GEPIA Database Research Articles

SAMD4A serves as a negative prognostic marker for gastric cancer patients

IntroductionThe incidence and mortality of gastric cancer remain high in the world. We aim to explore the role of SAMD4A in gastric cancer. MethodsThe expression of SAMD4A was up-regulated in gastric adenocarcinoma and the expression level of SAMD4A in gastric adenocarcinoma and adjacent normal tissues was verified by RT-qPCR. Immunohistochemical showed that SAMD4A was mainly located in the cytoplasm. ResultThe result showed that the expression of SAMD4A was positively correlated with the depth of invasion, the number of lymph node metastasis, and the clinical stage in patients with gastric adenocarcinoma. Survival analysis of GEPIA database showed that the overall survival of gastric adenocarcinoma patients with positive SAMD4A expression was lower than that of the negative group. Gastric cancer cell lines with knockdown of the SAMD4A gene were used to observe the differences in cell proliferation, invasion, and migration abilities between the knockdown group and the control group. The results showed that the proliferation, invasion, and migration abilities of the SAMD4A knockdown group were both weakened compared with the control group. This study is the first to find that the expression level of SAMD4A in gastric cancer is higher than that in the adjacent group and is associated with poor prognosis of patients. SAMD4A promotes the proliferation, invasion, and migration of gastric adenocarcinoma cells. ConclusionThis indicates that SAMD4A plays an important role in the occurrence and development of gastric cancer, and is expected to be an effective indicator for the diagnosis and evaluation of the prognosis of gastric cancer.

Forkhead Box P4 promotes the proliferation of cells in colorectal adenocarcinoma

Abstract Objectives Forkhead Box P4 (FOXP4) is a transcription factor that promotes tumor formation and progression. However, studies on its roles in colorectal adenocarcinoma (CRAC) and cell proliferation regulation are few to date. This work investigates the expression of FOXP4 in CRAC, explores the characteristic of FOXP4 in different clinicopathological features, and analyzes its regulation of cell proliferation. Methods The GEPIA database was used to predict the trend of FOXP4 expression in colon cancer and normal mucosa. Tumor tissue and normal paracancerous mucosal tissue were sampled from 64 cases diagnosed with CRAC and who were receiving radical surgery at Tianjin Hospital from January 2017 and December 2022. FOXP4 and proliferating cell nuclear antigen (PCNA) were detected by the immunohistochemistry EnVision method. The colon cancer cell lines SW480, HCT15, and SW620 and the normal colon cell line NCM460 were selected, and expression of FOXP4 was detected by the Western blot method. The siRNA-FOXP4 plasmid was synthesized and transfected with SW480 and HCT15 cell lines, respectively, to establish si-FOXP4 groups, and empty vector transfection group (NC-FOXP4) and blank control group (NC) was set up. The expression levels of FOXP4 and PCNA were detected by the Western blot method, while the cell proliferation activity was assessed using CCK-8. Normally distributed quantitative data were compared between two and more groups with ANOVA (SNK-based pairwise comparison), while intergroup enumeration data comparisons were performed through χ 2 test and assessed through linear correlation analysis. Results GEPIA-based prediction shows a potential rise in FOXP4 expression in colon cancer. The rate of positive FOXP4 expression is significantly higher in CRAC tissue than in normal mucosa (p<0.05). The difference in FOXP4 is statistically significant in the comparison of maximum tumor diameter and depth of invasion in CRAC (p<0.05) but not in the comparison of gender, age, degree of differentiation, tumor focus, tumor embolism, and lymph node metastasis (p>0.05). The expression levels of FOXP4 and PCNA in CRAC are positively correlated (p<0.05). FOXP4 expression is significantly higher in cell lines SW480, HCT15, and SW620 than in cell line NCM460. The cell proliferation activity and PCNA expression are significantly lower in si-FOXP4 group than in NC-FOXP4 and NC groups for cell lines SW480 and HCT15. Conclusions FOXP4 is highly expressed and has a proliferative effect on tumor cells in CRAC.

