The occurrence of portal vein tumor thrombus (PVTT) is strongly correlated to the staging and poor prognosis of hepatocellular carcinoma (HCC) patients. However, the mechanisms of PVTT formation remain unclear. This study aimed to investigate differentially expressed genes (DEGs) between primary tumor (PT) and PVTT tissues and comprehensively explored the underlying mechanisms of PVTT formation. The DEGs between PT and paired PVTT tissues were analyzed using transcriptional data from the Gene Expression Omnibus (GEO) database. The expression, clinical relevance, prognostic significance, genetic alternations, DNA methylation, correlations with immune infiltration, co-expression correlations, and functional enrichment analysis of the DEGs were explored using multiple databases. As result, 12 DEGs were commonly down-expressed in PVTT compared with PT tissues among three datasets. The expression of DCN, CCL21, IGJ, CXCL14, FCN3, LAMA2, and NPY1R was progressively decreased from normal liver, PT, to PVTT tissues, whose up-expression associated with favorable survivals of HCC patients. The genetic alternations and DNA methylation of the DEGs frequently occurred, and several methylated CpG sites of the DEGs significantly correlated with outcomes of HCC patients. The immune infiltration in the tumor microenvironment of HCC was correlated with the expression level of the DEGs. Besides, the DEGs and their co-expressive genes participated in the biological processes of extracellular matrix (ECM) organization and focal adhesion. In summary, this study indicated the dysregulation of ECM and focal adhesion might contribute to the formation of PVTT. And the above seven genes might serve as potential biomarkers of PVTT occurrence and prognosis of HCC patients.

Glioblastoma (GBM), a primary malignant tumor of the central nervous system, has a very poor prognosis. Analysis of global GBM samples has revealed a variety of long non-coding RNAs (lncRNAs) associated with prognosis; nevertheless, there remains a lack of accurate prognostic markers. Using RNA-Seq, methylation, copy number variation (CNV), mutation and clinical follow-up data for GBM patients from The Cancer Genome Atlas, we performed univariate analysis, multi-cluster analysis, differential analysis of different subtypes of lncRNA and coding genes, weighted gene co-expression network analyses, gene set enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis, Gene Ontology analysis, and lncRNA CNV analyses. Our analyses yielded five lncRNAs closely related to survival and prognosis for GBM. To verify the predictive role of these five lncRNAs on the prognosis of GBM patients, the corresponding RNA-seq data from Chinese Glioma Genome Atlas were downloaded and analyzed, and comparable results were obtained. The role of one lncRNA LINC00152 has been observed previously; the others are novel findings. Expression of these lncRNAs could become effective predictors of survival and potential prognostic biomarkers for patients with GBM.

To identify novel prognostic biomarkers in renal cell carcinoma (RCC).

Aging has a significant role in the proliferation and development of cancers. This study explored the expression profiles, prognostic value, and potential roles of aging-related genes in gliomas. We designed risk score and cluster models based on aging-related genes and glioma cases using LASSO Cox regression analysis, consensus clustering analysis and univariate cox regression analyses. High risk score was related to malignant clinical features and poor prognosis based on 10 datasets, 2953 cases altogether. Genetic alterations analysis revealed that high risk scores were associated with genomic aberrations of aging-related oncogenes. GSVA analysis exhibited the potential function of the aging-related genes. More immune cell infiltration was found in high-risk group cases, and glioma patients in high-risk group may be more responsive to immunotherapy. Knock-down of CTSC, an aging-related gene, can inhibit cell cycle progression, colony formation, cell proliferation and increase cell senescence in glioma cell lines in vitro. Indeed, high expression of CTSC was associated with poor prognosis in glioma cases. In conclusion, this study revealed that aging-related genes have prognostic potential for glioma patients and further identified potential mechanisms for aging-related genes in tumorigenesis and progression in gliomas.

