Expression In Human Cancer Research Articles

The Significance of Secreted Phosphoprotein 1 in Multiple Human Cancers.

Malignant tumor represents a major reason for death in the world and its incidence is growing rapidly. Developing the tools for early diagnosis is possibly a promising way to offer diverse therapeutic options and promote the survival chance. Secreted phosphoprotein 1 (SPP1), also called Osteopontin (OPN), has been demonstrated overexpressed in many cancers. However, the specific role of SPP1 in prognosis, gene mutations, and changes in gene and miRNA expression in human cancers is unclear. In this report, we found SPP1 expression was higher in most of the human cancers. Based on Kaplan-Meier plotter and the PrognoScan database, we found high SPP1 expression was significantly correlated with poor survival in various cancers. Using a large dataset of colon adenocarcinoma (COAD), head and neck cancer (HNSC), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC) patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, this study identified 22 common genes and 2 common miRNAs. GO, and KEGG paths analyses suggested that SPP1 correlated genes were mainly involved in positive regulation of immune cell activation and infiltration. SPP1-associated genes and miRNAs regulatory networks suggested that their interactions may play a role in the progression of four selected cancers. SPP1 showed significant positive correlation with the immunocyte and immune marker sets infiltrating degrees. All of these data provide strong evidence that SPP1 may promote tumor progress through interacting with carcinogenic genes and facilitating immune cells’ infiltration in COAD, HNSC, LUAD, and LUSC.

Clinicopathological and Prognostic Significance of CBX3 Expression in Human Cancer: a Systematic Review and Meta-analysis.

Background Chromebox protein homolog 3 (CBX3) as a member of the heterochromatin-associated protein 1 (HP1) family has been reported to be overexpressed in human cancer tissues. Numerous studies have shown the relationship between the CBX3 expression and clinicopathological factor or prognosis in malignant tumors, but their results are inconsistent. To address these results, a meta-analysis was described to investigate the prognostic value and clinicopathological significance of CBX3 expression in human malignant neoplasms. Methods PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure (CNKI) were used to search eligible literatures, including publications prior to September 2019. The role of CBX3 in cancer prognosis and clinicopathological characteristics was assessed by pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Results Eleven studies with 1682 cancer patients were enrolled in this meta-analysis. This analysis demonstrated that the patients' increased CBX3 expression was significantly associated with poor overall survival (OS) (univariate analysis: HR = 1.81, 95% CI 1.46-2.25; multivariate analysis: HR = 1.95, 95% CI 1.63-2.34). Subgroups analysis by tumor type also indicated that high expression of CBX3 was correlated with poor OS in tongue squamous cell carcinoma (HR = 3.31, 95% CI 2.03-5.39), lung cancer (HR = 1.66, 95% CI 1.21-2.29), genitourinary cancer (HR = 2.03, 95% CI 1.15-3.58), and digestive cancer (HR = 1.48, 95% CI 1.23-1.79). For clinicopathological features, high expression of CBX3 was associated with lymph node metastasis (OR = 2.96, 95% CI 1.42-6.20) and lager tumor size (OR = 1.60, 95% CI 1.12-2.28). Conclusion The results of this meta-analysis indicated that CBX3 expression may be a novel biomarker for predicting patient prognosis and clinicopathological parameters in multiple human cancer.

Regulation of microRNA-497 expression in human cancer.

MicroRNAs (miRNAs/miRs) are a type of non-coding single-stranded RNA, with a length of ~22 nt, which are encoded by endogenous genes and are involved in the post-transcriptional regulation of gene expression in animals and plants. Studies have demonstrated that miRNAs play an important role in the occurrence, development, metastasis, diagnosis and treatment of cancer. In recent years, miR-497 has been identified as one of the key miRNAs in a variety of cancer types and has been shown to be downregulated in a variety of solid tumors. However, the regulation of miR-497 expression involves a complex network, which is affected by several factors. The aim of the present review was to summarize the mechanism of regulation of miR-497 expression at the pre-transcriptional and transcriptional levels in cancer, as well as the role of miR-497 expression imbalance in cancer diagnosis, treatment and prognosis. The regulatory mechanisms of miR-497 expression may aid in our understanding of the causes of miR-497 expression imbalance and provide a reference value for further research on the diagnosis and treatment of cancer.

PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin.

PurposeThe significance of periodic tryptophan protein 1 (PWP1) expression in human cancer and its molecular mechanism of action have not been reported so far.Materials and MethodsImmunohistochemistry was performed to analyze the expression of PWP1 in non-small cell lung cancer (NSCLC) tissues and statistical analysis was applied to analyze the relationship between PWP1 expression and the clinicopathological factors. The effects of PWP1 on NSCLC proliferation and invasion were determined by colony formation, transwell and MTT assays. Western blot analysis (WB), dual-luciferase reporter gene assays and immunofluorescence staining were performed to demonstrate whether PWP1 stimulates Wnt pathway and inhibits Hippo pathway. Co-immunoprecipitation (Co-ip) assays were used to confirm the potential role of PWP1 in Wnt and Hippo signaling pathways.ResultsPWP1 expression in NSCLC was higher than that in normal bronchial epithelium and normal submucosal glands. In addition, PWP1 expression had a positive correlation with poor differentiation, high pathological tumor-node-metastasis (TNM) stage, and lymph node metastasis. Kaplan–Meier database demonstrated that the overall survival time of patients with high PWP1 expression was significantly shorter than that of patients with low PWP1 expression. Mechanistically, we found that PWP1 could interact with DVL2 to upregulate β-catenin (thereby activating the Wnt pathway), whereas PWP1 could interact with Merlin (NF2) to downregulate p-MST1 (thereby inhibiting the Hippo signaling pathway). The effects of PWP1 on promoting the Wnt pathway or inhibiting the Hippo pathway were offset in DVL2- or Merlin-knockdown cells transiently overexpressing PWP1.ConclusionPWP1 expression in NSCLC was correlated with poor prognosis. PWP1 enhanced the activity of the Wnt pathway by interacting with DVL2, whereas PWP1 inhibited the activity of the Hippo pathway by interacting with Merlin. Together, these two effects promoted the detrimental biological behaviors of NSCLC cells.

High expression of LEF1 correlates with poor prognosis in solid tumors, but not blood tumors: a meta-analysis.

Background: Previously published studies have indicated that lymphoid enhancer-binding factor 1 (LEF1) expression could be recognized as a valuable biomarker to evaluate clinical outcome for various types of malignant cancer, but the results remained controversial. Therefore, we conducted this meta-analysis to pool the published estimates and discuss the relationship of LEF1 expression with cancer prognosis. Methods: Five electronic databases Pubmed, Web of Science, Embase, CNKI, and Wanfang were systematically searched for eligible literatures. Hazard ratios (HRs) and 95% confidence intervals (CIs) from the included studies were combined to estimate the effect of LEF1 expression on cancer patients’ survival. Results: Eleven original studies met the criteria and were enrolled for analysis. The results indicated that compared with patients in low LEF1 expression group, patients in high LEF1 expression group tended to have shorter overall survival (HR = 1.74, 95% CI: 1.06–2.86, P=0.029), especially for patients with solid tumors (HR = 2.39, 95% CI: 1.86–3.08, P=0.000). Conclusions: Individual evidence about the prognostic value of LEF1 expression in human cancers was limited. Our meta-analysis supported the suggestion that elevated LEF1 expression could function as a promising biomarker to predict the clinical outcomes for malignant cancers, especially solid tumors. More high-quality clinical studies are warranted to highlight the prognostic value of LEF1 expression in human cancers.

