Kaplan-Meier Plotter Research Articles

A Comprehensive Pan-Cancer Analysis Identified that TRIB3 was Associated with Immune Cell Infiltration and Poor Prognosis.

Previous studies have demonstrated that TRIB3 plays a carcinogenic role in tumor progression. However, the exploration of TRIB3 at the pan-cancer level has not been reported. This study aimed to conduct a comprehensive pan-cancer analysis of TRIB3. We explored the expression pattern and functional mechanism of TRIB3 on the basis of multiple databases. We first explored the expression level of TRIB3 in the TCGA database. Then, the receiver operation characteristic curve (ROC), Kaplan-Meier plotter, and Cox regression were used to estimate the diagnostic and prognostic value of TRIB3, respectively. We also explored the relationship between TRIB3 and the infiltration of tumor immune cells, as well as the expression of immune checkpoint molecules. Gene enrichment and protein interaction network analysis were carried out to identify possible carcinogenic molecular mechanisms and functional pathways. Finally, we compared the non-promoter region methylation of TRIB3 in normal and tumor tissues and explored potential systems with unique functions in TRIB3-mediated tumorigenesis. The expression level of TRIB3 was elevated in multiple tumor types, and the high expression of TRIB3 was associated with poor prognosis. TRIB3 had a higher frequency of genetic changes in several tumors and showed varying trends in TRIB3 methylation levels. Additionally, high expression of TRIB3 was also associated with infiltration of cancer-related fibroblasts and different types of immune cells and was positively correlated with the expression of immune checkpoint molecules. Furthermore, gene enrichment analysis suggested that TRIB3 may play a role in the malignant progression of cancer by participating in protein post-translational modifications and activating transcription initiation factors. Our pan-cancer analysis provided the potential carcinogenic role of TRIB3 in tumors and verified a promising target for clinical immune treatment.

TOB1 inhibits the gastric cancer progression by focal adhesion pathway and ERK pathway based on transcriptional and metabolic sequencing

Gastric cancer is one of the most malignant digestive tract tumors worldwide and its progression is associated with gene expression and metabolic alteration. We revealed that the gastric cancer patients with lower expression level of TOB1 exhibited poorer overall survivals according to the data in Kaplan–Meier Plotter. The unphosphorylated TOB1 protein which is effective expressed lower in gastric cancer cells. The gastric cancer cells with TOB1 gene depletion performed higher abilities of proliferation, migration and invasion and lower ability of apoptosis in vitro. The TOB1 gene depletion also promoted the tumorigenesis of gastric cancer cells in vivo. The gastric cancer cells with TOB1 gene overexpression had the converse behaviors. The transcriptional and metabolic sequencing was performed. The analyzation results showed that genes correlate-expressed with TOB1 gene were enriched in the pathways related to ERK pathway, including focal adhesion pathway, which was verified using real-time quantitative PCR. After inhibiting ERK pathway, the proliferation, colony formation and migration abilities were reduced in gastric cancer cells with low phosphorylated TOB1 protein expression level. Moreover, Pearson correlation analysis was adopted to further analyze the correlation of enriched metabolic products and differentially expressed genes. The expression of Choline, UDP-N-acetylglucosamine, Adenosine and GMP were related to the function of TOB1. This study demonstrates the genes and metabolites related to focal adhesion pathway and ERK pathway are the potential diagnosis and therapeutic targets to gastric cancer with TOB1 depletion.

Double-negative T cells with a distinct transcriptomic profile are abundant in the peripheral blood of patients with breast cancer.

Double-negative T (DNT) cells comprise a distinct subset of T lymphocytes that have been implicated in immune responses. The aim of this study was to characterize the peripheral DNT population in breast cancer (BC) patients. DNT cells were isolated from the peripheral blood samples of BC patients and healthy controls by flow cytometry. The sorted DNT cells were analyzed by the Smart-seq2 for single-cell full-length transcriptome profiling. The differentially expressed genes (DEGs) between the BC and control groups were screened and functionally annotated by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using R. The protein-protein interaction (PPI) network of the DEGs was constructed using the CytoHubba and MCODE plug-in of Cytoscape software to identify the core genes. Survival status, DNA methylation level, immune infiltration and immune checkpoint expression were analyzed using Kaplan-Meier Plotter, UALCAN, MethSeuvr, TIMER, and TISIDB respectively. The sequencing results were verified by RT-qPCR. The percentage of DNT cells was higher in the BC patients compared to healthy controls. We identified 289 DEGs between the DNT populations of both groups. GO and KEGG pathway analyses revealed that the DEGs were mainly related to immunoglobulin mediated immune response, complement activation, and B cell receptor signaling. The PPI networks of the common DEGs were constructed using Cytoscape, and 10 core genes were identified, including TMEM176B, C1QB, C1QC, RASD2, and IFIT3. The expression levels of these genes correlated with the prognosis and immune infiltration in BC patients, and were validated by RT-qPCR (P < 0.05). DNT cells are abundant in patients with BC, and might exert anti-tumor immune responses by regulating genes such as TMEM176B and EGR1.

