Project description:TRIM59 is a protein that is highly expressed in a variety of tumors and promotes tumor development. However, the use of TRIM59 as tumor diagnosis and prognosis biomarker has not been fully explored. We collected datasets from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) to investigate its potential as a biomarker for diagnosis and prognosis. A total of 46 studies, including 11,558 patients were included in this study. Here, we showed that TRIM59 was significantly upregulated in 15 type of human solid tumors in comparison to their adjacent tissues. Receiver operating characteristic curve (ROC) results provided further evidence for the use of TRIM59 as a potential tumor diagnosis biomarker. Overall survival (OS) was compared between TRIM59 high expression and low expression groups. High expression of TRIM59 indicated a poor prognosis in multiple solid tumors. Taken together, these analyses showed that TRIM59 was upregulated in various types of tumors and had the potential to be used as a diagnostic and prognostic biomarker in human solid tumors.
Project description:IntroductionExosomal microRNAs (miRNAs) play an essential role in near and distant intercellular communication and are potential diagnostic and prognostic biomarkers for various cancers. This study focused on evaluation of exosomal miR-2276-5p in plasma as a diagnostic and prognostic biomarker for glioma.MethodsPlasma exosomes from 124 patients with glioma and 36 non-tumor controls were collected and subjected to quantitative real-time polymerase chain reaction (qRT-PCR) analysis for the exosomal miR-2276-5p expression. Bioinformatic analyses were performed to identify a gene target, and CGGA and TCGA databases were checked for evaluation of prognostic relevance.ResultsThe exosomal miR-2276-5p in glioma patients had a significantly decreased expression, compared with non-glioma patients (p < 0.01). Receiver operating characteristics (ROC) curve analyses were observed to regulate the diagnostic sensitivity and specificity of miR-2276-5p in glioma; the area under the curve (AUC) for miR-2276-5p was 0.8107. The lower expression of exosomal miR-2276-5p in patients with glioma correlated with poorer survival rates. RAB13 was identified as the target of miR-2276-5p which was high in glioma patients, especially those with higher tumor grades and correlated with poor survival.ConclusionThe circulating exosomal miR-2276-5p is significantly reduced in the plasma of glioma patients, and thus, it could be a potential biomarker for patients with glioma for diagnostic and/or prognostic purposes.
Project description:Biglycan (BGN), a key member of the small leucine-rich proteoglycan family, is an important component of the extracellular matrix. Clinical studies have demonstrated that upregulation of BGN is associated with poor prognosis in patients with various types of solid cancer. The present study analyzed the mRNA expression levels of BGN in various types of solid cancer when compared with that in normal tissues via the Oncomine database. The UALCAN, OncoLnc and Kaplan-Meier Plotter databases were additionally used to evaluate the prognostic values of BGN in patients with solid cancer and co-expression gene analysis was conducted using the protein-protein interaction networks of BGN. The present study observed that the mRNA expression levels of BGN were increased in bladder, brain and central nervous system, breast, colorectal, esophageal, gastric, head and neck, lung, ovarian and 28 subtypes of cancer compared with normal tissues. The increased expression of BGN was identified to be associated with a poor outcome in ovarian and gastric cancer. Based on the co-expression network, BGN was identified as the key gene in a 43-gene network. The present findings of increased expression of BGN in solid tumors and its positive association with poor outcome on patient survival indicate that BGN may serve as a prognostic marker and as a target for novel therapeutics for multiple types of cancer.
Project description:Long non-coding RNA (lncRNA) is important in the study of cancer mechanisms. LINC00520 is located on human chromosome 14q22.3 and is a highly conserved long non-coding RNA. LINC00520 is widely expressed in various tissues. The expression of LINC00520 is regulated by transcription factors such as Sp1, TFAP4, and STAT3. The high expression of LINC00520 is significantly related to the risk of 11 cancers. LINC00520 can competitively bind 10 miRNAs to promote tumor cell proliferation, invasion, and migration. In addition, LINC00520 is involved in the regulation of P13K/AKT and JAK/STAT signaling pathways. The expression of LINC00520 is significantly related to the clinicopathological characteristics and prognosis of tumor patients and is also related to the sensitivity of HNSCC to radiotherapy. Here, this article summarizes the abnormal expression pattern of LINC00520 in cancer and its potential molecular regulation mechanism and points out that LINC00520 can be used as a potential biomarker for cancer diagnosis, prognosis, and treatment.