Increased expression of secreted frizzled related protein 1 (SFRP1) predicts ampullary adenocarcinoma recurrence

Ampullary adenocarcinoma is a rare gastrointestinal cancer in which WNT signalling dysregulation has been previously reported. Secreted frizzled related protein 1 (SFRP1) is one of the extracellular ligands of WNT signalling. We performed bioinformatics analyses of SFRP1 expression in human cancer. Microarray analysis of SFRP1 in periampullary adenocarcinoma was obtained from the Gene Expression Omnibus GSE39409 dataset. SFRP1 expression in ampullary adenocarcinoma was detected by immunohistochemistry staining and correlated with patients’ clinical outcomes. Our results showed that SFRP1 expression had different clinical applications in all types of human cancer. No detected alteration of SFPR1 gene and SFRP1 expression in ampullary adenocarcinoma was lower than that in other periampullary adenocarcinomas. However, high expression levels of SFRP1 protein were correlated with cancer recurrence, peritoneal carcinomatosis and poor patient prognosis. Gene set enrichment analysis showed downregulation of multiple WNT-related genes in primary culture cells from ampullary adenocarcinoma, but SFRP1 expression was increased. We found an interaction between WNT, bone morphogenetic protein and hedgehog signalling with SFRP1. Furthermore, a high expression of SFRP1 predicted poor prognosis for ampullary adenocarcinoma patients. Because it is a multifunctional protein, SFRP1 targeting serves as a potential therapy for ampullary adenocarcinoma patients.

Prognostic value of CD44v9 expression in human cancers: A systematic review and meta-analysis.

Background:The prognostic significance of CD44 variant-9 (CD44v9) expression in human cancers has been investigated in several studies, however, definite conclusion has not be reached. The aim of this systematic review and meta-analysis was to evaluate the prognostic significance of CD44v9 expression in various cancers.Methods:Three common databases were searched and retrieved studies were assessed using the inclusion and exclusion criteria. The further analyses for overall survival (OS), recurrence-free survival (RFS), and clinicopathological parameters were performed.Results:Fifteen studies containing 1633 cancer patients were included into this research. Patients with positive CD44v9 expression tended to have shorter OS (hazard ratio [HR] = 1.93, 95% confidence interval [CI] = 1.48–2.52, P < .01) and RFS (HR = 3.60, 95% CI = 1.52–8.53, P < .01) when compared with patients with negative CD44v9 expression. Positive CD44v9 expression was associated with larger tumor size (P = .04), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), and more advanced clinical stage (P < .01) when compared with negative CD44v9 expression.Conclusion:Positive CD44v9 expression predicted worse prognosis in human cancers compared with negative CD44v9 expression. CD44v9 expression could serve as a prognostic factor of human cancers.

Clinicopathological significance and prognosis of long noncoding RNA SNHG16 expression in human cancers: a meta-analysis

BackgroundRecent studies have highlighted the important role of long non-coding RNA SNHG16 in various human cancers. Here, we conducted a meta-analysis to investigate the effect of SNHG16 expression on clinicopathological features and prognosis in patients with different kinds of human cancers.MethodsWe performed a systematic search in electronic databases including PubMed, EMBASE, Cochrane Library and Web of Science, to investigate the potential association between SNHG16 expression and prognostic significance and clinical features in cancer patients. Odds ratios (ORs) or hazards ratios (HRs) with corresponding 95% confidence intervals (95% CIs) were pooled to estimate the prognosis value of SNHG16 by StataSE 15.0 software.ResultsA total of 16 eligible studies with 1299 patients were enrolled in our meta-analysis. The results revealed that increased expression level of SNHG16 was significantly associated with larger tumor size (OR: 3.357; 95% CI: 2.173–5.185; P < 0.001), advanced TNM stage (OR: 2.930; 95% CI: 1.522–5.640; P = 0.001) and poor histological grade (OR: 3.943; 95% CI: 1.955–7.952; P < 0.001), but not correlated with smoking status (P = 0.489), sex (P = 0.932), distant metastasis (P = 0.052), or lymph node metastasis (P = 0.155). Moreover, the pooled HR showed that elevated expression SNHG16 was associated with a significantly poorer overall survival (OS) (HR = 1.866, 95% CI: 1.571–2.216, P < 0.001). For the set of cancer types, high expression of SNHG16 was significantly associated with shorter OS in patients with cancers of the urinary system (HR: 2.523, 95% CI:1.540–4.133; P <0.001), digestive system (HR: 2.406, 95% CI:1.556–3.721; P <0.001), and other cancers (including glioma and non-small cell lung cancer) (HR: 1.786, 95% CI:1.406–2.267; P <0.001).ConclusionsLncRNA SNHG16 overexpression might serve as an unfavorable prognostic factor, which provides a basis for medical workers to evaluate the prognosis of patients and to help the decision-making process.