Identification of RTP4 facilitating ovarian cancer by bioinformatics analysis and experimental validation.

Ovarian cancer (OV) is the most malignant gynecological tumor in women, with poor prognosis and high mortality rate. This study aims to identify hub genes in OV and explore the role of Receptor transporter 4 (RTP4) in OV progression. Common differentially expressed genes (DEGs) were screened from two microarray datasets. GO and KEGG enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed by STING. Kaplan-Meier plotter was used to analyze prognosis. The effect of target gene on immune infiltration was analyzed by TIMER. The proliferation, migration, and invasion of OV cells were measured by CCK-8, wound healing assay, and trans-well assay, respectively. A total of 293 common DEGs were selected from GSE12470 and GSE16709 datasets. Hub genes, EPCAM, KIFC1, RTP4, TAGLN, and ZFP36 were selected by PPI network. Kaplan-Meier plotter demonstrated that high expression of RTP4 was related to low overall survival in OV patients. The TIMER result showed that high expression of RTP4 promoted immune infiltration of CD8+ T cells, B cells, neutrophils, and dendritic cells in OV. Moreover, silencing RTP4 significantly inhibited the proliferation, migration, and invasion of OV cells. RTP4 was associated with the poor prognosis in OV. In summary, silencing RTP4 inhibited the proliferation, migration, and invasion of OV cells, having the potential to be a novel therapeutic target for OV.

Identification of biomarker associated with Trop2 in breast cancer: implication for targeted therapy

PurposeTrop2, a cell membrane glycoprotein, is overexpressed in almost all epithelial cancers. This study aimed to explore the mutational characteristics and significance of Trop2 in breast cancer (BC).MethodsPatients diagnosed with BC (n = 77) were enrolled to investigate expression level and clinical characteristics of Trop2. Database of cBioPortal and Kaplan–Meier Plotter were used to evaluate the effects of Trop2 (TACSTD2) genomic ateration and mRNA expression levels on disease-free survival (DFS) and relapse-free survival (RFS), respectively. Based on next generation sequencing analysis, the Trop2 mutation characteristics of BC patients were deeply depicted. In addition, Trop2 expression, mutation and methylation signature associated with Trop2 mutations were analyzed.ResultsTrop2 mutation and high expression of Trop2 were predictive biomarker for shorter DFS and RFS in BC. The positive rate of Trop2 expression in these 77 BC patients was 96.1% (74/77). Based on the Trop2 expression level, the patients were classified into Trop2 negative group, medium expression group and high expression group. The mutation frequencies of MAP3K1, NOTCH2, PTEN and MAGI2 were significantly higher in Trop2 medium expression group than high expression group. Moreover, we investigated the effect of the Trop2 mutations on other genes, including co-expressed genes, differentially mutated genes, differentially expressed genes, gene methylation and phosphorylation. We found that MED8, DPH2, KDM4A, EBNA1BP2, USP1, IPO13, CGAS, PRKAA2, NCOA7, ASCC3 and ABRACL were differentially expressed, mutated and methylated between Trop2 mutation group and wild group.ConclusionMAP3K1, NOTCH2, PTEN and MAGI2 mutations were significantly different between Trop2 medium expression and Trop2 high expression BC patients. The effects of Trop2 mutation on the expression, variation, methylation, and phosphorylation of other genes were comprehensively revealed. High expression level of Trop2 and Trop2 mutation were predictive biomarker for poor prognosis and targeted therapy in BC.

Expression Profile and Prognostic Values of IRX Family Members in Lung Adenocarcinoma.