An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma

BackgroundDiffuse large B-cell lymphoma (DLBCL) is one of the most aggressive malignant tumors. Chromobox (CBX) family plays the role of oncogenes in various malignancies.MethodsThe transcriptional and protein levels of CBX family were confirmed by GEPIA, Oncomine, CCLE, and HPA database. Screening of co-expressed genes and gene function enrichment analysis were performed by GeneMANIA and DAVID 6.8. The prognostic value, immune cell infiltration and drug sensitivity analysis of CBX family in DLBCL were performed by Genomicscape, TIMER2.0, and GSCALite database. Confirmatory Tests of CBX family protein expression in DLBCL were performed by immunohistochemistry.ResultsThe mRNA and protein expressions of CBX1/2/3/5/6 were higher in DLBCL tissues than control groups. Enrichment analysis showed that the functions of CBX family were mainly related to chromatin remodeling, methylation-dependent protein binding, and VEGF signaling pathway. The high mRNA expressions of CBX2/3/5/6 were identified to be associated with short overall survival (OS) in DLBCL patients. Multivariate COX regression indicated that CBX3 was independent prognostic marker. Immune infiltration analysis revealed that the mRNA expressions of CBX family (especially CBX1, CBX5, and CBX6) in DLBCL were significantly correlated with the infiltration of most immune cells (including B cells, CD8 + T cells, CD4 + T cells, neutrophils, monocytes, macrophages, and Treg cells). Meanwhile, there was a strong correlation between the expression levels of CBX1/5/6 and surface markers of immune cells, such as the widely studied PVR-like protein receptor/ligand and PDL-1 immune checkpoint. Notably, our study found that DLBCL cells with CBX1 over-expression were resistant to the common anti-tumor drugs, but CBX2/5 had two polarities. Finally, we confirmed the higher expressions of CBX1/2/3/5/6 in DLBCL tissues compared with control groups by immunohistochemistry.ConclusionWe provided a detailed analysis of the relationship between the CBX family and the prognosis of DLBCL. Distinguished from other studies, We found that high mRNA expressions of CBX2/3/5/6 were associated with poor prognosis in DLBCL patients, and Multivariate COX regression indicated that CBX3 was independent prognostic marker. Besides, our study also found an association between the CBX family and anti-tumour drug resistance, and provided a relationship between CBX family expression and immune cell infiltration.

CD93 overexpresses in liver hepatocellular carcinoma and represents a potential immunotherapy target.

Liver hepatocellular carcinoma (LIHC) is one of the malignant tumors with high incidence as well as high death, which is ranked as the sixth most common tumor and the third highest mortality worldwide. CD93, a transmembrane protein, has been widely reported to play an important role in different types of diseases, including many types of cancer by mainly functioning in extracellular matrix formation and vascular maturation. However, there are few researches focusing on the role and potential function of CD93 in LIHC. In this study, we comprehensively analyzed the relationship between CD93 and LIHC. We not only discovered transcriptional expression of CD93 in LIHC by using the TIMER, GEPIA and UALCAN database, but also performed WB and IHC to verify the protein expression of CD93 in LIHC. Meantime, Kaplan-Meier Plotter Database Analysis were used to assess the prognosis of CD93 in LIHC. After knowing close correlation between CD93 expression and LIHC, there were STRING, GeneMania and GO and KEGG enrichment analyses to find how CD93 functions in LIHC. We further applied CIBERSORT Algorithm to explore the correlation between CD93 and immune cells and evaluate prognostic value of CD93 based on them in LIHC patients. The transcriptional and protein expression of CD93 were both obviously increased in LIHC by above methods. There was also a significant and close correlation between the expression of CD93 and the prognosis of LIHC patients by using Kaplan-Meier Analysis, which showed that LIHC patients with elevated expression of CD93 were associated with a predicted poor prognosis. We found that the functions of CD93 in different cancers are mainly related to Insulin like growth factor binding protein 7 Gene (IGFBP7)/CD93 pathway via STRING, GeneMania and functional enrichment analyses. Further, our data obtained from CIBERSORT Algorithm suggested CD93 was also associated with the immune response. There is a close positive correlation between CD93 expression and the infiltration levels of all six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). Importantly, CD93 can affect the prognosis of patients with LIHC partially due to immune infiltration. Our results demonstrated CD93 may be a candidate predictor of clinical prognosis and immunotherapy response in LIHC.

UVB promotes melanogenesis by regulating METTL3.