MicroRNAs: New-Age Panacea in Cancer Therapeutics.

MicroRNAs (miRNAs) are small (~ 18-25 nucleotides in length), endogenous, non-coding RNAs, which regulate gene expression. Numerous studies have demonstrated the dysregulation of miRNA expression in human cancers through various mechanisms, which include genetic alteration of miRNA genes, abnormal transcriptional control of miRNAs, anomalous epigenetic changes, and defective miRNA biogenesis machinery. They may function as either oncomiRs or tumor suppressor miRNAs in a tissue or cell-specific manner. The dysregulated miRNAs are known to affect the hallmarks of cancer, and some of these miRNAs have shown therapeutic promise in pre-clinical and clinical studies. Here, we briefly touch upon various aspects of miRNA biology with a particular focus on their roles in cancer.

IL-6 influences PD-L1 expression in monocytes and macrophages by effecting protein tyrosine phosphatase receptor type O expression in-human breast cancer.

e15570 Background: We have previously discovered a relationship between the low expression of protein tyrosine phosphatase, receptor type O (PTPRO) in tumor-infiltrating T cells and immunosuppression. The aim of the present study was to investigate the relationship between decreased PTPRO and increased programmed death ligand 1 (PD-L1) in both the peripheral monocytes and tumor-infiltrating macrophages of human breast cancer (BC). Methods: The expression and correlation of all the indices were explored in monocytes and tumor infiltrating macrophages within both human and mice BC. The mechanic regulations were studied by using both in vitro and in vivo studies. Results: We found a significant decrease in PTPRO in BC peripheral monocytes that was associated with increased PD-L1 expression in peripheral monocytes and tumor-associated macrophages (TAMs) in BC. Monocyte PD-L1 and PTPRO therefore could serve as valuable prognostic indicators for post-surgery patients with BC and were associated with increased T cell exhaustion (Tim3+ T cells). A depletion of PTPRO promoted PD-L1 secretion in both monocytes and macrophages through the JAK2/STAT1 and JAK2/STAT3/c-MYC pathways. Increased IL-6 expression was associated with activation of JAK2/STAT3/c-MYC and with decreased PTPRO expression through the STAT3/c-MYC/miR-25-3p axis. Monocytes and TAMs showed significantly increased miR-25-3p expression, which could target the 3' untranslated region of PTPRO. The miR-25-3p expression positively correlated with serum IL-6 levels, but inversely correlated with PTPRO in BC monocytes. IL-6/STAT3/c-MYC activation enhanced in vitro miR-25-3p transcription and decreased PTPRO, while further promoting PD-L1 secretion. Adoptive cell transfer of c-MYC/miR-25-3p–modified monocytes promoted tumor growth by downregulating PTPRO and causing a PD-L1–induced immunosuppression in breast tumor model. Conclusions: Increased serum IL-6 downregulated PTPRO expression in BC monocytes and macrophages by activating STAT3/c-MYC/miR-25-3p and by further enhancing PD-L1 expression through JAK2/STAT1 and JAK2/STAT3/c-MYC signaling.

Clinicopathological and prognostic value of SNHG6 in cancers: a systematic review and a meta-analysis