The potential role of the iroquois homeobox (IRX) genes in tumorigenesis is a subject of interest, yet their specific involvement in lung adenocarcinoma (LUAD) has not been extensively examined. This research endeavored to explore the impact of the IRX genes on the onset and progression of LUAD. Utilizing data from The Cancer Genome Atlas (TCGA), samples of LUAD were selected for analysis. The influence of the IRX genes was scrutinized through various tools, including Kaplan-Meier Plotter, cBioPortal, and the R programming language (version 3.6.3), with gene expression levels being confirmed in cellular models via quantitative real-time polymerase chain reaction (qRT-PCR). It was observed that the levels of IRX1/2/3/6 were notably diminished in LUAD tissues when juxtaposed with healthy lung tissue. Conversely, the expression of IRX4 was found to be elevated in LUAD. Correlations were identified between IRX gene expression and several clinical parameters such as T stage, smoking history quantified in pack-years, lymph node involvement, patient gender, initial treatment responses, and smoking status. The diminished expression of IRX2/5 emerged as a significant indicator of an unfavorable prognosis in LUAD. The study also highlighted the potential of various IRX genes as diagnostic indicators for LUAD. These genes were implicated in the facilitation of LUAD's growth and spread through a range of biological pathways, encompassing the Ras signaling and more. Additionally, a pronounced link was discovered between the infiltration of immune cells and the expression patterns of the IRX genes. IRX genes were abnormally expressed in LUAD cell lines. IRX gene family could serve not only as indicators of LUAD prognosis but also as therapeutic targets for LUAD.

CD25+FOXP3+CD45RA− regulatory T-cell infiltration as a prognostic biomarker for endometrial carcinoma

BackgroundRegulatory T (Treg) cells reportedly play crucial roles in tumor angiogenesis as well as antitumor immunity. In order to explore their therapeutic potential, we investigated the precise prognostic impact of Treg markers in endometrial carcinoma.MethodsWe performed multiplexed immunofluorescence and quantitative image analyses of CD25, FOXP3, CTLA4, and CD45RA in tumor specimens from 176 consecutive patients treated at our institution for primary endometrial carcinomas. Bioinformatics analyses were further conducted to corroborate the findings.ResultsHigh CD25+, FOXP3+, and CD25+FOXP3+CD45RA− stromal cell counts correlated with better overall survival (OS) (p = 0.00019, 0.028 and 0.0012) and MSI-high (p = 0.015, 0.016 and 0.047). High CD45RA+ stromal cell count was associated with superficial myometrial invasion (p = 0.0038). Bioinformatics survival analysis by Kaplan-Meier plotter showed that high CD25, FOXP3, CTLA4, and CD45RA mRNA expressions correlated with better OS (p = 0.046, 0.00042, 0.000044, and 0.0022). Univariate and multivariate analyses with various clinicopathologic prognostic factors indicated that high CD25+ or CD25+FOXP3+CD45RA− stromal cell count was significant and independent for favorable OS (p = 0.0053 and 0.0015). We subsequently analyzed the correlations between the multiplexed immunofluorescence results and treatment-free interval (TFI) after primary chemotherapy in recurrent cases, finding no significant associations. Further analysis revealed that high ratio of CD25+ : CD8+ cell count or CD25+FOXP3+CD45RA− : CD8+ cell count correlated with longer TFI (p = 0.021 and 0.021).ConclusionThe current observations suggest that the balance between CD25+ or CD25+FOXP3+CD45RA− cells and CD8+ cells, corresponding to promoting or inhibiting effect on tumor angiogenesis, affect tumor chemosensitivity leading to prognostic significance. CD25+FOXP3+CD45RA− effector Treg tumor infiltration may serve as a useful prognostic biomarker and a potential target for immunotherapeutic manipulation of tumor chemosensitivity by novel management for advanced/recurrent endometrial carcinomas.

SEMA7A as a Novel Prognostic Biomarker and Its Correlation with Immune Infiltrates in Breast Cancer.

The role of Semaphorin 7a (SEMA7A) in the initiation and progression of different types of cancerous lesions has been extensively studied. However, the prognostic significance of SEMA7A, specifically in breast cancer (BC), lacks clarity. We conducted an evaluation on the relationship between SEMA7A and the prognosis, immune invasion and tumor mutation burden in different types of cancer by analyzing data from The Cancer Genome Atlas database. The present study focused on investigating the expression level, mutation, immune correlation and coexpression of SEMA7A in BC, utilizing various databases such as the University of Alabama at Birmingham Cancer data analysis portal, cBioPortal and tumor immune estimation resource. Survival analysis was carried out using the Kaplan-Meier Plotter. Furthermore, we employed the R software package to generate receiver operating characteristic (ROC) curves and nomograms. Notably, P<0.05 was considered to indicate statistical significance. Using pancancer analysis, it has been observed that the expression of SEMA7A is elevated in various types of cancer and is strongly correlated with the prognosis of different cancer types. SEMA7A also exhibits a significant association with the tumor mutation burden of diverse types of cancer. Moreover, SEMA7A displays a notable increase in BC cases, and was indicated to have a substantial association with the abundance of immune infiltration. In-depth survival analysis demonstrated that elevated levels of SEMA7A expression are notably linked to shorter overall survival and distant metastasis-free survival among patients with BC. The efficiency of SEMA7A as a reliable prognostic biomarker for BC has been substantiated by the validation of ROC curves and nomograms. SEMA7A has the potential to function as a prognostic indicator for BC, and its correlation with immune infiltration in BC is significant.