Inositol 1,4,5-Triphosphate Receptor Family (ITPRs) are necessary intracellular Ca2+-release channel encoders and participate in mammalian cell physiological and pathological processes. Previous studies have suggested that ITPRs participate in tumorigenesis of multiple cancers. Nevertheless, the diverse expression profiles and prognostic significance of three ITPRs in pancreatic cancer have yet to be uncovered. In this work, we examined the expression levels and survival dates of ITPRs in patients with pancreatic cancer. As a result, we identified that ITPR1 and ITPR3 expression levels are significantly elevated in cancerous specimens. Survival data revealed that over-expression of ITPR2 and ITPR3 resulted in unfavourable overall survival and pathological stage. The multivariate Cox logistic regression analysis showed that ITPR3 could be an independent risk factor for PAAD patient survival. Moreover, to investigate how ITPRs work, co-expressed genes, alterations, protein-protein interaction, immune infiltration, methylation, and functional enrichment of ITPRs were also analyzed. Then, we evaluated these findings in clinical samples. Moreover, the gain and loss of function of ITPR3 were also conducted. The electron microscope assay was employed to explore the role of ITPR3 in pancreatic cancer cell lines' endoplasmic reticulum stress. In summary, our findings demonstrated that ITPR3 has the potential to be drug targets and biomarkers for human pancreatic cancer.

Skin cutaneous melanoma (SKCM) is one of the most aggressive and life-threatening cancers with high incidence rate, metastasis rate and mortality. Early detection and stratification of risk assessment are essential to treat SKCM and to improve survival rate. The aim of this study is to construct an immune-related lncRNAs (immlncRNAs) prognosis risk model to identify immune biomarkers for early diagnosis, prognosis assessment and target immunotherapy of SKCM. For this purpose, we identified 46 immlncRNAs significantly correlated with SKCM prognosis to construct the prognostic risk model and patients were stratified into the high- and low-risk subgroups according to the developed model. The predictive efficiency of this model has been proved by K-M survival analysis and receiver operating characteristic curve. Moreover, CIBERSORT algorithms confirmed that there were differences in immune cell infiltration between the high- and low-risk groups. Functional enrichment analysis further indicated that immlncRNAs were related to a variety of immune response process signaling pathways, suggesting that relevant immlncRNAs could play an important role in the immune regulation of SKCM. Finally, subgroup analysis and multiple Cox regression analysis further proved the stability of the model. In summary, we successfully constructed a 46 immlncRNA-related prognostic risk score model with excellent predictive efficacy and provided more possibilities to investigate the immune regulation mechanisms and to develop immunotherapy of SKCM.

Circulating non-coding RNA is an ideal source to discover novel biomarkers for non-invasive screening. However, studies for the discovery of universal miRNAs in serum and exosomes for breast cancer early diagnosis are limited.

Pancreatic adenocarcinoma (PAAD) is the most serious solid tumor type throughout the world. The present study aimed to identify novel biomarkers and potential efficacious small drugs in PAAD using integrated bioinformatics analyses. A total of 4777 differentially expressed genes (DEGs) were filtered, 2536 upregulated DEGs and 2241 downregulated DEGs. Weighted gene co-expression network analysis was then used and identified 12 modules, of which, blue module with the most significant enrichment result was selected. KEGG and GO enrichment analyses showed that all DEGs of blue module were enriched in EMT and PI3K/Akt pathway. Three hub genes (ITGB1, ITGB5, and OSMR) were determined as key genes with higher expression levels, significant prognostic value and excellent diagnostic efficiency for PAAD. Additionally, some small molecule drugs that possess the potential to treat PAAD were screened out, including thapsigargin (TG). Functional in vitro experiments revealed that TG repressed cell viability via inactivating the PI3K/Akt pathway in PAAD cells. Totally, our findings identified three key genes implicated in PAAD and screened out several potential small drugs to treat PAAD.