BackgroundDysregulation of the long non-coding RNA small nucleolar RNA host gene 16 (lncRNA SNHG6) has been found in multiple cancers. However, a definite conclusion on the clinical value of lncRNA SNHG6 expression in human cancers has not been determined. The purpose of the present meta-analysis was to comprehensively elucidate the association between SNHG6 expression and clinical outcomes in cancers.MethodsA systematic search was performed through the PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wangfang databases for relevant studies. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were collected to estimate the prognostic value, and the odds ratios (ORs) with 95% CIs were used to evaluate the relationship between lncRNA SNHG6 expression and clinicopathological features, including tumor invasion depth, lymph node metastasis (LNM), distance metastasis (DM), and TNM stage.ResultsIn total, 914 patients from 13 studies were included in this meta-analysis. The pooled results suggested that evaluated SNHG6 expression could predict an unfavorable overall survival (OS) (HR = 2.04, 95% CI:1.56–2.52) with no heterogeneity (I2 = 0.0%, p = 0.996). Subgroup analysis indicated a significant association between high SNHG6 expression and shorter OS in those studies with digestive system cancers (HR = 2.05, 95% CI: 1.47–2.62), or with sample size < 70 (HR = 2.70, 95% CI: 1.29–4.11), or with multivariate analysis (HR = 2.04, 95% CI: 1.44–2.64). Moreover, elevated SNHG6 expression was positively associated with tumor invasion depth (OR = 1.76, 95% CI: 1.18–2.63), LNM (OR = 1.60, 95% CI: 1.18–2.17), DM (OR = 1.90, 95% CI: 1.37–2.64) and advanced TNM stage (OR = 1.88, 95% CI: 1.36–2.60) in patients with cancers.ConclusionsHigh lncRNA SNHG6 expression was correlated with tumor invasion depth, LNM, DM, and advanced TNM stage, suggesting that SNHG6 may serve as a promising prognostic biomarker of human cancers.

Oncogenesis and Tumor Inhibition by MicroRNAs and its Potential Therapeutic Applications: A Systematic Review.

MicroRNAs appear as small molecule modifiers, which improve many new findings and mechanical illustrations for critically important biological phenomena and pathologic events. The best-characterized non-coding RNA family consists of about 2600 human microRNAs. Rich evidence has revealed their crucial importance in maintaining normal development, differentiation, growth control, aging, modulation of cell survival or apoptosis, as well as migration and metastasis as microRNAs dysregulation leads to cancer incidence and progression. By far, microRNAs have recently emerged as attractive targets for therapeutic intervention. The rationale for developing microRNA therapeutics is based on the premise that aberrantly expressed microRNAs play a significant role in the emergence of a variety of human diseases ranging from cardiovascular defects to cancer, and that repairing these microRNA deficiencies by either antagonizing or restoring microRNA function may yield a therapeutic benefit. Although microRNA antagonists are conceptually similar to other inhibitory therapies, improving the performance of microRNAs by microRNA replacement or inhibition that is a less well- described attitude. In this assay, we have condensed the last global knowledge and concepts regarding the involvement of microRNAs in cancer emergence, which has been achieved from the previous studies, consisting of the regulation of key cancer-related pathways, such as cell cycle control and the DNA damage response and the disruption of profile expression in human cancer. Here, we have reviewed the special characteristics of microRNA replacement and inhibition therapies and discussed explorations linked with the delivery of microRNA mimics in turmeric cells. Besides, the achievement of biomarkers based on microRNAs in clinics is considered as novel non-invasive biomarkers in diagnostic and prognostic assessments.

Preferential Expression of B7-H6 in Glioma Stem-Like Cells Enhances Tumor Cell Proliferation via the c-Myc/RNMT Axis.

B7 homologue 6 (B7-H6), a newly identified member of the B7 costimulatory molecule family, is not only a crucial regulator of NK cell-mediated immune responses through binding to NKp30 but also has clinical implications due to its abnormal expression in human cancers. Here, we show that B7-H6 expression is abnormally upregulated in glioma tissue and that B7-H6 is coexpressed with stem cell marker Sox2. Intriguingly, B7-H6 was rarely detected on the surface of glioma cell lines but was abundantly expressed in glioma stem-like cells (GSLCs) that were derived from the glioma cell lines in vitro. Surprisingly, B7-H6 was the only one that was preferentially expressed in the GSLCs among the B7 family members. Functionally, knockdown of B7-H6 in GSLCs by siRNAs led to the inhibition of cell proliferation, with decrease in the expression of the oncogene Myc as well as inactivation of PI3K/Akt and ERK/MAPK signaling pathways. Moreover, we determined that three genes CBL (Casitas B-Lineage Lymphoma Proto-Oncogene), CCNT1 (Cyclin T1), and RNMT (RNA guanine-7 methyltransferase) were coexpressed with B7-H6 and c-myc in glioma tissue samples from the TCGA database and found, however that only RNMT expression was inhibited by the knockdown of B7-H6 expression in the GSLCs, suggesting the involvement of RNMT in the B7-H6/c-myc axis. Extending this to 293T cells, we observed that knocking out of B7-H6 with CRISPR-Cas9 system also suppressed cell proliferation. Thus, our findings suggest B7-H6 as a potential molecule for glioma stem cell targeted immunotherapy.

