Cancer Prognostic Biomarkers Research Articles

A pan-cancer analysis ofWnt family member 7Bin human cancers.

Previous studies have highlighted the crucial role of Wnt7B in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of Wnt7B is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of Wnt7B as a diagnostic or prognostic cancer biomarker has not been fully explored. In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of Wnt7B in cancerous and adjacent noncancerous tissues across a range of tumors. Our data indicate that Wnt7B may serve as a novel prognostic biomarker and therapeutic target in certain cancers. We found significant upregulation of Wnt7B expression levels in the majority of cancer cases examined. Furthermore, Wnt7B can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and Wnt7B expression, which could aid in the development of more precise clinical therapies.

System analysis based on T-cell exhaustion-related genes identifies PTPRT as a promising diagnostic and prognostic biomarker for gastric cancer

Multiple investigations have demonstrated the crucial involvement of T-cell exhaustion (TEX) in anti-tumor immune response and their strong correlation with prognosis. This study aimed at creating a strong signature using TEX for gastric cancer through bioinformatics analysis and experimental validation. We utilized data from The Cancer Genome Atlas (TCGA) databases to retrieve RNA-seq data from patients with stomach adenocarcinoma (STAD). Genes related to TEX were discovered using gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Subsequently, prognostic signature based on TEX was developed using LASSO-Cox analysis. Relationship between key genes and immune cells were examined. Finally, biological function of a key TEX-related gene PTPRT in gastric cancer was verified by in vivo experiment. A total of 29 TEX-related biomarkers were screened by WGCNA and random forest. Among them, five core signatures (PTPRT, CAV2, PPIH, PRDM2, and FGF1), further identified by LASSO-Cox, were considered as strong predictors of prognosis for gastric cancer and associated with immune infiltration. PTPRT gene had the largest number of SNPs, with the most mutation types. In vivo experiments revealed that PTPRT overexpression significantly inhibited tumor malignant progression and accelerated apoptosis through stimulating the secretion of killer cytokines such as TNF-α and IFN-γ. In addition, flow cytometry revealed that PTPRT overexpression alleviated TEX by increasing the abundance of CD8+ T cells, with inhibition of cell surface PD-1 and Tim-3. The predictive prognostic value of TEX gene expression levels was evaluated in patients with gastric cancer, providing a new perspective for precision immuno-oncology studies.

Tracing the evolution of single-cell cancer 3D genomes: an atlas for cancer gene discovery.

Although three-dimensional (3D) genome structures are altered in cancer cells, little is known about how these changes evolve and diversify during cancer progression. Leveraging genome-wide chromatin tracing to visualize 3D genome folding directly in tissues, we generated 3D genome cancer atlases of murine lung and pancreatic adenocarcinoma. Our data reveal stereotypical, non-monotonic, and stage-specific alterations in 3D genome folding heterogeneity, compaction, and compartmentalization as cancers progress from normal to preinvasive and ultimately to invasive tumors, discovering a potential structural bottleneck in early tumor progression. Remarkably, 3D genome architectures distinguish histologic cancer states in single cells, despite considerable cell-to-cell heterogeneity. Gene-level analyses of evolutionary changes in 3D genome compartmentalization not only showed compartment-associated genes are more homogeneously regulated, but also elucidated prognostic and dependency genes in lung adenocarcinoma and a previously unappreciated role for polycomb-group protein Rnf2 in 3D genome regulation. Our results demonstrate the utility of mapping the single-cell cancer 3D genome in tissues and illuminate its potential to identify new diagnostic, prognostic, and therapeutic biomarkers in cancer.

