrmed that ADAM17 participated in the maturation of MMP21.Results: Our present data indicated that ADAM17 and MMP21 was significantly upregulated in human HCC tissues. Knockdown of ADAM17 in HCC inhibited cell invasion and metastasis. Moreover, ADAM17 regulates the secretion and expression of MMP21. Furthermore we discovered a direct association between ADAM17 and MMP21, and we also found MMP21 prodomain could be cleaved by ADAM17.Conclusion: Our data suggest that ADAM17 plays an important role in the development of HCC invasion and metastasis and this function may be implement by MMP21.

Nuf2 Is a Prognostic-Related Biomarker and Correlated With Immune Infiltrates in Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.621373 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xingwei Xie ◽

Shanshan Jiang ◽

Xiang Li

Keyword(s):

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Free Survival ◽

Immune Infiltration ◽

Kaplan Meier ◽

Immune Biomarkers ◽

And Function

Nuf2 participates in the regulation of cell apoptosis and proliferation by regulating the binding of centromere and spindle microtubules to achieve the correct separation of chromosomes. Previous reports have suggested that Nuf2 may play a role in various human cancers. However, the mechanism and function of Nuf2 in the development of Hepatocellular carcinoma (HCC) remains uncertain. This study investigated the prognostic potential of Nuf2 and its relation with immune cell infiltration in HCC. Nuf2 expression in tumor cells was examined using the TIMER and Oncomine databases, and its prognostic potential was assessed via the Kaplan-Meier plotter and GEPIA databases. The relationships between Nuf2 and tumor immune infiltration were analyzed using TIMER. The relationships between Nuf2 and biomarkers of tumor immune infiltration were analyzed using TIMER and GEPIA. Here we revealed that Nuf2 expression increased in tumor tissues containing HCC, and this correlated with poor relapse-free survival, disease-specific survival, progression-free survival, and overall survival in patients with HCC regardless of grades, genders, races, drinking behaviors and other clinical factors. Additionally, high expression of Nuf2 was positively correlated with differential immune cell infiltration and various immune biomarkers. Our work demonstrated that Nuf2 could be a potential prognostic biomarker and could be related to tumor immune cell infiltration in HCC.