Prognostic biomarkers based on GUF1, EFTUD2 and GSPT1 targets affecting migration of gastric cancer cells.

Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a protein coding gene which is involved in tumor development and progression in several types of human cancer, but little is known about the function of eEF1A2 proteins in gastric cancer (GC). This study aimed to investigate the effects of GUF1, EFTUD2 and GSPT1 on the migration of GC cells. The Oncomine and The Cancer Genome Atlas (TCGA) databases were used to evaluate the expression of GUF1, EFTUD2, GSPT1 and GSPT2 in GC and the association of eEF1A2 family with individual clinical characteristics. Kaplan-Meier (K-M) Plotter hinted the prognostic value of GUF1, EFTUD2, GSPT1 and GSPT2. GSE62254 and GSE66222 datasets were used to validate the expression of GUF1, EFTUD2, GSPT1. AGS cell line and GES line were also used for validating the function of GUF1, EFTUD2, GSPT1. RNA interference (RNAi) of GUF1, EFTUD2 and GSPT1 had been used to query those genes expression pattern and dissect the proliferation and migration in GC cell lines. GUF1, EFTUD2 and GSPT1 were significantly up-regulated in GC cell lines. High expression of GUF1, EFTUD2 and GSPT1 was correlated with cell proliferation and migration induced in GC cells. GUF1, EFTUD2 and GSPT1 may be potential novel oncogenes that helps to maintain the survival of GC cells. This study identified that high levels of GUF1, EFTUD2 and GSPT1 expression are predictive biomarkers for a poor prognosis in GC.

Putative Dual Roles of Bone Morphogenetic Protein 8B (BMP8B) in Disease Progression of Gastric Cancer.

Increased expression of bone morphogenetic protein 8B (BMP8B) in bone marrow and primary tumors of patients with gastric cancer (GC) is associated with disease progression and poor prognosis. However, a reduced expression has also been seen in GCs due to histone acetylation. This study aimed to evaluate BMP8B transcript levels in a large GC cohort and its impact on cellular functions. BMP8B transcripts were determined in 319 gastric tumors and compared with 182 adjacent normal tissues using real time PCR, with a further analysis conducted in the TCGA database. Kaplan-Meier plotter analysis was performed to evaluate the correlation between BMP8B and prognosis of the disease. BMP8B knockdown model was employed to determine the effect of BMP8B on the function of GC cells (HGC27). BMP8B mRNA levels were significantly up-regulated in the GC tissues compared with adjacent normal tissues in both TCGA database and our own database from Beijing Cancer Hospital, and high BMP8B expression was associated with poor prognosis. BMP8B is most likely to be involved in the differentiation of GC. Poorly differentiated GC samples presented a significantly reduced BMP8B expression in relation to well-differentiated and moderately differentiated GC. BMP8B knockdown inhibited proliferation of GC cells, while promoted invasion and migration of cancer cells. BMP8B was reduced in GCs, whereas higher BMP8B expression was associated with poor prognosis. BMP8B knockdown inhibited proliferation of GC cells, and promoted invasion and migration. Our results suggest that BMP8B plays dual roles in GC.

Gliomedin drives gastric cancer cell proliferation and migration, correlating with a poor prognosis

Gastric cancer (GC) is a prevalent global malignancy, often diagnosed at advanced stage due to a lack of early symptoms and reliable markers. Previous research has identified gliomedin (GLDN) as a potential predictive marker for poor prognosis in cancer patients. However, the specific relationship between GLDN expression and GC prognosis has been unclear. Using the Tumor-Immune System Interaction Database (TISIDB), we examined GLDN expression in GC tissues and found a positive correlation with advanced clinical stages. Kaplan-Meier Plotter analysis further demonstrated that elevated GLDN levels were closely associated with poor prognosis in GC patients. To explore the functional significance of GLDN in GC, we conducted experiments involving GLDN overexpression and knockdown in GC cell lines, as well as subcutaneous tumor formation in nude mice. Our findings provided compelling evidence that GLDN promotes GC cell proliferation, viability, and migration, significantly enhancing tumor growth in vivo. Mechanistically, RNA-sequencing (RNA-seq) combined with bioinformatics analysis revealed that GLDN influences genes enriched in the p53 signaling pathway. Our data suggest that GLDN likely regulates cell proliferation through the p53-p21-CyclinD/CDK4 signaling axis. In conclusion, our study underscores GLDN's critical role in regulating GC cell proliferation and migration, and proposes its potential as a prognostic marker for GC patients.