Smartphone-based lateral flow immunoassay for sensitive determination of lactate dehydrogenase at the point of care

Lactate dehydrogenase (LDH), a prevalent enzyme involved in anaerobic glycolysis, is released into body fluids following cell damage and has long been a general marker of tissue injury. However, due to its lack of selectivity and the advent of more accurate biomarkers, the clinical utility of LDH has been largely limited to confirming hemolysis. LDH has been recognized as a valuable prognostic biomarker for various cancers, making its monitoring crucial during cancer management. Traditional LDH methods include spectrophotometric analysis of NADH at 340 nm, native electrophoresis, or enzyme-linked immunosorbent assay. This study presents the first lateral flow immunoassay (LFIA) for the smartphone-based quantification of serum LDH levels at the point of care. Highly-affinity and specific antibodies have been produced, with 5 nM equilibrium dissociation constant and no cross-reactivity with human serum albumin and human immunoglobulin G. Utilizing carbon nanoparticles as signal transducers significantly enhanced the quantification limit 55-fold, compared to the conventional gold nanoparticles-based LFIA, achieving a quantification limit of 1.5 ng mL−1. The developed assay demonstrated a mean recovery rate of 115 ± 21 % when evaluating LDH-spiked serum samples. This method can be an interesting home-testing tool for monitoring cancer progression or therapy effectiveness.

Pan-immune-inflammation value as a prognostic biomarker for colon cancer and its variation by primary tumor location.

A growing body of research indicates significant differences between left-sided colon cancers (LCC) and right-sided colon cancers (RCC). Pan-immune-inflammation value (PIV) is a systemic immune response marker that can predict the prognosis of patients with colon cancer. However, the specific distinction between PIV of LCC and RCC remains unclear. To investigate the prognostic and clinical significance of PIV in LCC and RCC patients. This multicenter retrospective cohort study included 1510 patients with colon cancer, comprising 801 with LCC and 709 with RCC. We used generalized lifting regression analysis to evaluate the relative impact of PIV on disease-free survival (DFS) in these patients. Kaplan-Meier analysis, as well as univariate and multivariate analyses, were used to examine the risk factors for DFS. The correlation between PIV and the clinical characteristics was statistically analyzed in these patients. A total of 1510 patients {872 female patients (58%); median age 63 years [interquartile ranges (IQR): 54-71]; patients with LCC 801 (53%); median follow-up 44.17 months (IQR 29.67-62.32)} were identified. PIV was significantly higher in patients with RCC [median (IQR): 214.34 (121.78-386.72) vs 175.87 (111.92-286.84), P < 0.001]. After propensity score matching, no difference in PIV was observed between patients with LCC and RCC [median (IQR): 182.42 (111.88-297.65) vs 189.45 (109.44-316.02); P = 0.987]. PIV thresholds for DFS were 227.84 in LCC and 145.99 in RCC. High PIV (> 227.84) was associated with worse DFS in LCC [PIV-high: Adjusted hazard ratio (aHR) = 2.39; 95% confidence interval: 1.70-3.38; P < 0.001] but not in RCC (PIV-high: aHR = 0.72; 95% confidence interval: 0.48-1.08; P = 0.114). These findings suggest that PIV may predict recurrence in patients with LCC but not RCC, underscoring the importance of tumor location when using PIV as a colon cancer biomarker.

TIMM9 as a prognostic biomarker in multiple cancers and its associated biological processes

TIMM9 has been identified as a mediator of essential functions in mitochondria, but its association with pan-cancer is poorly understood. We herein employed bioinformatics, computational chemistry techniques and experiments to investigate the role of TIMM9 in pan-cancer. Our analysis revealed that overexpression of TIMM9 was significantly associated with tumorigenesis, pathological stage progression, and metastasis. Missense mutations (particularly the S49L variant), copy number variations (CNV) and methylation alterations in TIMM9 were found to be associated with poor cancer prognosis. Moreover, TIMM9 was positively related with cell cycle progression, mitochondrial and ribosomal function, oxidative phosphorylation, TCA cycle activity, innate and adaptive immunity. Additionally, we discovered that TIMM9 could be regulated by cancer-associated signaling pathways, such as the mTOR pathway. Using molecular simulations, we identified ITFG1 as the protein that has the strongest physical association with TIMM9, which show a promising structural complement.

The roles and mechanisms of coding and noncoding RNA variations in cancer.

