PurposeVenous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a leading cause of morbidity and mortality in cancer patients. Prostate cancer is associated with an elevated risk of VTE, yet the molecular drivers remain poorly defined.MethodsIn this study, we employed high-throughput proteomic profiling using the SomaLogic platform to analyze plasma from 85 prostate cancer patients, including 43 with and 42 without VTE. Samples were collected at cancer diagnosis, with VTE diagnosed at a mean of 96.8 months later.ResultsPrincipal component analysis showed modest proteomic separation between groups. Differential expression analysis identified enriched pathways in VTE patients, including hemostasis (TIMP1, JAM2, TMX3, F3, and ESAM), cell adhesion (CXCL12, CCL11, CCN5, COL18A1, and ADGRB1) and cell proliferation (TIMP1, REG1B, REG1A, CRLF2, and ALDH1A2). Receiver Operating Characteristic analysis using top fifteen proteins achieved an area under the curve of 0.859, indicating strong predictive value for VTE in this cohort.ConclusionsWe identified a specific cluster of circulating proteins associated with development of VTE in patients with prostate cancer. This work deepens understanding of systemic mediators of cancer-associated VTE and, pending validation in other cohorts, paves the way for improved risk stratification and long-term monitoring in this population.

BackgroundHepatocellular carcinoma (HCC) is a major global health burden, with limited tools for early diagnosis and prognosis. This study explores serum-derived exosomal miR-1275 as a potential non-invasive biomarker for HCC.MethodsExosomes were isolated from serum samples of 50 HCC patients and 50 matched healthy controls. miR-1275 expression was quantified by qRT-PCR and compared with traditional biomarkers (AFP, CEA, CA199, DCP, AFP-L3%). Diagnostic performance was evaluated using ROC curves. Bioinformatic analyses, including TCGA pan-cancer data, target gene prediction, and pathway enrichment, were performed to explore regulatory mechanisms.ResultsExosomal miR-1275 levels were significantly reduced in HCC patients and correlated with advanced clinical stage, tumor burden, and metastasis. miR-1275 showed strong diagnostic value (AUC = 0.869), outperforming CEA and CA199, and improved significantly when combined with other biomarkers (AUC = 0.982). UBE2V1 was identified as a key miR-1275 target involved in cancer-related pathways, including ubiquitination and mTOR signaling.ConclusionSerum exosomal miR-1275 is a promising biomarker for early diagnosis and prognosis of HCC. Its integration into multimarker panels could enhance clinical decision-making and patient management.

Diagnosing papillary thyroid carcinoma (PTC) remains challenging, particularly due to limitations in fine-needle aspiration biopsy (FNAB), which yields up to 10% nondiagnostic results. The objective of this study was to evaluate the diagnostic and prognostic potential of four candidate microRNAs (miR-21, miR-31, miR-187-3p, and miR-200a-5p) in PTC from multinodular goiter (MNG) and normal. Fresh tissue samples from PTC and MNG patients were analyzed using quantitative RT-PCR, followed by ROC analysis to assess diagnostic accuracy and correlation with clinical, histopathological, and hormonal parameters. Compared to normal tissue, miR-21 and miR-187-3p were significantly upregulated in PTC, while miR-31 and miR-200a-5p were downregulated. MNG samples showed similar but less pronounced trends. All four miRNAs differed significantly between PTC and MNG. ROC analysis revealed strong diagnostic performance, particularly for miR-187-3p (AUC = 0.937) and miR-21 (AUC = 0.914), with their combination achieving an AUC of 0.968. Expression levels correlated with age, tumor stage, surgical status, and thyroid hormones (TSH, ATG, TG), highlighting novel regulatory patterns. This miRNA panel offers promising diagnostic value and insight into PTC pathogenesis, suggesting potential for non-invasive diagnostics and targeted therapies.