BUB1 as a novel marker for predicting the immunotherapy efficacy and prognosis of breast cancer.

Budding uninhibited by benzimidazole 1 (BUB1) is a highly conserved serine/threonine kinase, showing prominent importance for proper function during mitosis. However, little is known about BUB1 mRNA expression in breast cancer (BRCA) and its correlation with prognosis and immune infiltration. Hence, we aimed to unveil its potential as groundbreaking biomarkers for immunotherapy efficacy and the prognosis of BRCA. Database for Annotation, Visualization, and Integrated Discovery (DAVID) is a potent tool for identifying significant clusters of genes and pathways in the resulting dataset. In this study, gene set enrichment analysis of BUB1 was conducted using DAVID. The clinical characteristics of patients with or without altered BUB1 mRNA expression were compared using cBioPortal. Tumor Immune Estimation Resource (TIMER) is a known as database for comprehensive analysis of tumor-infiltrating immune cells in various cancers. In the present study, the relationship between BUB1 expression and the abundance of immune infiltrates was explored using TIMER in BRCA. Immunohistochemistry staining was performed to analyze the protein expression of BUB1 in tumor tissue specimens. We used PrognoScan and Kaplan-Meier Plotter to evaluate the prognosis of patients with different BUB1 expression levels. The expression of BUB1 in various tumor tissues was higher than that in adjacent normal tissues. BUB1 was mainly localized to the nucleoplasm and additionally localized to the cytosol. Functional enrichment analyses revealed that the cell cycle was the most significant pathway. Abnormal BUB1 mRNA expression was more frequently detected in invasive ductal carcinoma with higher histological grades and BRCAs with estrogen receptor (ER)-negative, human epidermal growth receptor 2 (HER2)-negative, and basal-like phenotypes. The BUB1 expression was correlated positively with tumor purity, B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells, while BUB1 had no significant correlation with macrophages. The results of immunohistochemical staining from clinical samples further confirmed that BUB1 was overexpressed in BRCA compared to benign tumor (fibroadenoma of breast) (P<0.01). BRCA patients with lower BUB1 expression had a better prognosis than those with higher BUB1 expression in overall survival (OS) curves, distant metastasis-free survival (DMFS) curves, and relapse-free survival (RFS) curves (P<0.05). Our results suggest that BUB1 is a potential molecular biomarker for evaluating the prognosis and predicting the effectiveness of immunotherapy for BRCA.

Unveiling the role of RARs in stomach adenocarcinoma: clinical implications and prognostic biomarkers.

Retinoic acid receptors (RARs) family are known to play a significant role in the occurrence and development of tumors. However, the relationship between RARs and stomach adenocarcinoma (STAD) has not yet been clearly identified. The aim of this study is to evaluate the expression profile and clinical value of the RARs family in STAD. The expression level, clinical characteristics, prognostic value, immunity-related evaluations, genetic alteration and methylation site of RARs in STAD were explored using a series of online databases including gene expression profiling interactive analysis (GEPIA), tumor immune estimation resource (TIMER), University of Alabama at Birmingham cancer data (UALCAN), Human Protein Atlas (HPA), Kaplan-Meier plotter, gene set cancer analysis (GSCA), cBioPortal, MethSurv, GeneMANIA, LinkedOmics, Metascape, Search tool for the retrieval of interacting genes (STRING), tumor immune single-cell hub (TISCH) and cancer cell line encyclopedia (CCLE). We discovered dramatically increased expression of RARA and decreased expression of RARB in STAD tissues, and many clinical variables were closely related to RARs. Notably, higher expressions of RARA and RARB as well as lower expression of RARG correlated with worse overall survival (OS) for STAD patients. The clinical value of prognostic model indicated that RARs were identified to be potential prognostic biomarkers for STAD patients. Moreover, RARB was closely related to immune cell infiltration, which had effect on the role of RARB in STAD prognosis. And the genetic alteration of RARB was significantly associated with the longer disease-free survival (DFS) of STAD patients. Additionally, some CpG sites of the RARs family were related with the prognosis of STAD patients. Functional enrichment analyses indicated that several pathways in STAD might be pivotal pathways regulated by RARs. At the single-cell level, there was some extent of infiltration of tumor microenvironment-related cells in the RARs expression in STAD. Our results evaluated the expression profile and clinical values of RARs in patients with STAD, which provided a basis for future in-depth exploration of the specific mechanisms of each member of RARs in STAD.