Project description:IntroductionGliomas are the most common malignant brain tumors, with complicated etiology and poor prognosis. However, there is still a lack of specific biomarkers for the diagnosis, treatment and prognosis assessment for glioma patients. Hence, the purpose of this study was to screen biomarkers for prognostic assessment and therapeutic interventions in gliomas.Material and methodsWe utilized The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases to investigate the role of colony-stimulating factor 3 receptor (CSF3R) in glioma. Data analysis was conducted using R, GEPIA 2, TISCH and DepMap.ResultsCSF3R was up-regulated in glioma and associated with the clinical pathological features of the patients. Kaplan-Meier survival analysis indicated a significant association between the expression of CSF3R and prognosis in patients. Univariate and multivariate Cox analyses revealed that patients with high expression of CSF3R have a worse prognosis, and the expression of CSF3R was an independent prognostic factor in gliomas. The nomogram constructed based on the expression of CSF3R demonstrated lower 1-, 3-, and 5-year overall survival (OS) in patients with high CSF3R expression. The biological functional analysis of CSF3R demonstrated its association with various immune regulatory signals. Furthermore, CSF3R was linked to the expression of immune checkpoints and resistance to immunotherapy. Notably, CSF3R was predominantly detected in monocytes/macrophages.ConclusionsOur study suggested that CSF3R might potentially function as an independent prognostic factor for glioma and hold promise as a biomarker and target for immunotherapy in glioma.
Project description:Glioma is one of the most common brain tumors, suggesting the importance of investigating the molecular mechanism of gliomas. We studied the roles of Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in glioma. Expressions of RRM2 are higher in glioma tissues evidenced by TCGA data, western blot and immunohistochemistry. RRM2 is negatively correlated with glioma patient's survival. RNA-seq showed that genes involved in apoptosis, proliferation, cell adhesion and negative regulation of signaling were up-regulated upon RNAi-mediated knock-down of RRM2. Cell phenotypes specific for stably knocking down RRM2 were determined using stable transfection in vitro. In an in vivo model, knock-down of RRM2 inhibited tumor growth and caused suppression of AKT and ERK1/2 signalings. Interfering RRM2 also down-regulated the expression of cyclin A, cyclin B1, cyclin D1, Vimentin, and N-cadherin, and elevated E-cadherin expression. Moreover, overexpression of RRM2 failed to increase the expression of cyclin B1, cyclin D1, and N-cadherin when phosphorylation of AKT and ERK1/2 was suppressed by LY294002 or PD98059. These findings indicated that RRM2 is a positive regulator of glioma progression which contributes to the migration and proliferation of glioma cells through ERK1/2 and AKT signalings and might be a novel prognostic indicator for glioma patients.
Project description:Triple-negative breast cancer (TNBC), which is the most malignant subtype of breast cancer (BC), accounts for 10%-20% of all BC cases. TNBC, which occurs more frequently in young women, is characterized by high rates of cell proliferation and metastasis and poor prognosis. Chemotherapy is the primary systemic therapeutic strategy for TNBC. However, chemotherapy is largely unsuccessful, and effective targeted therapies for TNBC have not been established. Therefore, it is a matter of great urgency to identify precise molecular targets for the promising prognosis of patients with TNBC. Circular RNAs (circRNAs), which are a type of non-coding RNAs (ncRNAs), are abundantly expressed in the eukaryotic cells and exhibit diverse cellular functions. The roles of circRNAs are to sponge microRNA or RNA-binding proteins, regulate gene expression, and serve as templates for translation. Here, we review the current findings on the potential of circRNAs as a diagnostic, prognostic, and therapeutic biomarker for TNBC. However, further studies are essential to elucidate the functions of circRNAs in TNBC. This review also discusses the current limitations and future directions of TNBC-associated circRNAs, which can facilitate the translation of experimental research into clinical application.