Ultraviolet (UV) radiation is the primary exogenous inducer of skin pigmentation, although the mechanism has not been fully elucidated. N6-methyladenosine (m6 A) modification is one of the key epigenetic form of gene regulation that affects multiple biological processes. The aim of this study was to explore the role and underlying mechanisms of m6 A modification in UVB-induced melanogenesis. Low-dose UVB increased global m6 A modification in melanocytes (MCs) and MNT1 melanoma cell line. The GEPIA database predicted that methyltransferase METTL3 is positively correlated with the melanogenic transcription factor MITF in the sun-exposed skin tissues. After METTL3 respectively overexpressed and knocked down in the MNT1, the melanin content and melanogenesis-related genes were significantly upregulated after overexpression of METTL3, especially with UVB irradiation, and downregulated after METTL3 knockdown. METTL3 levels were also higher in melanocytic nevi with high melanin content. METTL3 overexpression and knockdown also altered the protein level of YAP1. SRAMP analysis predicted four high-potential m6 A modification sites on YAP1 mRNA, of which three were confirmed by methylated RNA immunoprecipitation. Inhibition of YAP1 expression can partially reverse melanogenesis induced by overexpression of METTL3. In conclusion, UVB irradiation promotes global m6 A modification in MCs and upregulates METTL3, which increases the expression level of YAP1 through m6 A modification, thereby activating the co-transcription factor TEAD1 and promoting melanogenesis.

E2F1‑mediated RAB34 upregulation accelerates the proliferation and inhibits the cell cycle arrest and apoptosis of acute myeloid leukemia cells.

Acute myeloid leukemia (AML) is a malignant disease that is mainly arisen from myeloid stem/progenitor cells. The pathogenesis of AML is complex. Ras-related protein member RAS oncogene GTPases (RAB) 34 protein has been reported to serve an important role in the development of cancer. However, to the best of our knowledge, the role of RAB34 in AML has not been previously reported. The GEPIA database was used to predict the expression levels of RAB34 in patients with AML. Reverse transcription-quantitative PCR and western blotting were used to detect the expression of RAB34 in AML cell lines. Cell transfection with short hairpin (sh)RNAs targeting RAB34 was used to interfere with RAB34 expression. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine staining were used to measure cell proliferation. Flow cytometry was used to investigate cell cycle distribution and apoptosis. Western blotting was used to assess the protein expression levels of RAB34 and E2F transcription factor 1 (E2F1), and cell cycle- and apoptosis-associated proteins, including Bcl-2, Bax, CDK4, CDK8 and cyclin D1. The potential binding between E2F1 and RAB34 was then verified by luciferase reporter and chromatin immunoprecipitation assays. Subsequently, cells were co-transfected with RAB34 shRNA and the E2F1 overexpression plasmid before cell proliferation, cell cycle and apoptosis were analyzed further. The expression of RAB34 was found to be significantly increased in AML cell lines. Knocking down RAB34 expression in AML cells was found to significantly inhibit cell proliferation, induce cell cycle arrest and promote apoptosis. E2F1 activated the transcription of RAB34 and E2F1 elevation reversed the impacts of RAB34 silencing on cell proliferation, cell cycle and apoptosis in AML. Therefore, these findings suggest that E2F1-mediated RAB34 upregulation may accelerate the malignant progression of AML.

In-Silico CLEC5A mRNA expression analysis to predict Dengue susceptibility in cancer patients

Dengue fever is the fastest-growing infectious disease in the world. It is the leading vector-borne viral neglected tropical disease. The most acute immune response to dengue virus infection is dengue shock syndrome and hemorrhagic fever, which is due to the activation of CLEC5A C-type lectin domain family 5, member A (CLEC5A). It is a cell surface receptor, and its well-known ligand is the dengue virus. It gets activated by the attachment of dengue virion, which, as a result, phosphorylates its adaptor protein DAP12 leading to the induction of various pro-inflammatory cytokines. Clinical data suggested that the kidneys and lungs are among the major hit organs in the case of severe dengue infection. Here we predict kidney and lung cancer patients are vulnerable to dengue virus infection as CLEC5A mRNA expression in tumor samples using publicly available software such as TIMER and GEPIA database. We also identified the immunomodulatory role CLEC5A gene therefore targeting it could be a vital tool to cure dengue.

Pan-cancer analysis of the prognostic and immunological role of GJB2: a potential target for survival and immunotherapy.