BackgroundCD137L plays a substantial role in immune regulation and has been associated with tumor progression. However, its expression pattern and clinical significance in colorectal cancer remain unclear. The current study was planned to evaluate the expression levels of CD137L in colorectal cancer tissues and investigate its association with clinicopathological characteristics and patient survival.Methodology36 tissue samples were collected from colorectal cancer patients followed by RNA extracted. Following the cDNA synthesis, qRT-PCR was conducted to evaluate the CD137L expression, normalized against GAPDH and the comparative expression was determined using the ΔΔCt method. Chi-square test was applied to evaluate the relation of CD137L expression with clinical parameters. Meanwhile, the TCGA database was explored to find the relationship between the prognosis of colorectal cancer patients and different levels of CD137L expression and to analyze the distribution characteristics of differentially expressed genes.ResultsCD137L expression was significantly correlated with patient survival (P < 0.05), with higher expression observed in patients who were alive at the time of analysis. Clinical parameters such as age and gender were insignificantly associated (P > 0.05) with CD137L expression. However, a significant correlation (P = 0.03) was noted between CD137L expression and tumor staging, suggesting its potential involvement in CRC progression. Furthermore, Analysis of TCGA data showed that patients with elevated CD137L expression exhibited improved overall survival compared to those with lower expression levels. Enrichment analysis revealed that CD137 was primarily enriched with immune cell proliferation, T cell activation and Th1/Th2 balance-related signaling pathways.ConclusionCD137L may serve as a reliable indicator for forecasting the outcome of colorectal cancer patients, providing guidance for colorectal cancer prognosis.

BackgroundAutoantibodies against tumor-associated antigens (TAAs) are promising noninvasive cancer biomarkers due to their specificity and stability. Gastric cancer (GC) diagnosis often requires invasive procedures, emphasizing the need for reliable blood-based biomarkers.ObjectiveThis study assessed whether serum IgG and IgA autoantibodies, individually or combined, could serve as noninvasive biomarkers for gastric cancer.Experimental designWe analyzed 27 autoantibodies in serum from 265 healthy controls, 296 GC patients, and 195 gastritis patients using protein microarray. Autoantibody levels and the IgG/IgA ratio were calculated. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves.ResultsWe identified 24 differentially expressed autoantibodies (DEAs) for IgA and 17 for IgG between GC patients and controls. In distinguishing GC from gastritis, 20 DEAs for IgA and 23 for IgG were significant. The IgG/IgA ratio of MIP1 beta had the highest diagnostic performance between atrophic gastritis and GC, while MMP7 was the most effective between chronic gastritis and GC. The gbm model with 14 autoantibodies had the highest Youden's index for GC versus controls, and a 13-autoantibody model performed best for GC versus all gastritis.ConclusionsSpecific panels of autoantibodies could serve as noninvasive diagnostic tools for distinguishing GC from controls and gastritis.

BackgroundGastric cancer is the fifth most common malignancy and third leading cause of cancer death in China, with advanced-stage five-year survival below 20%. βIII-tubulin (TUBB3) is overexpressed in cancers but its role in gastric cancer remains unclear.MethodsTUBB3 expression was analyzed using TCGA data and clinical samples. Knockdown models assessed its effects on proliferation, migration, and invasion in vitro and in vivo.ResultsTUBB3 was significantly upregulated in gastric cancer tissues versus normal mucosa. High TUBB3 correlated with poorer disease-free and overall survival but not other clinicopathological features. Functionally, TUBB3 knockdown inhibited proliferation via G2/M arrest and reduced migration/invasion by disrupting invadopodia, without affecting apoptosis, EMT, or ECM degradation. In vivo, TUBB3 depletion suppressed tumor growth and metastasis. Mechanistically, TUBB3 promoted G2/M transition via p21/Cyclin B1 and enhanced invasiveness through Cortactin/JNK activation.ConclusionTUBB3 overexpression predicts poor prognosis in gastric cancer. It drives proliferation via cell cycle regulation and metastasis through invadopodia formation, suggesting its potential as a therapeutic target.

BackgroundThe CD155-TIGIT axis, a breast cancer progression biomarker, underscored neoadjuvant chemotherapy (NAC) response variability in triple-negative breast cancer (TNBC), urging biomarker-based patient stratification for timely therapy.MethodsThirty-nine TNBC patients who received NAC were recruited. The expression of TIGIT, CD155, CD226, and CD96 on tumoral and stromal cells in the tumor microenvironment was detected by immunohistochemistry, and their relationships with NAC response were explored.Results10.3% patients exhibited grade 1 (G1) response to NAC, and 20.5% achieved a complete pathological response. Notably, CD155 and CD96 were predominantly detected on tumor cells, whereas CD226 and TIGIT were predominantly detected on stromal cells. The expression of these markers did not significantly correlate with response to NAC ( > 0.05), and each individual marker lacked predictive power for determining NAC therapeutic efficacy ( > 0.05). However, a specific combination of tumoral cells expression of CD226(≥4%), CD155(≥40%), and CD96(≥35%), coupled with TIGIT expression on tumoral (<35%) and stromal cells (<12.5%), was able to identify patients with G1 response to NAC.ConclusionExpression levels of TIGIT/CD155/CD226/CD96 on tumoral and stromal cells might collectively serve as predictive biomarkers for NAC response in TNBC. This implied that CD155-TIGIT axis could be prospectively applied clinically to identify NAC-resistant TNBC patients.