Functional variations in coding and noncoding RNAs are crucial in tumorigenesis, with cancer-specific alterations often resulting from chemical modifications and posttranscriptional processes mediated by enzymes. These RNA variations have been linked to tumor cell proliferation, growth, metastasis, and drug resistance and are valuable for identifying diagnostic or prognostic cancer biomarkers. The diversity of posttranscriptional RNA modifications, such as splicing, polyadenylation, methylation, and editing, is particularly significant due to their prevalence and impact on cancer progression. Additionally, other modifications, including RNA acetylation, circularization, miRNA isomerization, and pseudouridination, are recognized as key contributors to cancer development. Understanding the mechanisms underlying these RNA modifications in cancer can enhance our knowledge of cancer biology and facilitate the development of innovative therapeutic strategies. Targeting these RNA modifications and their regulatory enzymes may pave the way for novel RNA-based therapies, enabling tailored interventions for specific cancer subtypes. This review provides a comprehensive overview of the roles and mechanisms of various coding and noncoding RNA modifications in cancer progression and highlights recent advancements in RNA-based therapeutic applications.

NFS1 as a Candidate Prognostic Biomarker for Gastric Cancer Correlated with Immune Infiltrates.

Cysteine desulfurase (NFS1) is closely associated with the occurrence and development of human tumors, but its relationship with the prognosis and immunity of gastric cancer (GC) patients remains unclear. To study the relationship between NFS1 and GC, GC-related data of TCGA were downloaded and analyzed. At the same time, Tumor Immune Estimation Resource (TIMER) and Kaplan‒Meier Plotter were used for relevant online analysis. Clinical samples were collected for immunohistochemical testing to validate the results. The mRNA and protein levels of NFS1 in GC tissues were significantly higher than those in normal tissues. In terms of the operating characteristic curve (ROC), the area under the curve (AUC) was 0.793, indicating that NFS1 had a high diagnostic value for GC. Further analysis showed that NFS1 expression was highly correlated with the depth of tumor invasion, lymph node metastasis, and tumor stage. Survival analysis showed that patients with high expression of NFS1 had a poorer prognosis, and NFS1 was an independent risk factor. Enrichment analysis by GO, KEGG, and GSEA showed that NFS1 was enriched in immune-related pathways. The expression of NFS1 was significantly positively correlated with the proportion of macrophages M0 and plasma cells but negatively correlated with the proportion of B cells memory, monocytes, and mast cells resting. In addition, NFS1 expression was significantly correlated with TMB levels and responses to immunotherapy. Our results suggest that NFS1 may be a potential biomarker for the diagnosis and prediction of prognosis and immunotherapy efficacy in GC.

Circulating miRNA panels as a novel non-invasive diagnostic, prognostic, and potential predictive biomarkers in non-small cell lung cancer (NSCLC)

BackgroundNon-small cell lung cancer (NSCLC) is characterised by its aggressiveness and poor prognosis. Early detection and accurate prediction of therapeutic responses remain critical for improving patient outcomes. In the present study, we investigated the potential of circulating microRNA (miRNA) as non-invasive biomarkers in patients with NSCLC.MethodsWe quantified miRNA expression in plasma from 122 participants (78 NSCLC; 44 healthy controls). Bioinformatic tools were employed to identify miRNA panels for accurate NSCLC diagnosis. Validation was performed using an independent publicly available dataset of more than 4000 NSCLC patients. Next, we correlated miRNA expression with clinicopathological information to identify independent prognostic miRNAs and those predictive of anti-PD-1 treatment response.ResultsWe identified miRNA panels for lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) diagnosis. The LUAD panel consists of seven circulating miRNAs (miR-9-3p, miR-96-5p, miR-147b-3p, miR-196a-5p, miR-708-3p, miR-708-5p, miR-4652-5p), while the LUSC panel comprises nine miRNAs (miR-130b-3p, miR-269-3p, miR-301a-5p, miR-301b-5p, miR-744-3p, miR-760, miR-767-5p, miR-4652-5p, miR-6499-3p). Additionally, miR-135b-5p, miR-196a-5p, miR-31-5p (LUAD), and miR-205 (LUSC) serve as independent prognostic markers for survival. Furthermore, two miRNA clusters, namely miR-183/96/182 and miR-767/105, exhibit predictive potential in anti-PD-1-treated LUAD patients.ConclusionsCirculating miRNA signatures demonstrate diagnostic and prognostic value for NSCLC and may guide treatment decisions in clinical practice.