Unraveling the potential effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on the Protein structure and function of the human SLC30A8 gene on type 2 diabetes and colorectal cancer: An In silico approach

Background and aimsThe single nucleotide polymorphisms (SNPs) in SLC30A8 gene have been recognized as contributing to type 2 diabetes (T2D) susceptibility and colorectal cancer. This study aims to predict the structural stability, and functional impacts on variations in non-synonymous SNPs (nsSNPs) in the human SLC30A8 gene using various computational techniques. Materials and methodsSeveral in silico tools, including SIFT, Predict-SNP, SNPs&GO, MAPP, SNAP2, PhD-SNP, PANTHER, PolyPhen-1,PolyPhen-2, I-Mutant 2.0, and MUpro, have been used in our study. ResultsAfter data analysis, out of 336 missenses, the eight nsSNPs, namely R138Q, I141N, W136G, I349N, L303R, E140A, W306C, and L308Q, were discovered by ConSurf to be in highly conserved regions, which could affect the stability of their proteins. Project HOPE determines any significant molecular effects on the structure and function of eight mutated proteins and the three-dimensional (3D) structures of these proteins. The two pharmacologically significant compounds, Luzonoid B and Roseoside demonstrate strong binding affinity to the mutant proteins, and they are more efficient in inhibiting them than the typical SLC30A8 protein using Autodock Vina and Chimera. Increased binding affinity to mutant SLC30A8 proteins has been determined not to influence drug resistance. Ultimately, the Kaplan-Meier plotter study revealed that alterations in SLC30A8 gene expression notably affect the survival rates of patients with various cancer types. ConclusionFinally, the study found eight highly deleterious missense nsSNPs in the SLC30A8 gene that can be helpful for further proteomic and genomic studies for T2D and colorectal cancer diagnosis. These findings also pave the way for personalized treatments using biomarkers and more effective healthcare strategies.

TESC associated with poor prognosis enhances cancer stemness and migratory properties in liver cancer

Liver cancer stem cells (LCSCs) are responsible for recurrence, metastasis, and drug resistance in liver cancer. However, the genes responsible for inducing LCSCs have not been fully identified. Based on our previous study, we found that tescalcin (TESC), a calcium-binding EF hand protein that plays a crucial role in chromatin remodeling, transcriptional regulation, and epigenetic modifications, was up-regulated in LCSCs of spheroid cultures. By searching the Cancer Genome Atlas, International Cancer Genome Consortium, Human Protein Atlas, and Kaplan–Meier Plotter databases, we found that TESC expression was significantly elevated in liver cancer compared with that in normal liver tissue and was predictive of a decreased overall survival rate. Multivariate Cox analysis revealed TESC to be an independent prognostic factor for survival. High TESC expression was positively associated with cancer stem cell pathways, cancer stem cell surface markers, stemness transcription factors, epithelial–mesenchymal transition (EMT) factors, immune checkpoint proteins, and various cancer-related biological processes in liver cancer. Furthermore, TESC was implicated as promoting cancer stem cell properties through its influence on EMT. We demonstrated that TESC is a novel stemness-related gene that can serve as an independent prognostic factor for liver cancer.

ADCY5 act as a putative tumor suppressor in glioblastoma: An integrated analysis

BackgroundAdenylyl cyclase (AC) isoforms played a key role in the multiple cancer pathology, However, the expression, prognostic value and function of ADCY5 in Glioblastoma (GBM) have not been reported yet. This research intends to discover the expression, epigenetic alteration and biological function of ADCY5 in GBM and its value on patients' prognosis. Methods① Transcriptional level, epigenetic alteration, prognostic value and molecular network of ADCY5 were analyzed by using of public online datasets. ② The mRNA expression profile of ADCY5 was explored by using GEPIA database and protein expression levels were detected by HPA Database. ③ The prognostic value of ADCY5 was determined by Kaplan-Meier Plotter, GEPIA and CGGA database. ④ The epigenetic characteristics of ADCY5 were determined by DiseaseMeth database. ⑤ Identification of genes co-expressed with ADCY5 and potential mechanism analyses were performed by using DAVID cBioPorta and STRING. ⑥ Reverse transcription-polymerase chain reaction (RT-PCR), cell counting kit-8 (CCK-8), colony formation, wound-healing scratch and transwell assay were applied to detect relative mRNA expression and biological function of ADCY5 in GMB cells. ResultsADCY5 mRNA and protein were downregulated in GBM compared with normal tissues. Analysis of the genetics and epigenetics of ADCY5 suggested that its expression was negatively correlated with DNA methylation. High expression of ADCY5 was significantly associated with age, grade, IDH mutation, 1p19q_codeletion, radiotherapy and chemotherapy and acted as an independent prognostic factor in GBM. ADCY5 mRNA also down-expressed in GBM cell lines and re-expressed of ADCY5 could inhibit cell proliferation, viability, migration/invasion and epithelial-mesenchymal transition (EMT) in vitro. In the analysis of genes co-expressed with ADCY5, we found that cAMP/AKT pathway, cGMP-PKG pathway, Wnts pathway were dissimilarly enriched. ConclusionOur study indicated that ADCY5 could act as an epigenetic biomarker in GBM, as well as a prognosis target in patients with GBM.