Analyzing the prognostic value of DKK1 expression in human cancers based on bioinformatics.

BackgroundThe Dickkopf1 (DKK1) gene encodes a protein that belongs to the Dickkopf family. The protein can inhibit the Wnt signaling pathway which plays a key role in the carcinogenesis and progression of various types of cancers. Based on this, we hypothesized that the differential expression of DKK1 may figure significantly in cancers by regulating Wnt signaling pathway transduction. In this study, we conducted bioinformatics analysis to evaluate the prognostic and therapeutic value of DKK1 expression level in human cancers.MethodsThe expression level was analyzed by using the Oncomine database and Gene Expression Profiling Interactive Analysis tool. The analysis of prognosis was conducted by using the UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA), and DriverDBv3 databases. We also investigated using DKK1 promoter methylation to define cancer types through the UALCAN database. Meanwhile, the related functional networks of DKK1 were analyzed by using the GeneMANIA interactive tool and Cytoscape software. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted using the Metascape online website, and we used the cBioPotartal database to explored DKK1 expression, aberrant information, and the co-expression genes in the subgroups of lung cancer. Finally, we performed the overall survival (OS) meta-analysis of the DKK1 expression in lung squamous cell carcinoma (LUSC) via the Lung Cancer Explorer (LCE).ResultsDKK1 was differentially expressed in different types of human cancers. DKK1 was overexpressed in human cancers including head and neck squamous cell carcinoma (HNSC), LUSC, and pancreatic adenocarcinoma (PAAD). Overexpression of DKK1 indicated adverse OS in bladder urothelial carcinoma (BLCA), HNSC, and PADD, but no difference in OS was found between the LUSC and healthy groups. The high expression of DKK1 was also associated with shorter disease-free survival (DFS) in HNSC, LUSC, and PAAD. Gene regulation network analysis indicated that DKK1 was mainly involved in Wnt signaling pathways and several other signaling pathways.ConclusionsOur findings showed that DKK1 is significantly expressed in various cancers and could be a biomarker for targeted therapy and a predictor for prognosis of these specific cancers. The bioinformatics analysis revealed a significant overexpression of DKK1 in HNSC, LUSC, and PAAD, with DKK1 overexpression being associated with adverse outcome in these patients, but how DKK1 expression levels relate to hematological malignancies and prognosis is still unclear. These new insights into the function of DKK1 may provide a basis for new targeted drug therapy and an avenue for further investigation into the mechanisms underlying carcinogenesis of DKK1 in different cancer types.

Biosystem Analysis of the Hypoxia Inducible Domain Family Member 2A: Implications in Cancer Biology.