Clinicopathological and prognostic value of tertiary lymphoid structures in lung cancer: a meta-analysis.

The purpose of this meta-analysis was to examine the clinicopathological and prognostic significance of tertiary lymphocytic infiltrates in lung cancer. A systematic search was performed in many databases, including PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wangfangdate, and CBM, up until January 2024. We calculated the hazard ratio (HR), odds ratios (OR), and confidence interval (CI), and accomplished this meta-analysis with Stata 15 software. 14 studies, including 3101 patients, were subjected to analysis. High TLS detection was associated with a longer OS (HR = 0.545, 95% CI: 0.359-0.827, p = 0.004), DFS (HR = 0.431, 95% CI: 0.350-0.531, p < 0.001), and RFS (HR = 0.430, 95% CI: 0.325-0.569, p < 0.001). Meanwhile, it was observed that a higher detection of TLS was significantly correlated with the administration of adjuvant chemotherapy (OR = 1.505, 95% CI: 1.017-2.225, p = 0.041). Not only that, but there was a higher occurrence of significantly elevated TLS detection in the early N stages (N = 0) compared to the advanced N stages (N = 1, 2, and 3) (OR = 1.604, 95% CI: 1.021-2.521, p = 0.04). Elevated detection of TLS has been observed to be correlated with extended OS, DFS, and RFS in cases of lung cancer. This finding suggests that TLS could potentially serve as a valuable prognostic biomarker for lung cancer.

Circulating Long-Non Coding RNA RP11-445H22.4 as a Diagnostic and Prognostic Biomarker of Breast Cancer

Circulating Long-Non Coding RNA RP11-445H22.4 as a Diagnostic and Prognostic Biomarker of Breast Cancer

Cornulin as a Key Diagnostic and Prognostic Biomarker in Cancers of the Squamous Epithelium.

The prevalence of squamous cell carcinoma is increasing, and efforts that aid in an early and accurate diagnosis are crucial to improve clinical outcomes for patients. Cornulin, a squamous epithelium-specific protein, has recently garnered attention due to its implications in the progression of squamous cell carcinoma developed in several tissues. As an epidermal differentiation marker, it is involved in skin anchoring, regulating cellular proliferation, and is a putative tumor suppressor. The physiologically healthy squamous epithelium displays a considerable level of Cornulin, whereas squamous cell carcinomas have marked downregulation, suggesting that Cornulin expression levels can be utilized for the early detection and follow-up on the progression of these types of cancer. Cornulin's expression patterns in cervical cancer have been examined, and findings support the stepwise downregulation of Cornulin levels that accompanies the progression to neoplasia in the cervix. Additional studies documented a similar trend in expression in other types of cancer, such as cutaneous, esophageal, and oropharyngeal squamous cell carcinomas. The consistent and predictable pattern of Cornulin expression across several squamous cell carcinomas and its correlation with key clinicopathological parameters make it a reliable biomarker for assessing the transformation and progression events in the squamous epithelium, thus potentially contributing to the early detection, definitive diagnosis, and more favorable prognosis for these cancer patients.

Lemur tail kinase 3 serves as a predictor of patient outcomes and a target for the treatment of ovarian cancer

Lemur tail kinase 3 (LMTK3) belongs to a family of tyrosine kinases that are known to correlate with tumor grade and patient survival in some cancers. Here, we validated LMTK3 as a specific target and a prognostic biomarker in ovarian cancer (OC). In samples from 204 stage I-II OC patients, immunohistochemical studies revealed a higher cytoplasmic-to-nuclear staining intensity of LMTK3, which correlated with worse overall survival (p<0.001). Efficacy studies utilizing novel LMTK3 binding peptides (LMTK3BPs) showed that all chemosensitive and chemoresistant OC cells were killed without affecting normal cells (p<0.005), with synergistic effects shown following cisplatin and docetaxel treatment. In an orthotopic xenograft mouse model of OC, we saw a 35% tumor reduction in response to intravenous injections of 2mg/kg LMTK3BP given three times a week for 3weeks. Furthermore, invivo safety studies showed no signs of toxicity after LMTK3BP treatment, even at doses as high as 40mg/kg. This study highlights LMTK3 as a predictor of patient clinical outcomes. More importantly, novel LMTK3BPs represent potential safe treatment options, either alone or in combination with therapies, for OC.