Identification of differentially expressed genes and screening for key genes involved in ovarian cancer prognosis: An integrated bioinformatics and network analysis approach

Objectives: Ovaries are important and essential organs of animals in producing and releasing eggs. Ovarian cancer (OvCa) is one of the most prevalent lethal gynecological malignancies with a lack of distinct biomarkers. Advances in high-throughput genomic data and the continued refinement of bioinformatics tools enable the identification of potential biomarkers. Leveraging these insights, we can employ systems biology approaches to enhance the accuracy of diagnosis and prognosis. Material and Methods: A comparative analysis was conducted between normal and tumor samples, employing bioinformatics software and tools. Differential expression analysis utilized fold-change statistics, while DAVID 6.8 software was used to perform gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The protein-protein interaction (PPI) network was constructed differentially expressed genes (DEGs) using Search Tool for the Retrieval of Interacting Genes database, and Cytoscape 3.9.1, along with its Molecular Complex Detection and CytoHubba plugins, facilitated network visualization, analysis, and module detection. Hub gene expression and overall survival were explored through the Kaplan–Meier plotter, while Gene Expression Profiling Interactive Analysis 2 analyzed the tumor stage of OvCa patients. Hub genes protein expression was analyzed using the human protein atlas database through immunostaining results. The NetworkAnalyst program and Cytoscape were employed to analyze and visualize the transcription factor-hub gene associations. Subsequently, single-nucleotide variation, methylation, and pathway activity of hub genes were examined. Validation of hub genes messenger RNA expression was done using quantitative real-time polymerase chain reaction analysis. Results: 607 DEGs, including 248 upregulated and 359 downregulated genes, were identified. The top 20 candidate genes were screened out through PPI network analysis. We discovered that the genes BUB1 Mitotic Checkpoint Serine/Threonine Kinase B (BUB1B), Cyclin A2 (CCNA2), Mitotic Arrest Deficient 2 Like 1 (MAD2L1), Protein Regulator of Cytokinesis 1 (PRC1), Thyroid Hormone Receptor Interactor 13 (TRIP13), and ZW10 Interacting Kinetochore Protein (ZWINT) exhibited significant importance in OvCa prognosis. Conclusion: Six genes, BUB1B, CCNA2, MAD2L1, PRC1, TRIP13, and ZWINT (identified as functional hub genes), are probably playing tumor-promotive roles, except TRIP13. All genes product is functionally related to the cell cycle. These can be targeted in quest of potential therapeutics for OvCa treatment.

Expression and clinical significance of CLDN7 and its immune-related cells in breast cancer