The expression of HIGD2A is dependent on oxygen levels, glucose concentration, and cell cycle progression. This gene encodes for protein HIG2A, found in mitochondria and the nucleus, promoting cell survival in hypoxic conditions. The genomic location of HIGD2A is in chromosome 5q35.2, where several chromosomal abnormalities are related to numerous cancers. The analysis of high definition expression profiles of HIGD2A suggests a role for HIG2A in cancer biology. Accordingly, the research objective was to perform a molecular biosystem analysis of HIGD2A aiming to discover HIG2A implications in cancer biology. For this purpose, public databases such as SWISS-MODEL protein structure homology-modelling server, Catalogue of Somatic Mutations in Cancer (COSMIC), Gene Expression Omnibus (GEO), MethHC: a database of DNA methylation and gene expression in human cancer, and microRNA-target interactions database (miRTarBase) were accessed. We also evaluated, by using Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), the expression of Higd2a gene in healthy bone marrow-liver-spleen tissues of mice after quercetin (50 mg/kg) treatment. Thus, among the structural features of HIG2A protein that may participate in HIG2A translocation to the nucleus are an importin α-dependent nuclear localization signal (NLS), a motif of DNA binding residues and a probable SUMOylating residue. HIGD2A gene is not implicated in cancer via mutation. In addition, DNA methylation and mRNA expression of HIGD2A gene present significant alterations in several cancers; HIGD2A gene showed significant higher expression in Diffuse Large B-cell Lymphoma (DLBCL). Hypoxic tissues characterize the “bone marrow-liver-spleen” DLBCL type. The relative quantification, by using qRT-PCR, showed that Higd2a expression is higher in bone marrow than in the liver or spleen. In addition, it was observed that quercetin modulated the expression of Higd2a gene in mice. As an assembly factor of mitochondrial respirasomes, HIG2A might be unexpectedly involved in the change of cellular energetics happening in cancer. As a result, it is worth continuing to explore the role of HIGD2A in cancer biology.

TP63 isoform expression is linked with distinct clinical outcomes in cancer.

BackgroundHalf of muscle-invasive bladder cancer patients will relapse with metastatic disease and molecular tests to predict relapse are needed. TP63 has been proposed as a prognostic biomarker in bladder cancer, but reports associating it with clinical outcomes are conflicting. Since TP63 is expressed as multiple isoforms, we hypothesized that these conflicting associations with clinical outcome may be explained by distinct opposing effects of differential TP63 isoform expression.MethodsUsing RNA-Seq data from The Cancer Genome Atlas (TCGA), TP63 isoform-level expression was quantified and associated with clinical covariates (e.g. survival, stage) across 8,519 patients from 29 diseases. A comprehensive catalog of TP63 isoforms was assembled using gene annotation databases and de novo discovery in bladder cancer patients. Quantifications and un-annotated TP63 isoforms were validated using quantitative RT-PCR and a separate bladder cancer cohort.FindingsDNp63 isoform expression was associated with improved bladder cancer patient survival in patients with a luminal subtype (HR = 0.89, CI 0.80–0.99, Cox p = 0.034). Conversely, TAp63 isoform expression was associated with reduced bladder cancer patient survival in patients with a basal subtype (HR = 2.35, CI 1.64–3.37, Cox p < 0.0001). These associations were observed in multiple TCGA disease cohorts and correlated with epidermal differentiation (DNp63) and immune-related (TAp63) gene signatures.InterpretationThese results comprehensively define TP63 isoform expression in human cancer and suggest that TP63 isoforms are involved in distinct transcriptional programs with opposing effects on clinical outcome.

Humoral immune responses against cancer-testis antigens in human malignancies.

Cancer-testis antigens (CTAs) are a class of cancer antigens with extensive expression in human cancers. Many researchers have detected antibody responses against these tumor antigens in serum of cancer patients. To evaluate the relevance of humoral immune responses against CTAs in clinical outcome of cancer patientsMETHODS: We searched PubMed/Medline with the key words cancer-testis antigen, antibody, humoral response and cancer. Humoral immune responses against CTAs have been detected in several human malignancies including skin, breast, brain and ovarian cancers. Some studies have shown associations between the presence of these responses in patients and patients' survival. Humoral immune responses against CTAs are putative biomarkers for cancer detection and follow-up.

Long non-coding RNA linc00152 acting as a promising oncogene in cancer progression.

The incidence and mortality rate of cancer continues to gradually increase, although considerable research effort has been directed at elucidating the molecular mechanisms underlying biomarkers responsible for tumorigenesis. Accumulated evidence indicates that the long non-coding RNAs (lncRNAs), which are transcribed but not translated into functional proteins, contribute to cancer development. Recently, linc00152 (an lncRNA) was identified as a potent oncogene in various cancer types, and shown to be involved in cancer cell proliferation, invasiveness, and motility by sponging tumor-suppressive microRNAs acting as a competing endogenous RNA, binding to gene promoters acting as a transcriptional regulator, and binding to functional proteins. In this review, we focus on the oncogenic role of linc00152 in tumorigenesis and provided an overview of recent clinical studies on the effects of linc00152 expression in human cancers.