Predicting Pathological Characteristics of HER2-Positive Breast Cancer from Ultrasound Images: a Deep Ensemble Approach.

The objective is to evaluate the feasibility of utilizing ultrasound images in identifying critical prognostic biomarkers for HER2-positive breast cancer (HER2 + BC). This study enrolled 512 female patients diagnosed with HER2-positive breast cancer through pathological validation at our institution from January 2016 to December 2021. Five distinct deep convolutional neural networks (DCNNs) and a deep ensemble (DE) approach were trained to classify axillary lymph node involvement (ALNM), lymphovascular invasion (LVI), and histological grade (HG). The efficacy of the models was evaluated based on accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), receiver operating characteristic (ROC) curves, areas under the ROC curve (AUCs), and heat maps. DeLong test was applied to compare differences in AUC among different models. The deep ensemble approach, as the most effective model, demonstrated AUCs and accuracy of 0.869 (95% CI: 0.802-0.936) and 69.7% in LVI, 0.973 (95% CI: 0.949-0.998) and 73.8% in HG, thus providing superior classification performance in the context of imbalanced data (p < 0.05 by the DeLong test). On ALNM, AUC and accuracy were 0.780 (95% CI: 0.688-0.873) and 77.5%, which were comparable to other single models. The pretreatment US-based DE model could hold promise as a clinical guidance for predicting pathological characteristics of patients with HER2-positive breast cancer, thereby providing benefit of facilitating timely adjustments in treatment strategies.

FN1, a reliable prognostic biomarker for thyroid cancer, is associated with tumor immunity and an unfavorable prognosis.

Thyroid cancer (THCA) is a malignant tumor that affects the endocrine system. At present, an effective treatment for THCA remains elusive, particularly for medullary carcinoma and undifferentiated carcinoma, due to the lack of suitable medications and prognostic markers. Patient RNA-sequencing and clinical data were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Protein-protein interaction analyses were performed for differentially expressed genes related to THCA. Moreover, the associations between fibronectin 1 (FN1), clinical data, immune checkpoint genes and immune cell infiltration was assessed. The potential functional role of the FN1 gene was evaluated through gene set enrichment analysis. Immunohistochemistry was used to assess FN1 expression in 103 cases of THCA, comprising 32 with papillary carcinoma, 30 with follicular carcinoma, 35 with medullary carcinoma and 6 with undifferentiated carcinoma. Finally, 11 co-expression modules were constructed and the expression of five identified hub genes (FN1, mucin-1, keratin 19, intracellular adhesion molecule 1 and neural cell adhesion molecule) were evaluated. The results demonstrated that higher FN1 gene expression levels were strongly associated with a higher pathologic stage and tumor stage, and were significantly associated with immune cell infiltration in THCA. Significant increases in FN1 protein expression levels were noted among patients diagnosed with four types of THCA, comprising papillary carcinoma, follicular carcinoma, medullary carcinoma and undifferentiated carcinoma. Patients diagnosed with medullary carcinoma and undifferentiated carcinoma, and with low FN1 expression levels, exhibited a significant survival advantage compared with those with high FN1 expression levels. In conclusion, the present study identified five hub genes involved in the onset and progression of THCA. Furthermore, FN1 could serve as a candidate biomarker and a therapeutic target for THCA and may be a key gene mediating THCA immune infiltration.