GJB2 plays an essential role in the growth and progression of several cancers. However, asystematic pan-cancer analysis of GJB2 is lacking. Therefore, in this study, we performed a comprehensive pan-cancer analysis to determine the potential role of GJB2 in prognostic prediction and cancer immunotherapy response. The differential expression of GJB2 in the tumor and adjacent normal tissues of various cancer types was analyzed using the TIMER, GEPIA, and Sangerbox databases. GEPIA and Kaplan-Meier plotter databases were used to analyze the survival outcomes based on GJB2 expression levels in pan-cancer. Furthermore, the association of GJB2 expression with the immune checkpoint (ICP) genes, tumor mutational load (TMB), microsatellite instability (MSI), neoantigens, and tumor infiltration of immune cells was analyzed using via the Sangerbox database. The cBioPortal database was used to determine the characteristics of GJB2 gene alterations in the cancer tissues. The STRING database was used to identify the GJB2-binding proteins. GEPIA database was used to identify the GJB2 co-expressed genes. DAVID was used to perform the functional enrichment analysis of gene ontology (GO) terms and KEGG pathways associated with GJB2. Finally, the mechanistic role of GJB2 in pancreatic adenocarcinoma (PAAD) was analyzed using the LinkedOmics database. The GJB2 gene was highly expressed in a variety of tumors. Furthermore, GJB2 expression levels showed significant positive or negative association with the survival outcomes in various cancers. GJB2 expression levels cor related with tumor mutational burden, microsatellite instability, neoantigens, and tumor infiltration of immune cells in multiple cancers. This suggested that GJB2 played a critical role in the tumor microenvironment. Functional enrichment analysis showed that the biological role of GJB2 in tumors included modulation of gap junction-mediated intercellular transport, regulation of cell communication by electrical coupling, ion transmembrane transport, autocrine signaling, apoptotic signaling pathway, NOD-like receptor signaling pathway, p53 signaling pathway, and PI3K-Akt signaling pathway. Our study demonstrated that GJB2 played a significant role in tumorigenesis and tumor immunity in multiple cancers. Furthermore, GJB2 is a potential prognostic biomarker and a promising therapeutic target in multiple types of cancers.

Annexin A9 promotes cell proliferation by regulating the Wnt signaling pathway in colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Expression of Annexin A9 (ANXA9), a member of the annexin A family, is upregulated in CRC. However, the molecular role of ANXA9 in CRC remains unknown. In the present study, we aimed to investigate the function of ANXA9 and to elucidate the mechanisms underlying its regulation in CRC. In this study, mRNA expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and GEPIA database, respectively. Kaplan–Meier analysis was used to analyze the survival rates. LinkedOmics and Metascape databases were used to explore the potential mechanisms of regulation of ANXA9 and to identify genes co-expressed with ANXA9. Finally, in vitro experiments were used to evaluate the function of ANXA9 and explore potential mechanisms. We found that ANXA9 expression was significantly elevated in CRC tissue and cells. High ANXA9 expression was associated with shorter overall survival, poorer disease specific survival, as well as with patient age, clinical stage, M stage, and OS events in CRC. Knockdown of ANXA9 inhibited cell proliferation, invasion, migratory potential, and cell cycle arrest. Mechanistically, functional analysis revealed that genes co-expressed with ANXA9 were mainly enriched in the Wnt signaling pathway. ANXA9 deletion suppressed cell proliferation via the Wnt signaling pathway, while Wnt activation reversed the effects of ANXA9. In conclusion, ANXA9 may promote CRC progression by regulating the Wnt signaling pathway and may be a potential diagnostic biomarker in the clinical management of CRC.

Low expression of acyl-CoA thioesterase 13 is associated with poor prognosis in ovarian serous cystadenocarcinoma.

Objective: Acyl-CoA thioesterase 13 (ACOT13) encodes a member of the thioesterase superfamily. It has not been reported in ovarian cancer. This research aimed at evaluating the expression and prognostic value of ACOT13 in ovarian serous cystadenocarcinoma (OSC). Methods: We extracted and analyzed TCGA, GEPIA, THPA, GTEx, miRWalk, and GDSC databases to investigate the potential carcinogenic mechanism of ACOT13 in OSC, including the correlation of ACOT13 with prognosis, immune checkpoint, tumor mutational burden (TMB), and 50% inhibition concentration (IC50) score. The incidence of endpoint events was compared with Kaplan-Meier survival analysis. Independent prognostic factors for OSC were evaluated with univariate and multivariate Cox regression analyses, and a nomogram was established. Results: The expression of ACOT13 was increased in OSC and correlated with tumor stage, with higher expression in stages I and II than in stages III and IV. Besides, it was observed that low expression of ACOT13 is correlated with poor overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) in patients with OSC. There was a positive correlation between ACOT13 expression and immune checkpoint sialic acid-binding Ig-like lectin (SIGLEC) 15 and TMB. Patients with low ACOT13 expression had higher cisplatin IC50 scores. Conclusion: ACOT13 is an independent prognostic factor and a promising clinical target for OSC. In the future, the carcinogenic mechanism and clinical application value of ACOT13 in ovarian cancer need to be further studied.

Disruptions of Circadian Genes in Cutaneous Melanoma-An In Silico Analysis of Transcriptome Databases.