Project description:PurposeThere are no satisfactory diagnostic biomarkers for sepsis. Accordingly, this study screened biomarkers valuable for sepsis diagnosis and prognosis using data-independent acquisition (DIA) combined with clinical data analysis.Patients and methodsSerine protease inhibitor Kazal-type 1 (SPINK1) is a differentially expressed protein that was screened using DIA and bioinformatics in sepsis patients (n = 22) and healthy controls (n = 10). The plasma SPINK1 levels were detected using an enzyme-linked immunosorbent assay (ELISA) in an expanded population (sepsis patients, n = 52; healthy controls, n = 10). The diagnostic value of SPINK1 in sepsis was evaluated using receiver operating characteristic (ROC) curve analysis based on clinical data. The prognostic value of SPINK1 for sepsis was evaluated using correlation and survival analyses.ResultsDIA quality control identified 78 differential proteins (72 upregulated and six downregulated), among which SPINK1 was highly expressed in sepsis. The ELISA results suggested that SPINK1 expression was significantly elevated in the sepsis group (P < 0.05). ROC analysis of SPINK1 yielded an area under the curve (AUC) of 0.9096. Combining SPINK1 with procalcitonin (PCT) for ROC analysis yielded an AUC of 1. SPINK1 expression was positively correlated with the Sequential Organ Failure Assessment (SOFA) score (r = 3497, P = 0.0053) and APACHE II score (r = 3223, P = 0.0106). High plasma SPINK1 protein expression was negatively correlated with the 28-day survival rate of patients with sepsis (P = 0.0149).ConclusionThe plasma of sepsis patients contained increased SPINK1 protein expression. Combining SPINK1 with PCT might have a high diagnostic value for sepsis. SPINK1 was associated with the SOFA score, APACHE II score, and the 28-day survival rate in patients with sepsis.
Project description:The TERT promoter (pTERT) mutations, C228T and C250T, play a significant role in malignant transformation by telomerase activation, oncogenesis and immortalisation of cells. C228T and C250T are emerging as important biomarkers in many cancers including glioblastoma multiforme (GBM), where the prevalence of these mutations is as high as 80%. Additionally, the rs2853669 single nucleotide polymorphism (SNP) may cooperate with these pTERT mutations in modulating progression and overall survival in GBM. Using liquid biopsies, pTERT mutations, C228T and C250T, and other clinically relevant biomarkers can be easily detected with high precision and sensitivity, facilitating longitudinal analysis throughout therapy and aid in cancer patient management.In this review, we explore the potential for pTERT mutation analysis, via liquid biopsy, for its potential use in personalised cancer therapy. We evaluate the relationship between pTERT mutations and other biomarkers as well as their potential clinical utility in early detection, prognostication, monitoring of cancer progress, with the main focus being on brain cancer.
Project description:BackgroundShort stature homeobox 2 (SHOX2) is significant gene in the development and progression of multiple types of tumors. Nonetheless, the biological role of SHOX2 within pan-cancer datasets has not been investigated. Thus, comprehensive bioinformatics analyses of pan-cancer datasets were conducted to explore how SHOX2 regulates tumorigenesis.MethodsA variety of tumor datasets and online analytical tools, including SangerBox, TIMER2, LinkedOmic, GEPIA2 and cBioPortal, were applied to explore SHOX2 expression in various tumors. To ascertain the connections between SHOX2 expression and genetic alterations, SHOX2-related genes and tumor immunity, the pan-cancer datasets were examined. In vitro assays were applied to verify the biological functions of SHOX2 in glioma cells via CCK-8, wound healing, Transwell and colony formation assays.ResultsAnalyses found that SHOX2 was overexpressed in multiple cancer types. SHOX2 expression level was significantly correlated with isocitrate dehydrogenase (IDH), 1p/19q, O6-methylguanine DNA methyltransferase (MGMT) status and new types of glioma patients. High mRNA expression levels of SHOX2 were associated with a poor prognosis in multiple tumor patients. KEGG enrichment analysis showed that SHOX2-related genes were associated with cell cycle and DNA damage repair. Genetic alterations of SHOX2 were identified in multiple types of cancers, including duplications and deep mutations. Immune analysis showed that SHOX2 was closely correlated with the tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen and neoantigens and immune checkpoint (ICP) in a variety of tumors and could influence the immunotherapy sensitivity of cancers. CCK-8, wound healing, Transwell and colony formation experiments showed that SHOX2 knockdown inhibited glioma cell proliferation, migration, invasion and colony formation abilities.ConclusionSHOX2 was overexpressed in multiple cancer types in TCGA cohort. SHOX2 knockdown inhibited glioma cell proliferation, migration and colony formation ability. Our study showed that SHOX2 may be an immunotherapeutic and promising prognostic biomarker in certain types of tumors.