MicroRNA profile of endometrial cancer from Indian patients-identification of potential biomarkers for prognosis

Endometrial cancer is one of the major cancers in women throughout the world. If diagnosed early, these cancers are treatable and the prognosis is usually good. However, one major problem in treating endometrial cancer is accurate diagnosis and staging. Till date, the choice method for diagnosis and staging is histopathology. Although there are few molecular markers identified, they are not always sufficient in making accurate diagnosis and deciding on therapeutic strategy. As a result, very often patients are under treated or over treated. In this study, our group has profiled microRNAs from Indian patients using NGS-based approach. We have identified 212 differentially expressed microRNAs in endometrial cancer. Among these, there are 17 novel miRNAs. Since this data represents only Indian cohort and also lacks survival data, validation across other populations is necessary before being considered as biomarkers. As one approach towards this, these microRNAs have also been compared to data from TCGA, which represent other populations and also correlated to relevance in overall survival. Using in-silico approaches, mRNA targets of the miRNAs have been predicted. After comparing with TCGA, we have identified 16 miRNA-mRNA pairs which could be potential prognostic biomarkers for endometrial cancer. This is the first miRNA profiling report from Indian cohort and one of the very few studies which have identified potential biomarkers of prognosis in endometrial cancer.

Clinicopathological and prognostic role of CEP55 expression in cancer patients: A meta‐analysis of 31 studies with 12,543 patients

AbstractBackgroundDysregulated expression of centrosomal protein 55 (CEP55) has been detected in multiple types of cancers. However, the clinical value of CEP55 expression in cancer is controversial. The current meta‐analysis quantitatively investigated the association between CEP55 expression and prognostic outcomes in cancers.MethodsA literature search was performed using the Chinese National Knowledge Infrastructure (CNKI), Wanfang databases, Web of Science, Embase, MEDLINE, PubMed, and Cochrane Library for primary studies. The pooled hazard ratios (HRs) and odds ratios (ORs) were used to investigate the association between CEP55 expression and its prognostic and clinicopathological value in cancers.ResultsA total of 12,543 patients from 31 studies were included in this meta‐analysis. High CEP55 expression was significantly associated with poor differentiation, deeper tumor invasion and increased lymph node metastasis in cancer patients. The pooled results indicated that elevated CEP55 expression can predict a poor overall survival (OS) and disease‐free survival (DFS) in cancers. These results should be interpreted with caution because of publication bias. However, the pooled HR for OS of lung cancers was 1.50 (95% CI = 1.36–1.67, p &lt; 0.01) with no heterogeneity and publication bias.ConclusionsCEP55 overexpression correlated with poor cancer differentiation, deeper tumor invasion, and increased lymph node metastasis, suggesting that CEP55 may serve as a predictive and prognostic biomarker for cancers, especially for lung cancers.

Construction of CeRNA Regulatory Network Based on WGCNA to Reveal Potential Prognostic Biomarkers for AML Cancer

Background: Acute myeloid leukemia (AML) is a type of blood cancer with diverse genetic pathogenesis. The identification of potential molecular biomarkers could improve the AML diagnosis and targeted therapy. Recently, competing endogenous RNAs (ceRNAs) became an active area in cancer research to determine molecular mechanisms underlying tumor development. Objectives: The aim of the present study was to investigate the key molecular biomarkers that are closely related to AML through bioinformatics analysis. Methods: In this research, the RNA-seq data of 151 AML patients and 151 corresponding health samples were retrieved from The Cancer Genome Atlas (TCGA) database and GTEx Portal (genotype-tissue expression), respectively. After that we screened the differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs by “limma” package in R to construct the co-expression network ceRNA (miRNA-lncRNA-mRNA) with weighted gene co-expression network analysis (WGCNA) package in R and Cytoscape (version 3.7.2) software, respectively. Then the relevant modules were identified and functional enrichment analysis was used to uncover the modules that are biologically related to AML cancer. Results: Based on our bioinformatics studies, we constructed a significant module which contain 333 genes. Among them, five up-regulated miRNAs with the highest GS (gene significant), include hsa-miR-374B, hsa-miR-553, hsa-miR-3679, hsa-miR-548L, hsa-miR-597 and five down-regulated miRNAs with the lowest GS including hsa-miR-3934, hsa-miR-4746, hsa-miR-466, hsa-miR-6722, hsa-miR-4490. For protein-coding genes (PCGs), the top-five up-regulated PCGs with the highest GS were AMIGO3, H2AC17, SPACA5, GPR21, and OR13C3. The top-five down-regulated PCGs with the lowest GS were XBP1, TOMM6, TREX1, TNFRSF6B, and BOLA2. Among the lncRNAs, the five up-regulated lncRNAs with the highest level of GS were GREP1, ZBTB20-AS2, LINC01596, LINC00345, and RMRP. The five down-regulated lncRNAs with the lowest GS were LINC01609, LINC01707, LINC02270, LINC02309, and LINC02243. These lncRNAs can serve as potential biomarkers to distinguish between AML and normal samples. Conclusions: Finally, considering the role of ceRNA network in various biological processes, examining the role of ceRNAs in AML may provide a deeper insight into molecular mechanisms underlying the pathogenesis of cancer. This understanding may propose potential biomarkers for diagnosis and therapeutic interventions.