Circadian genes are a set of genes that regulate the body's internal clock and influence various physiological processes, including sleep-wake cycles, metabolism and immune function. Skin cutaneous melanoma (SKCM) is a type of skin cancer that arises from the pigment-producing cells in the skin and is the most deadly form of skin cancer. This study has investigated the relevance of circadian gene expression and immune infiltrations in the outcomes of cutaneous melanoma patients. In the present study, in silico methods based on the GEPIa, TIMER 2.0 and cBioPortal databases were performed, so as to investigate the transcript level and prognostic value of 24 circadian genes in SKCM and their relationship with the immune infiltration level. The in silico analysis showed that significantly more than half of the investigated circadian genes have an altered transcript pattern in cutaneous melanoma compared to normal skin. The mRNA levels of TIMELES and BHLHE41 were upregulated, whereas those of NFIL3, BMAL1, HLF, TEF, RORA, RORC, NR1D1, PER1, PER2, PER3, CRY2 and BHLHE40 were downregulated. The presented research shows that SKCM patients with at least one alteration of their circadian genes have decreased overall survival. Additionally, majority of the circadian genes are significantly corelated with the immune cells' infiltration level. The strongest correlation was found for neutrophils and was followed by circadian genes: NR1D2 r = 0.52 p < 0.0001, BMAL1 r = 0.509 p < 0.0001; CLOCK r = 0.45 p < 0.0001; CSNKA1A1 r = 0.45 p < 0.0001; RORA r = 0.44 p < 0.0001. The infiltration level of immune cells in skin tumors has been associated with patient prognosis and treatment response. Circadian regulation of immune cell infiltration may further contribute to these prognostic and predictive markers. Examining the correlation between circadian rhythm and immune cell infiltration can provide valuable insights into disease progression and guide personalized treatment decisions.

Screening and validation of potential markers associated with uterine corpus endometrial carcinoma and polycystic ovary syndrome based on bioinformatics methods

Background: Endometrial cancer (UCEC) is a commonly occurring tumor in females, and polycystic ovary syndrome (PCOS) is closely related to UCEC, but the molecular mechanisms remain unclear. This article aims to explore potential molecular mechanisms in UCEC and PCOS, as well as identify prognostic genes for UCEC.Methods: Bioinformatics methods were employed to screen for DEGs in UCEC and PCOS. The shared DEGs were analyzed by constructing a protein-protein interaction (PPI) network using the String database and Cytoscape software. The enrichment analysis was performed using Metascape. The shared DEGs associated with the prognosis of UCEC were identified through univariate and lasso Cox regression methods. A multivariate Cox regression model was constructed and internally validated. The expression and test efficiency of the key prognostic genes were verified using external datasets for UCEC and PCOS. Furthermore, the Gepia database was utilized to analyze the expression of key prognostic genes and their correlation with the disease-free survival (RFS) of UCEC. Tumor mutation burden (TMB), immune infiltration, and the correlation of immune cells were assessed for the prognostic genes of UCEC.Results: There were 151 shared DEGs identified between UCEC and PCOS through bioinformatics screening. These shared DEGs were primarily enriched in leukocyte activation. Following model construction and verification, nine genes were determined to be prognostic for UCEC from the shared DEGs. Among them, TSPYL5, KCNJ15, RTN1, HMOX1, DCAF12L1, VNN2, and ANXA1 were confirmed as prognostic genes in UCEC through external validation. Additionally, RTN1 was identified as a key gene in both UCEC and PCOS. Gepia analysis revealed that higher expression of RTN1 was associated with RFS in UCEC. Immune infiltration analysis of the shared DEGs demonstrated significant differences in the expression of various immune cells between UCEC high and low TMB groups. The seven key prognostic genes in UCEC exhibited regulatory relationships with immune cells.Conclusion: This study identified TSPYL5, KCNJ15, RTN1, HMOX1, DCAF12L1, VNN2, and ANXA1 as the key prognostic DEGs of UCEC. These genes are associated with UCEC survival, TMB, immune cell infiltration, and immune cell regulation. Among them, RTN1 may serve as a potential biomarker for both UCEC and PCOS.

The clinicopathological and prognostic significances of EZH2 expression in urological cancers: A meta‑analysis and bioinformatics analysis.