BackgroundHomeobox C6 (HOXC6) shows abnormal expression in various tumors, but its pattern in lung squamous cell carcinoma (LUSC) remains unclear.ObjectiveTo investigate HOXC6's expression and function in LUSC.MethodsHOXC6 expression was analyzed using single-cell RNA sequencing (scRNA-seq) in LUSC, cervical squamous cell carcinoma (CESC), esophageal squamous cell carcinoma (ESCC), laryngeal squamous cell carcinoma (LSCC), and oral squamous cell carcinoma (OSCC), verified by RNA-seq and immunohistochemistry (IHC). CRISPR knockdown assessed proliferation impact. Immune infiltration analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses explored immune microenvironment relationships.ResultsHOXC6 was highly expressed in LUSC (standard mean difference (SMD) = 1.17, confidence interval (CI) = 0.75-1.59, area under the curve (AUC) = 0.88), confirmed by IHC (P = 1.6e-10, AUC = 0.99). HOXC6 silencing inhibited proliferation. High expression negatively correlated with immune infiltration and decreased StromalScore, ImmuneScore, and ESTIMATEScore. HOXC6 was elevated in other squamous carcinomas.ConclusionHigh HOXC6 expression may promote LUSC and pan-squamous carcinoma development through mitosis regulation.

BackgroundMelanoma represents one of the most aggressive skin cancers, responsible for over 75% of skin cancer-related deaths despite comprising only 5% of cases. Despite therapeutic advances, patient responses remain variable and unpredicv. The Signaling Lymphocytic Activation Molecule (SLAM) family regulates immune cell communication, with SLAMF8 being predominantly expressed on myeloid cells. However, SLAMF8's specific role in melanoma pathogenesis remains largely unexplored.MethodsIn this retrospective integrative study, we systematically investigated SLAMF8's role in melanoma through multi-omics analyses using TIMER, GEPIA, and UALCAN databases, following the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for observational data reporting. Functional studies were conducted in A-375 and SK-MEL-28 melanoma cell lines using siRNA-mediated knockdown, followed by migration, invasion, and proliferation assays. DNA methylation patterns were analyzed via the SMART database, while mutation profiles were examined using cBioPortal and COSMIC. Immune infiltration analysis was performed through TIMER, and pathway associations were investigated using Gene Set Enrichment Analysis and protein-protein interaction networks. Finally, two-sample Mendelian Randomization analysis assessed the causal relationship between SLAMF8 expression and melanoma susceptibility.ResultsSLAMF8 expression was significantly higher in metastatic melanoma compared to primary tumors, with expression patterns varying across disease stages and between sexes. Higher SLAMF8 expression correlated with improved disease-free and overall survival. Functional studies demonstrated that SLAMF8 knockdown significantly enhanced melanoma cell proliferation, migration, and invasion. DNA methylation analysis revealed significant negative correlations between methylation at specific CpG sites and SLAMF8 expression, with hypermethylation associated with worse survival outcomes. Mutation analysis identified alterations in 10.21% of melanoma patients. Immune infiltration studies demonstrated strong correlations between SLAMF8 expression and enhanced immune cell presence. GSEA linked SLAMF8 to critical immune pathways including allograft rejection, inflammatory response, and interferon signaling. Mendelian Randomization analysis established a protective causal relationship between SLAMF8 and melanoma risk (OR = 0.39, 95% CI = 0.21-0.74, p = 3.34e-03).ConclusionOur study demonstrates that SLAMF8 plays a critical role in melanoma by suppressing tumor progression and modulating the immune microenvironment. Elevated SLAMF8 expression in metastatic melanoma is associated with improved patient survival, suggesting its utility as a prognostic biomarker. Furthermore, its tumor-suppressive effects and immune-regulatory functions highlight SLAMF8 as a promising therapeutic target for melanoma treatment strategies.