Telomerase related molecular subtype and risk model reveal immune activity and evaluate prognosis and immunotherapy response in prostate cancer

BackgroundProstate cancer ranks among the six most lethal malignancies worldwide. Telomerase, a reverse transcriptase enzyme, plays a pivotal role in extending cellular telomeres and is intimately associated with cell proliferation and division. However, the interconnection between prostate cancer and telomerase-related genes (TEASEs) remains unclear.MethodsSomatic mutations and copy number alterations of TEASEs were comprehensively analyzed. Subsequently, the transcripts of prostate cancer patients in TCGA and GEO databases were integrated to delineate new molecular subtypes. Followed by constructing a risk model containing nine characteristic genes through Lasso regression and Cox prognostic analysis among different subtypes. Various aspects including prognosis, tumor microenvironment (TME), landscape of immunity, tumor mutational burden (TMB), stem cell correlation, and median inhibitory concentration amongst different risk groups were compared. Finally, the expression, prognosis, and malignant biological behavior of ZW10 interactor (ZWINT) in vitro was explored.ResultsTEASEs exhibited a notably high mutation frequency. Three distinct molecular subtypes and two gene subclusters based on TEASEs were delineated, displaying significant associations with prognosis, immune function regulation, and clinical characteristics. Low-risk patients demonstrated superior prognosis and better response to immunotherapy. Conversely, high-risk patients exhibited higher TMB and stronger stem cell correlations. It was also found that the patients’ sensitivity to chemotherapy agents was impacted by the risk score. Finally, ZWINT’s potential as a novel diagnostic and prognostic biomarker for prostate cancer was validated.ConclusionsTEASEs play a pivotal role in modulating immune regulation and immunotherapeutic responses, thereby significantly impacting the diagnosis, prognosis, and treatment strategies for affected patients.

IFITM10 Enhance Tumor Angiogenesis and Promotes Cancer Progression through STAT3 Activation.

Humankind have been struggling with colorectal cancer (CRC) for long period with its rapid progression and invasive metastasis. By hyperactivating IL-6/STAT3 signaling, CRC facilitates the capacity of angiogenesis to plunder massive nutrients and develops gradually under harsh condition. The Cancer Genome Atlas database was analyzed for acquiring interferon-γ inducible protein 10 (IFITM10) expression levels and their correlation with clinical outcomes. The cell angiogenic ability were assessed by Cell Counting Kit-8 (CCK-8) and tube formation assay. Immunofluorescence, Western blot, and enzyme-linked immunosorbent assay (ELISA) assay were using to assess potential mechanism. In our study, we find that IFITM10 is upregulated in CRC and is positively related with tumor angiogenesis. We also find that IFITM inhibition decreased STAT3 phosphorylation level and IFITM10-mediated angiogenesis depends on STAT3 activation. Furthermore, our data suggests that IFITM10 may be a key prognostic biomarker in colorectal cancer. Together, our study suggests that IFITM10 enhance angiogenesis through STAT3 activation during CRC progression, which highlighting its potency as a therapeutic target for colorectal cancer.