The Drosophila zeste enhancer homolog 2 gene (enhancer of zeste homolog 2; EZH2) is an important member of the polycomb group (PcG) gene family, which maintains the homologous gene via chromosome modification during embryonic development. EZH2 is overexpressed in various tumors, is closely related to tumor formation and growth, and has a malignant phenotype that promotes tumor cell proliferation, proliferation and metastasis. In the present study, a meta- and bioinformatic analysis was performed using data from multiple online databases until August 30, 2022. EZH2 upregulation was found in kidney, bladder and prostate cancers. EZH2 expression was negatively related to TNM staging and pathological grade in kidney and prostate cancers (P<0.05), as well as invasion depth and pathological grade in bladder cancer. According to the KM-plotter database, EZH2 expression was inversely associated with poor overall survival in patients with kidney clear cell renal cell carcinoma (RCC) and papillary RCC and with favorable survival in bladder cancer. EZH2 expression was negatively related to relapse-free survival in kidney papillary RCC and bladder cancer but positively associated with kidney clear cell RCC. According to GEPIA and UALCAN databases, EZH2 expression was higher in tumor tissue than normal tissue. The TIMER database showed that EZH2 was closely associated with the proportion of seven immune cell infiltrates in kidney, bladder, and prostate cancers. High EZH2 expression may be a potential marker of tumorigenesis and metastasis in patients with urological cancers.

BASP1 expression is associated with poor prognosis and is correlated with immune infiltration in gastric cancer.

BASP1 is a membrane-bound protein that plays a promotional or inhibitory role in a variety of tumors; however, its role in gastric cancer (GC) and in the immune microenvironment has not been reported. The objectives of this study were to determine whether BASP1 is a valuable prognostic marker for GC and to explore its role in the immune microenvironment of GC. The expression level of BASP1 in GC was analyzed based on the TCGA dataset and further verified using GSE54129 and GSE161533 datasets, immunohistochemistry, and western blotting. The association between BASP1 and clinicopathological characteristics, as well as its predictive value, were examined using the STAD dataset. Cox regression analysis was performed to determine whether BASP1 can be used as an independent prognostic indicator for GC, and a nomogram was constructed to predict OS. The association between BASP1 and immune cell infiltration, immune checkpoints, and immune cell markers was confirmed by enrichment analysis, as well as analysis based on the TIMER and GEPIA databases. BASP1 was observed to be highly expressed in GC and was associated with a poor prognosis. The expression of BASP1 was positively correlated with the expression of immune checkpoints and immune cell markers, as well as immune cell infiltration. Thus, BASP1 may serve as a standalone prognostic indicator for GC. BASP1 is highly correlated with immune processes, and its expression is positively correlated with the degree of immune cell infiltration, immune checkpoints, and immune cell markers.

ASF1B, as an Independent Prognostic Biomarker, Correlates with Immune Infiltrates in Hepatocellular Carcinoma.

Hepatocellular Carcinoma (HCC) is one of the fastest-growing malignancies globally. The impact of surgical treatment is limited, and molecular targeted therapy has not yielded a consistent efficacy. This warrants for identification of novel molecular targets. The Anti- Silencing Function of 1B histone chaperone (ASF1B) was previously studied in numerous cancers. However, the understanding of its role in HCC is limited. The TIMER database was used to analyze the ASF1B expression in pan-cancer and paracarcinoma tissues. ASF1B expression in HCC was confirmed using the HCCDB database, Quantitative real-time PCR (q-PCR), and Western Blot (WB) assays. The relationship between clinicopathological parameters and ASF1B expression was analyzed using UALCAN, whereas the prognostic value of ASF1B was evaluated using the GEPIA database. Linkedomics and cBioPortal databases were used to validate the ASF1B co-expression associated with immune infiltration by the TIMER database. Moreover, cell proliferation after ASF1B-knockdown was determined through CCK8 and clone formation assays. ASF1B was highly expressed in HCC tissues, and the expression levels were linked to tumor grade, race, and disease stage. Univariate and multivariate Cox models showed that ASF1B is an independent prognostic factor in HCC. CCK8 and clone formation assays demonstrated that ASF1B promotes cell proliferation. Gene co-expression analysis in Linkedomics demonstrated that HJURP, KIF2C, KIF4A, KIF18B, and KIFC1 expressions were closely associated with ASF1B and immune infiltrate cells. This study shows that ASF1B promotes the proliferation of HCC. Besides, ASF1B could be a potential prognostic biomarker for HCC patients.