BackgroundImmune-inflammatory responses and dysregulation play a key role in liver fibrosis (LF) and cirrhosis progression, but the phenotypic and functional dynamics of immune cell populations remain poorly characterized.MethodsLF-related data from the GEO database were analyzed using ssGSEA to quantify immune cell infiltration and Kaplan-Meier analysis to assess the prognostic value of specific immune cell populations. Single-cell RNA sequencing data were used to establish an immune cell atlas, identify cell types linked to poor prognosis, and validate characteristic genes. Additionally, the functional distinctions and cell-cell interactions were further investigated.ResultsLF patients showed increased infiltration of monocytes, T cells, and NK cells, associated with poor outcomes. Genes linked to poor prognosis were markedly expressed in mononuclear phagocytes, T cells, and innate lymphoid cells (ILCs), which were further classified into 24 distinct subpopulations. Pro-fibrotic scar-associated macrophages and pro-inflammatory ILCs increased, while anti-inflammatory Kupffer cells and protective ILCs decreased. CCR7-expressing T cells and depletion-related genes were elevated in peripheral blood mononuclear cells, with ILCs showing increased expression of S1PR4 and S1PR5. Furthermore, macrophages expressing CD9 and IGFBP7 were identified.ConclusionThis study highlights immune heterogeneity in LF, identifying key cell populations linked to disease progression, offering potential immunotherapy targets.

BackgroundLung cancer remains a leading cause of cancer-related mortality, with accurate staging essential for guiding treatment. Advances in next-generation sequencing (NGS) and machine learning (ML) enable more precise classification, improving on traditional imaging-based methods.ObjectiveThis retrospective study applies XGBoost with cross-validation (CV) to classify early vs. late-stage lung cancer using RNA-Seq data from 993 patients in The Cancer Genome Atlas (TCGA) cohort.MethodsGene selection was conducted using the Wilcoxon rank-sum test on training data, and the XGBoost model was optimized via cross-validation. Model performance was assessed using the Area Under the Curve (AUC), with sensitivity-specificity analysis across classification thresholds.ResultsThe XGBoost model achieved a test AUC of 0.6534, identifying 40 key genes that optimize predictive accuracy while minimizing overfitting. Thresholds of 0.3 and 0.4 were optimal, balancing sensitivity and specificity for clinical applicationConclusionsIntegrating RNA-Seq data with machine learning improves lung cancer staging accuracy. Future research should focus on dataset expansion, model benchmarking, and multi-omics integration to enhance clinical applicability.

PurposeThis study aimed to compare tumour microbiota characteristics as potential recurrence predictors in estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) breast cancer.MethodsFormalin-fixed paraffin-embedded (FFPE) tumour tissues were obtained from 52 patients with ER + PR + breast cancer, and patients were retrospectively followed up for over 7 years. Patients were categorized into three groups: local recurrence (n = 13), distant metastasis (n = 17), and no recurrence (n = 22). Gene expression profiles and microbial activity in tumour tissues were analyzed by microarray and 16S rRNA sequencing, respectively, from the same total RNA extracted from FFPE samples.ResultsCompared to nonrecurrent tumours, the ratio of strict anaerobic bacteria to aerobic bacteria activity was significantly upregulated in tumours with local recurrence, while no significant difference was observed in the distant metastasis group. Furthermore, the activity ratio showed a significant correlation with the cancer relating genes expression of , and three small nuclear RNAs across all 52 tumours.ConclusionThis study provided the first evidence of distinctive features of tumor-associated microbiota in ER+/PR + breast cancer patients with local recurrence, suggesting their potential as predictive biomarker for local recurrence. However, these findings require further validation in larger cohorts due to the limited sample size.

BackgroundGastric cancer is the 4th most common and 3rd deadliest cancer worldwide. Research has shown that PDCD2-like (PDCD2L) is elevated in several tumors.ObjectiveTo explore the relationship between PDCD2L expression and gastric cancer prognosis and its function in gastric cancer.MethodsImmunohistochemical staining and immunoblotting were performed to examine the expression of PDCD2L. The effect of PDCD2L on gastric cancer cells were evaluated by a series of in vitro cellular function experiments and in vivo proliferation experiments.ResultsPDCD2L was found to be overexpressed in gastric cancer tissues compared to non-tumor tissues, and its higher levels were associated with worse prognosis. In vitro experiments showed that reducing PDCD2L expression in gastric cancer cells led to decreased proliferation, migration, and invasion, with a similar effect observed in animal models. Knockdown of PDCD2L also resulted in lower expression of cell cycle- and motility-related proteins, while upregulation of PDCD2L had the opposite effect. Additionally, NGS analysis revealed that PDCD2L knockdown reduced the expression of RFX1, a gene linked to cell proliferation and migration, suggesting that PDCD2L and RFX1 together promote cancer progression.ConclusionPDCD2L could serve as a biomarker for gastric cancer prognosis and a potential therapeutic target.