Breast cancer is the most common lethal carcinoma worldwide and better targeted therapies are still worthy of exploration, having had some great successes already. Abnormal expression of ALKBH members were found in various cancers, and the roles played by it were the focus of attention. The ALKBH gene family encodes nine homologous enzymes (ALKBH1-8 and FTO) to repair DNA or RNA depending on Fe2+ and α-ketoglutarate (α-KG), which is related to carcinogenesis. In this study, we applied several databases to explore the roles of ALKBHs in breast cancer. We found that ALKBH members were abnormal expression in breast cancer and associated with tumor stage and subclasses. Higher alteration rates of ALKBH family were found in breast cancer. Function enrichment revealed that several cancer-associated signal pathways were related to ALKBH family such as PI3K-Akt signaling pathway and axon guidance. Infiltration of immune cells (Eosinophiles, NK CD56bright cells, mast cells, T helper cells and so on) were strongly related to ALKBHs. Moreover, we further found that there was strong correlation between ALKBH7 and higher age, later T stage, ER/PR positive and post-menopause of breast cancer patients, and patients with higher ALKBH7 expression had shorter overall survival (OS) and post progression survival (PPS). In conclusion, our findings may provide novel insights into ALKBH-targeted therapy for breast cancer patients, and ALKBH7 may be a potential prognostic biomarker.

Hepatocellular carcinoma (HCC) is an aggressive form of cancer characterized by a high recurrence rate following resection. Studies have implicated stromal and immune cells, which form part of the tumor microenvironment, as significant contributors to the poor prognoses of HCC patients. In the present study, we first downloaded gene expression datasets for HCC patients from The Cancer Genome Atlas database and categorized the patients into low and high stromal or immune score groups. By comparing those groups, we identified differentially expressed genes significantly associated with HCC prognosis. The Gene Ontology database was then used to perform functional enrichment analysis, and the STRING network database was used to construct protein-protein interaction networks. Our results show that most of the differentially expressed genes were involved in immune processes and responses and the plasma membrane. Those results were then validated using another a dataset from a HCC cohort in the Gene Expression Omnibus database and in 10 pairs of HCC tumor tissue and adjacent nontumor tissue. These findings enabled us to identify several tumor microenvironment-related genes that associate with HCC prognosis, and some those appear to have the potential to serve as HCC biomarkers.

This study was designed to identify lncRNA biomarker candidates using lung cancer data from RNA-Seq and microarray platforms separately.Lung cancer datasets were obtained from the Gene Expression Omnibus (GEO, n = 287) and The Cancer Genome Atlas (TCGA, n = 216) repositories, only common lncRNAs were used. Differentially expressed (DE) lncRNAs in tumors with respect to normal were selected from the Affymetrix and TCGA datasets. A training model consisting of the top 20 DE Affymetrix lncRNAs was used for validation in the TCGA and Agilent datasets. A second similar training model was generated using the TCGA dataset.First, a model using the top 20 DE lncRNAs from Affymetrix for training and validated using TCGA and Agilent, achieved high prediction accuracy for both training (98.5% AUC for Affymetrix) and validation (99.2% AUC for TCGA and 92.8% AUC for Agilent). A similar model using the top 20 DE lncRNAs from TCGA for training and validated using Affymetrix and Agilent, also achieved high prediction accuracy for both training (97.7% AUC for TCGA) and validation (96.5% AUC for Affymetrix and 80.9% AUC for Agilent). Eight lncRNAs were found to be overlapped from these two lists.