Comprehensive analysis of the expression and prognosis value of claudin family members in clear cell renal cell carcinoma

Objective: Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all renal cancers and has a poor prognosis. Studies have found that the abnormal expression of claudins (CLNDs) can influence the functions of tight junctions (TJs) and plays an important role in the occurrence, development, and metastasis of malignant tumours in a variety of epithelial malignant tumours. However, the roles of the different CLNDs in ccRCC are poorly understood. Methods: Used the GEPIA, UALCAN, HPA, Kaplan-Meier Plotter, cBioPortal, String-DB, GeneMANIA, Metascape, and TIMER databases to collect data. Results: The expression levels of CLDN7, 8, 10, 11, 14, 16, and 19 were significantly reduced and promoters were hypermethylated in ccRCC-affected tissues. ccRCC patients with low expression levels are associated highly with the clinical cancer stages, tumour grades, and poor overall survival. Protein interaction and enrichment analysis showed the differential expressions of CLDNs were primarily associated with epithelial cell differentiation and regulation of cell adhesion. Moreover, differential expressions of CLDNs were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells in ccRCC. Conclusion: They are expected to serve as biomarkers for predicting the prognosis of ccRCC patients.

Integrative Multi-Omics Analysis of Identified Ferroptosis-Marker RPL8 as a Candidate Oncogene Correlates with Poor Prognosis and Immune Infiltration in Liver Cancer.

Liver Hepatocellular Carcinoma (LIHC) is characterized by high malignancy, poor prognosis, and high recurrence rate worldwide. The role of ferroptosis in tumorigenesis and progression has been confirmed in previous studies. However, the multi-omics analysis in liver cancer of ferroptosis-markers RPL8 remains to be elucidated. In this analysis, the RPL8 mRNA expression was analyzed via the GEPIA, TIMER and UALCAN databases. In addition, we verified the mRNA expression of RPL8 by qRT-PCR experiment. The Kaplan-Meier plotter, UALCAN, TCGAportal and HPA databases were applied to evaluate RPL8 on prognosis and clinicopathological parameters. Moreover, we used TIMER and Kaplan-Meier plotter to analyze the correlation of RPL8 to immune cell infiltration and immune cell type markers to prognosis. In addition, networks and function enrichment between RPL8 coexpression genes were analyzed by GeneMANIA, cBioportal and Metascape databases. What's more, we used FerrDb and GEPIA databases to analyze the correlation of 23 Ferroptosis-related genes with RPL8. The mRNA expression of RPL8 was over-expressed in multiple cancers. In addition, transcription and translation levels of RPL8 in LIHC were significantly higher than normal tissues. Furthermore, higher expression of RPL8 was closely related to shorter OS in LIHC patients. The analysis of Kaplan-Meier plotter proved that RPL8 expression was related to stage, Sorafenib treatment, alcohol consumption and hepatitis virus. Moreover, the results showed that the methylation expression level of RPL8 was significantly associated with age, gender, grade, stage and TP53 mutation of LIHC. RPL8 and its co-expression genes were primarily involved in liver regeneration and immune system process. Immune infiltration analysis showed the RPL8 expression had positively correlated with immune cells and immune subtypes in LIHC. Furthermore, qRT-PCR experiment validated the expression difference of RPL8 in liver cancer. Our findings elucidated that ferroptosis-markers RPL8 may play an important role in prognosis, and significantly correlate with ferroptosis-related genes, it also revealed the potential of RPL8 as a novel therapeutic target for LIHC treatment and prognosis assessment.

Expression and clinical significance of PD-1 in UCEC and its Impact on tumor.

Programmed death 1 (PD-1) plays an important role in the immune escape, occurrence and development of tumors by inhibiting the function of immune cells. However, its prognostic value in uterine corpus endometrial carcinoma (UCEC) and its impact on the tumor microenvironment remain to be further explored. Transcriptional datasets were retrieved from the GEPIA, TIMER and TCGA databases. "edgeR" package was used for the identification of differentially expressed genes (DEGs) between two groups of patients (PD1-high and PD1-low group). Gene set enrichment analysis (GSEA) was performed to identify underlying pathways between betweenPD1-high and PD1-low groups functioning in UCEC. Gene Correlation Analysis was used to further confirm the associations of PD1 expression with T-cell-related genes. Cytoscape software was used to identify hub genes in DEGs. Kaplan-Meier analysis was performed to validate the prognostic value of hub genes. Mutational characteristics of UCEC patients according to PD1 levels were depicted and analyzed. We found that the transcriptional expression of the PD1 gene in UCEC tumor tissues markedly increased in cohorts from the GEPIA and TCGA databases. PD1 expression was negatively correlated with gene signatures associated with the T-cell receptor signaling pathway and primary immunodeficiency. GESA confirmed that PD1 expression was negatively correlated with gene signatures associated with the T-cell receptor signaling pathway. T-cell receptor complex-related genes, ZAP70, TRAC, CD3D, CD3E, CD8A, TRBC2, TRBV28 and CD247, showed significant positive associations with PD1 expression. The results of the Kaplan-Meier OS analysis indicated that PD1, TIGIT, FASLG, ICOS and TNFRSF9 are the protective factor for patients with UCEC. The top 5 genes of mutations in the low expression group, included PTEN (56%), PIK3CA (43%), TP53 (41%), TTN (39%), and ARID1A (37%). The genes with a higher proportion of mutations in the PD1-high group are PTEN (67%), TTN (62%), PIK3CA (53%), ARID1A (52%), and MUC16 (12%). The prognosis of UCEC patients with PD1 overexpression phenotype is worse than that of the PD1 low group, which is due to the involvement of the PD1 gene in the T-cell receptor signaling pathway. This study provides a further theoretical basis and reference for targeted therapy against PD1.