IntroductionImmunotherapy benefits gastrointestinal tumor patients. But traditional biomarkers like TMB and MSI can't precisely identify beneficiaries. Phosphatidylinositol - 3,4,5 - triphosphate - dependent Rac exchange factor 2 (PREX2) plays a complex role in tumorigenesis.MethodsIn a retrospective study of 1764 patients (1385 colorectal, 379 gastric), NGS of 639 genes and PD - L1 staining were done.ResultsIn colorectal cancer, PREX2 mutations were associated with increased TMB, MSI, TMB-H, and MSI-H. Mechanistically, this is related to an increased number of tumor pathway mutations, higher PD - L1 expression, increased immune infiltration, and immune - related pathway enrichment. Cetuximab and Bortezomib sensitivity was higher in PREX2 - mutated colorectal cancer. In gastric cancer, there are no established immune associations with PREX2 mutations.ConclusionPREX2 mutations may serve as a novel predictive biomarker for immunotherapy in CRC, potentially enhancing antitumor immunity via microenvironment modulation, but lack predictive value in GC. These findings highlight PREX2's role in refining patient stratification for immune checkpoint inhibitors.

BackgroundBreast cancer, the leading cause of cancer deaths among women, exhibits high heterogeneity, affecting prognosis. Understanding this heterogeneity and developing prognostic models are crucial for accurate identification of high-risk patients.MethodsAccessing breast cancer gene expression and clinical data from public datasets, we identified differential expression genes in tumor vs. non-tumor tissues using TCGA data. Key DEGs were then selected using LASSO and Cox regression, and a prognostic risk model (BRCA-DEGs-LASSO-Cox) was constructed. Survival analysis estimated model predictability, identifying high-risk patients. Correlation between risk score and signaling pathways, immune status, and drug sensitivity was analyzed. Molecular mechanisms underlying high-risk patients were discussed.ResultsOur analysis identified 1217 downregulated and 689 upregulated DEGs in breast cancer tumor tissues. A BRCA-DEGs-LASSO-Cox model was constructed using four key DEGs, stratifying patients into high/low-risk groups. High-risk patients had worse OS across cohorts and were associated with androgen, estrogen, and PI3 K signaling pathway dysregulation. They also exhibited immune status dysregulation and drug sensitivity disturbances. Molecular mechanism analysis indicated abnormal regulation of cell cycle, mitosis, and immune-related signals in high-risk patients, explaining their poorer prognosis.ConclusionsBRCA-DEGs-LASSO-Cox model effectively identifies high-risk breast cancer patients, revealing key signaling pathways, immune status, drug sensitivity, and molecular mechanisms.