Hepatocellular carcinoma (HCC) is the most common high malignancy with insidious onset, invasive fast-growing, high recurrence rate and fatality. YTH domain family plays essential roles in development of HCC. However, the biological function of YTH domain family in HCC have not been clarified. Here, through evaluating the expression profiles of YTH domain family, we found that upregulated YTHDF1 might be more significant and valuable in development and progression of HCC. There was a strong correlation between YTHDC1, YTHDF1 and YTHDF2 and pathological stage of HCC patients. Kaplan-Meier plotter revealed that HCC patients with high level of YTHDF1 and YTHDF2 were highly related to a shorter overall survival time, and low level of YTHDF1 (p = 0.0017) has an important association with a longer progression-free survival time. Genetic alterations using cBioPortal revealed that the alteration rates of YTHDF3 were the highest. We also found that the functions of YTH domain family were linked to several cancer-associated pathways, including peptidyl-serine modification, peptidyl-tyrosine modification and negative regulation of cellular component movement. TIMER database indicated that the YTH domain family had a strong relationship with the infiltration of six types of immune cells (macrophages, neutrophils, CD8+ T-cells, B-cells, CD4+ T-cells and dendritic cells). Next, Ualcan databases revealed that the global methylation levels of YTHDC1 was higher in HCC patients, while YTHDF2 was lower in HCC patients. In conclusion, our findings will enhance the understanding of YTH domain family in HCC pathology, and provide novel insights into YTH-targeted therapy for HCC patients.

Bromodomain (BRD)-containing proteins are a class of epigenetic readers with unique recognition for N-acetyl-lysine in histones and functions of gene transcription and chromatin modification, known to be critical in various cancers. However, little is known about the roles of distinct BRD-containing protein genes in hepatocellular carcinoma (HCC). Most recently, we investigated the transcriptional and survival data of BRD1, BRD2, BRD3, BRD4, BRD7, BRD8, BRD9 in HCC patients through ONCOMINE, UALCAN, Human Protein Atlas, GEPIA, cBioPortal, STRING, TIMER databases. BRD1/2/3/4/7/8/9 were over-expressed in HCC and were significantly associated with clinical cancer stages and pathological tumor grades. High mRNA expressions of BRD4/8/9 were promising candidate biomarkers in HCC patients. The rate of sequence alternations in BRD1/2/3/4/7/8/9 was relatively high (52%) in HCC patients, and the genetic alternations were correlated with shorter overall survival and disease-free survival in HCC patients. Additionally, the mRNA expression levels of individual BRD genes were significantly positively associated with the immune infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. And the associations between BRD1/2/3/4/7/8/9 and diverse immune marker sets showed a significance. Overall, these results indicated that BRD4/8/9 could be potential prognostic markers and druggable epigenetic targets in HCC patients.

The role of gut microbes (GM) and their metabolites in colorectal cancer (CRC) development has attracted increasing attention. Several studies have identified specific microorganisms that are closely associated with CRC occurrence and progression, as well as key genes associated with gut microorganisms. However, the extent to which gut microbes-related genes can serve as biomarkers for CRC progression or prognosis is still poorly understood. This study used a bioinformatics-based approach to synthetically analyze the large amount of available data stored in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Through this analysis, this study identified two distinct CRC molecular subtypes associated with GM, as well as CRC markers related to GM. In addition, these new subtypes exhibit significantly different survival outcomes and are characterized by distinct immune landscapes and biological functions. Gut microbes-related biomarkers (GMRBs), IL7 and BCL10, were identified and found to have independent prognostic value and predictability for immunotherapeutic response in CRC patients. In addition, a systematic collection and review of prior research literature on GM and CRC provided additional evidence to support these findings. In conclusion, this paper provides new insights into the underlying pathological mechanisms by which GM promotes the development of CRC and suggests potentially viable solutions for individualized prevention, screening, and treatment of CRC.

Despite the better prognosis given by surgical resection and chemotherapy in low-grade glioma (LGG), progressive transformation is still a huge concern. In this case, the S100A gene family, being capable of regulating inflammatory responses, can promote tumor development.