The relationship between the expression of amplified in breast cancer 1、androgen receptor and tamoxifen resistance in breast cancer

Objective: To discuss the value of amplified in breast cancer 1(AIB1) and androgen receptor (AR) for the resistance of adjuvant tamoxifen in estradiol receptor (ER) positive breast cancer. Methods: A total of 188 cases with breast cancer after receiving tamoxifen treatment in the Tianjin Medical University Cancer Institute and Hospital from June 2008 to July 2013 were enrolled in this study.Using immunohistochemical SP method to detect AIB1and AR expression in breast cancer tissue, analyzing the relationship of AIB1 and AR expression and the effect of tamoxifen.And verify the results of the experiment through the GEPIA database. Results: The response of tamoxifen was 80.3%. The response rate in AR positive group and AR negative group was 79.6% and 82.4%, with no significant difference (P=0.669). The response rate in AIB1 High expression group and AIB1 Low expression group was 68.4% and 93.3%, respectively, with a significant difference (P<0.001).The response rate in AR negative and AIB1 Low expression group, AR negative and AIB1 High expression group, AR positive and AIB1 Low expression group, AR positive and AIB1High expression group was 89.7%, 71.4%, 96.7%, 66.2%respectively, with a significant difference (P<0.001). Conclusions: The expression level of AIB1 is correlated with the therapeutic effect of tamoxifen in breast cancer. Its high expression can cause tamoxifen resistance, while AR positive and High expression of AIB1 are more likely to cause tamoxifen resistance, and AIB1 can be used as an independent influencing factor for breast cancer tamoxifentreatment.

Key genes involved with prognosis were identified in lung adenocarcinoma by integrated bioinformatics analysis

ObjectiveBy screening the core genes in lung adenocarcinoma (LUAD) with bioinformatics, our study evaluated its prognosis value and role in infiltration process of immune cells. MethodsUsing GEO database, we screened 5 gene chips, including GSE11072, GSE32863, GSE43458, GSE115002, and GSE116959. Then, we obtained the corresponding differentially expressed genes by analyzed 5 gene chips online by GEO2R (P < 0.05, |logFC| > 1). Then, through DAVID online platform, Cytoscape 3.6.1 software and PPI network analysis, the network was visualized and obtain the final core genes. Next, we plan to use the GEPIA, UALCAN, Kaplan–Meier plotter and Time 2.0 database for corresponding analysis. The GEPIA database was used to verify the expression of core genes in LUAD and normal lung tissues, and survival analysis was used to evaluate the value of core genes in the prognosis of LUAD patients. UALCAN was used to verify the expression of the LUAD core gene and promoter methylation status, and the predictive value of core genes was evaluated in LUAD patients by the Kaplan–Meier plotter online tool. Then, we used the Time 2.0 database to identify the relationship to immune infiltration in LUAD. Finally, we used the human protein atlas (HPA) database for online immunohistochemical analysis of the expressed proteins. ResultsThe expression of CCNB2 and CDC20 in LUAD were higher than those in normal lung tissues, their increased expression was negatively correlated with the overall survival rate of LUAD, and they were involved in cell cycle signal transduction, oocyte meiosis signal transduction as well as the infiltration process of immune cells in LUAD. The expression proteins of CCNB2 and CDC20 were also different in lung cancer tissue and normal lung tissue. Therefore, CCNB2 and CDC20 were identified as the vital core genes. ConclusionCCNB2 and CDC20 are essential genes that may constitute prognostic biomarkers in LUAD, they also participate the immune infiltration process and protein expression process of LUAD, and might provides basis for clinical anti-tumor drug research.