BackgroundCLDN is a core component of tight junctions (TJs). Abnormal expressions of CLDNs are commonly detected in various types of tumors. CLDNs are of interest as a potential therapeutic target. CLDNs are closely associated with most cancers of epithelial origin, especially when CLDN7 promotes cancer cell metastasis, such as in gastric, cervical, and ovarian cancers.Its expression and prognosis in breast cancer (BC) remain unknown.The purpose of this study was to investigate the expression pattern of CLDN7 and related immune factors in BC and shed light on a better therapeutic avenue for BC patients.MethodThe cBioPortal, GEPIA, and TCGA databases were used to comprehensively assess the expression of CLDN7 in BC. The Kaplan-Meier Plotter (KMP) database was applied to examine the relationship among the CLDN7 overexpression (OE), prognosis, and overall survival (OS) of BC patients. Immunohistochemical staining was performed on 92 BC tissue samples and 20 benign breast tumors to verify the expression level of CLDN-7 protein and its correlation with clinicopathological features and prognosis. TIMER2.0 was used to analyze the correlation between the CLDN7 OE and immune gene activation using BC-related transcriptomic data. Enrichment analyses of CLDN7-related immune pathways were conducted using online databases. The risk of expression of CLDN7-related immune genes was assessed and differentially expressed (DE) genes were included in the construction of the risk prognosis nomogram.ResultsBoth database analysis and clinical sample validation results showed that CLDN7 was significantly overexpressed (OE) in BC, and the OE was correlated with poor DFS in BC patients (p < 0.05). TIMER2.0 analysis indicated that CLDN7 OE was negatively associated with the activation of B-cells, CD4+ T-cells, and CD8+ T-cells but positively with the M0 macrophages. Pathway enrichment analysis suggested that CLDN7-related immune factors were mostly involved in the NF-κB and T-cell receptor (TCR) signaling pathways. Univariate Cox regression was used to analyze the correlation between 52 CLDN7 related genes and OS, and 22 genes that are related to prognosis were identified. Prognostic genes were included in the prognostic nomogram of BC with a C-index of 0.76 to predict the 3-year and 5-year OS probabilities of BC individuals.ConclusionsThese findings provide evidence for the role of CLDN7-linked tumor immunity, suggesting that CLDN7 might be a potential immunotherapeutic target for BC, and its association with immune markers could shed light on the better prognosis of BC.

Pan-Cancer Analysis Reveals Long Non-coding RNA (lncRNA) Embryonic Stem Cell-Related Gene (ESRG) as a Promising Diagnostic and Prognostic Biomarker.

Embryonic stem cell-related gene (ESRG; also known as HESRG) is a long non-coding RNA (lncRNA). It is involved in the regulation of human pluripotent stem cells (hPSCs) self-renewal. ESRG gene has the ability to interact with chromatins, different RNA types, and RNA binding proteins (RBP); thus making ESRG be considered an oncogenic lncRNA, where its expression is detected in various tumor tissues. This study aimed to evaluate the prospective diagnostic and prognostic values of ESRG in various human cancers. The expression of ESRG in various cancers was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) databases. Moreover, the correlation between the expression of ESRG and clinical pathological parameters was analyzed using UALCAN. The effect of ESRG expression on the survival outcome was evaluated using Kaplan-Meier plotter, UALCAN, GEPIA, and TIMER. The correlation between ESRG expression and immune cell infiltration was studied by TIMER. Additionally, the genetic alterations were investigated cBioportal. Our findings were validated using the GEO2R database. Our results showed ESRG to be significantly up-regulated incolon adenocarcinoma (COAD) and lung squamous cell carcinoma (LUSC) with p<0.001, in addition to rectum adenocarcinoma (READ), and uterine carcinosarcoma (UCEC) withp<0.01. Regarding pathogenic stages, there was a significant upregulation in stages 2, 3, and 4 compared to normal in COAD and stages 1, 2, and 3 for LUSC patients. The combined prognostic analysis showed that the up-regulated expression of ESRG was associated with better survival outcomes in patients with brain lower-grade glioma (LGG). Our results demonstrate a significant negative correlation between ESRG expression and the abundance of CD8+T cells in COAD, READ, LUSC, and UCEC. Additionally, ESRG was mutated in 0.77 (<1%) of the queried samples, and the most prevalent ESRG mutations are deep deletion mutations, followed by amplification. Analysis of ESRG across various cancer types elucidated its potential to be used as a diagnostic biomarker in COAD, LUSC, READ, and UCEC and a promising prognostic biomarker in LGG. Our findings provide useful insights for future research.

Clinical Significance and Potential Function of Complement Factor D in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by aggressive proliferation and a poor prognosis. The objective of this study is to elucidate the specific role of complement factor D (CFD) in AML, with the aim of identifying robust prognostic markers for the disease. We performed a systematic investigation on clinical significance and potential function of CFD in AML by using the R Programming Language with The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The Human Protein Atlas (HPA), The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, Cancer Cell Line Encyclopedia (CCLE) database, and Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer (CAMOIP) database. The expression of CFD in AML patients was verified by reverse transcription-quantitative polymerase chain reaction(RT-qPCR). The expression of CFD was the highest in AML cells than in other tumor cell lines. The expression of CFD was also higher in AML patients than in the matched normal group. Compared with the low expression of the CFD group, high expression of CFD predicted better overall survival (OS) and lower tumor mutational burden (TMB) in AML patients. Moreover, a nomogram model based on CFD was successfully constructed to predict the OS of AML patients. Notably, the expression of CFD was associated with drug sensitivity and monocyte cell infiltration. CFD could serve as a potential OS prognostic biomarker and guide clinical treatment for AML.