GSDM family is a group of critical proteins that mediate pyroptosis and plays an important role in cell death and inflammation. However, their specific function in clear cell renal cell carcinoma (ccRCC, KIRC) have not been clarified comprehensively. In this study, we assessed the roles of the GSDM family in expression, prognostic value, functional enrichment analysis, genetic alterations, immune infiltration and DNA methylation in ccRCC patients by using different bioinformatics databases. We found that the expression levels of GADMA-E were significantly higher in ccRCC tissues compared with normal tissues, while the expression level of PJVK was decreased. Moreover, survival analysis indicated that upregulation of GSDME was related to poor overall survival (OS) and recurrence-free survival (RFS) of ccRCC patients. The main function of differentially expressed GSDM homologs was related to ion transport. We also found that the expression profiles of the GSDM family were highly correlated with infiltrating immune cells (i.e., CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils and dendritic cells), and there were significant differences in the expression of GSDM family in different ccRCC immune subtypes. Furthermore, DNA methylation analysis indicated that the DNA methylation levels of GSDMA/B/D/E were decreased, while the DNA methylation level of PJVK was increased. In conclusion, this study provides integrated information about abnormal GSDM family members as potential biomarkers for the diagnosis and prognosis of ccRCC. Especially, GSDME was a potential clinical target and prognostic biomarkers for patients with ccRCC.

The current study aimed to understand the genetic landscape and investigate the diagnostic and prognostic biomarkers of primary hepatocellular carcinoma (HCC).

Exosomes play a crucial role in tumor initiation and progression, yet the precise involvement of exosome-related genes (ERGs) in lung adenocarcinoma (LUAD) remains unclear.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins that are reported to play a crucial role in the pathogenic process of multiple malignancies. However, their expression patterns, clinical application significance and prognostic values in invasive breast carcinoma (BRCA) remain unknown. In this study, we investigated hnRNP family members in BRCA using accumulated data from Oncomine 4.5, UALCAN Web portal and other available databases. We explored the expression and prognostic value level of hnRNPs in BRCA. We further analyzed their association with the clinicopathological features of BRCA patients. Subsequently, we calculated the alteration frequency of hnRNPs, constructed the interaction network of hnRNPs, and examined the potential coexpression genes of hnRNPs, revealing that HNRNPU and SYNCRIP are the core molecular genes requiring further investigation for BRCA. We validated the immunohistochemistry (IHC) pattern to simulate clinical applications based on pathology. Cell function experiments conducted in vitro indicated that HNRNPU can promote epithelial-mesenchymal transition, functionally stimulating the invasion capacity and inhibiting the viability of invasive BRCA cells. In summary, our systematic analysis demonstrated that HNRNPU was the key molecule that played a fundamental role in BRCA metastasis, which may facilitate the development of new diagnostic and prognostic markers for the analysis of BRCA progression.

The minichromosome maintenance (MCM) gene family comprises of ten members with key roles in eukaryotic DNA replication and are associated with the occurrence and progression of many tumors. However, whether the MCM family contributes to lung squamous cell carcinoma (LUSC) is unclear. In this study, we performed bioinformatic analysis to identify the roles of MCM genes in patients with LUSC. We also evaluated their differential gene expression, prognostic correlation, DNA methylation, functional enrichment of genetic alterations, and immunomodulation. According to the Tumor Immune Estimation Resource database, the expression of MCM2-10 mRNA was elevated in LUSC tissues. According to the Gene Expression Profiling Interactive Analysis database, MCM2-8 and MCM10 were considerably upregulated in LUSC tissues, and protein levels of all MCMs were increased in LUSC tissues. In addition, among the MCM family members, the expression of MCM3 and MCM7 showed the strongest correlation with the prognoses of patients with LUSC. To clarify the role and mechanisms of the MCM family, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment studies were performed. We detected a significant correlation between the expression patterns of MCM family members and infiltrating immune cells. In conclusion, our results improve the understanding of the aberrant expression of MCM family members in LUSC. These findings demonstrate the potential of the MCM family as therapeutic targets and biomarkers for the diagnosis and prognosis of LUSC.