Prognostic significance of KIF2A and KIF20A expression in human cancer: A systematic review and meta-analysis.

Background:The kinesin family (KIF) is reported to be aberrantly expressed and significantly correlated with survival outcomes in patients with various cancers. This meta-analysis was carried out to quantitatively evaluate the prognostic values of partial KIF members in cancer patients.Methods:Two well-known KIF members, KIF2A and KIF20A, were investigated to evaluate their potential values as novel prognostic biomarkers in human cancer. A comprehensive literature search was carried out of the PubMed, EMBASE, Cochrane Library, and Web of Science databases up to April 2019. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association of KIF2A and KIF20A expression with overall survival (OS) and clinicopathological parameters.Results:Twenty-five studies involving 7262 patients were finally incorporated, including nine about KIF2A and sixteen about KIF20A. Our results indicated that patients with high expression of KIF2 and KIF20A tended to have shorter OS than those with low expression (HR = 2.23, 95% CI = 1.87–2.65, P < .001; HR = 1.77, 95% CI = 1.57–1.99, P < .001, respectively). Moreover, high expression of these 2 KIF members was significantly associated with advanced clinical stage (OR = 1.98, 95% CI: 1.57–2.50, P < .001; OR = 2.63, 95% CI: 2.03–3.41, P < .001, respectively), positive lymph node metastasis (OR = 2.32, 95% CI: 1.65–3.27, P < .001; OR = 2.13, 95% CI: 1.59–2.83, P < .001, respectively), and distant metastasis (OR = 2.20, 95% CI: 1.21–3.99, P = .010; OR = 5.25, 95% CI: 2.82–9.77, P < .001, respectively); only high KIF20A expression was related to poor differentiation grade (OR = 1.82, 95% CI: 1.09–3.07, P = .023).Conclusions:High expression of KIF2 and KIF20A in human cancer was significantly correlated with worse prognosis and unfavorable clinicopathological features, suggesting that these 2 KIF members can be used as prognostic biomarkers for different types of tumors. PROSPERO REGISTRATION NUMBER: CRD42019134928.

Differentially Methylated Super-Enhancers Regulate Target Gene Expression in Human Cancer

Current literature suggests that epigenetically regulated super-enhancers (SEs) are drivers of aberrant gene expression in cancers. Many tumor types are still missing chromatin data to define cancer-specific SEs and their role in carcinogenesis. In this work, we develop a simple pipeline, which can utilize chromatin data from etiologically similar tumors to discover tissue-specific SEs and their target genes using gene expression and DNA methylation data. As an example, we applied our pipeline to human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV + OPSCC). This tumor type is characterized by abundant gene expression changes, which cannot be explained by genetic alterations alone. Chromatin data are still limited for this disease, so we used 3627 SE elements from public domain data for closely related tissues, including normal and tumor lung, and cervical cancer cell lines. We integrated the available DNA methylation and gene expression data for HPV + OPSCC samples to filter the candidate SEs to identify functional SEs and their affected targets, which are essential for cancer development. Overall, we found 159 differentially methylated SEs, including 87 SEs that actively regulate expression of 150 nearby genes (211 SE-gene pairs) in HPV + OPSCC. Of these, 132 SE-gene pairs were validated in a related TCGA cohort. Pathway analysis revealed that the SE-regulated genes were associated with pathways known to regulate nasopharyngeal, breast, melanoma, and bladder carcinogenesis and are regulated by the epigenetic landscape in those cancers. Thus, we propose that gene expression in HPV + OPSCC may be controlled by epigenetic alterations in SE elements, which are common between related tissues. Our pipeline can utilize a diversity of data inputs and can be further adapted to SE analysis of diseased and non-diseased tissues from different organisms.