To investigate the expression of serum high mobility group protein 1 (HMGB1), amyloid A (SAA), and tumor-specific growth factor (TSGF) in patients with colon cancer (CRC) and the value of prognostic assessment. Sixty cases of CRC patients admitted to our hospital from January 2018 to December 2020 were selected and set as the CRC group; 60 cases of inflammatory bowel disease (IBD) patients admitted during the same period were set as the IBD group, and 60 cases of those who were admitted to the hospital for health experience during the same period were set as the control group. The serum HMGB1, SAA, and TSGF levels of each group were detected to analyze their expression in CRC patients and their relationship with prognosis, compare the serum HMGB1, SAA, and TSGF levels of each group, and compare the serum HMGB1, SAA, and TSGF levels of patients with CRC with different clinical features. After 8 to 36 months of follow-up, CRC patients were grouped according to their prognosis (good prognosis group and poor prognosis group), and serum HMGB1, SAA, and TSGF levels were compared between the two groups. The predictive value of serum HMGB1, SAA, TSGF and their combined assays on the prognosis of CRC patients was analyzed using the subject's work characteristic curve (ROC). Serum HMGB1, SAA, and TSGF levels were significantly higher in the CRC group than in the IBD group (< 0.05), and serum HMGB1, SAA, and TSGF levels were significantly higher in the IBD group than in the control group (< 0.05). Serum HMGB1, SAA, and TSGF levels were significantly higher in the CRC group than in the patients with TNM staging III than in the patients with TNM staging I-II (< 0.05). Serum HMGB1, SAA, and TSGF levels were significantly higher in patients with low differentiation than in patients with middle and high differentiation (< 0.05), serum HMGB1, SAA, and TSGF levels were significantly higher in patients with low differentiation than in patients with intermediate and high differentiation (< 0.05), and serum HMGB1, SAA, and TSGF levels were significantly higher in those who developed lymph node metastasis than in patients with intermediate and high differentiation (< 0.05). Serum HMGB1, SAA, and TSGF levels in the poor prognosis group were significantly higher than those of patients in the good prognosis group (< 0.05). The ROC curves showed that the area under the curve (AUC) of serum HMGB1, SAA, and TSGF for predicting the prognosis of patients with CRC were 0.790, 0.774, 0.733, respectively, and that the combined assay predicted the prognosis of patients with CRC with an AUC of 0903, which was higher than that of the test alone (= 2.536, 2.420, 2.218, = 0.013, 0.020, 0.031). Serum HMGB1, SAA, and TSGF expression was significantly higher in colon cancer patients than in patients with inflammatory bowel disease and healthy populations, and was associated with TNM stage, degree of differentiation, and the presence of lymph node metastasis.

BackgroundMultiple myeloma (MM) is virtually always preceded by monoclonal gammopathy of undetermined significance (MGUS). Elevated serum markers are used to classify MGUS patients into clinical risk categories. Previous research has indicated that the absence of a normal plasma cell signature in MGUS is linked to early progression.ObjectiveTo confirm that the presence of a "polyclonal plasma cell (PolyPC) signature" serves as a robust negative predictor of MGUS progression.Methods374 MGUS patients were enrolled, including 334 patients with stable disease and 40 patients who progressed to MM within 10 years. An oligonucleotide microarray analysis was performed on mRNA extracted from CD138-selected bone marrow plasma cells to evaluate gene expression profiles. The PolyPC signature was developed and validated to assess its role in predicting disease progression. Statistical analyses included Cox proportional hazards models to evaluate progression risk and receiver operating characteristic (ROC) curve analysis to determine the sensitivity, specificity, and overall predictive performance of the PolyPC score.ResultsThrough this retrospective study, we developed PolyPC signature based on gene expression profiles of normal, uninvolved plasma cells to predict MGUS progression risk. ROC analysis demonstrated that this signature accurately predicted the risk of MGUS progression (C-statistic: 0.792). A PolyPC score ≤ 11.6 identified a subset of 89 patients with a 10-year progression probability of 31.5% (28/89), while the remaining 285 patients had a progression probability of only 4.2% (12/285) ( < 0.01). Sensitivity and specificity were 70% (28/40) and 81.7% (273/334). The external validation using the SWOG-S0120 dataset reinforces the robustness and clinical applicability of the PolyPC score in predicting MGUS progression to MM.ConclusionsThe strength of the PolyPC signature is a powerful negative predictor of MGUS progression. These findings support incorporating PolyPC into MGUS management to identify patients needing more frequent and intensive monitoring.

BackgroundMetastasis-associated in colon cancer-1 (MACC1) is a novel oncogene involved in the growth and metastasis of tumors, which is overexpression in various tumors. MACC1 could promote the growth, invasion, and metastasis of colorectal cancer (CRC) by activating the HGF/MET signaling pathway . It has been confirmed that MACC1 mainly promotes the Warburg effect in gastric cancer cells through the PI3 K/AKT signaling pathway.ObjectiveHere, we mainly investigated the association between MACC1 and the glycolysis process in CRC cells.MethodsThe expression of MACC1 in CRC and its relationship with the patient's survival were analyzed by TCGA database. We used different concentrations of glucose medium to culture HT-29 and HCT-116 with or without siMACC1. Cell Counting Kit-8 assay was used to detect cell proliferation. The content of lactic acid and glucose in cells was examined by enzyme-linked immunosorbent assay, and extracellular acidification rate was also determined with Seahorse XFe96 Extracellular Flux Analyzer. Western blot was used to detect the protein expressions related to glycolysis. Immunofluorescence was conducted to observe the expression and distribution of GLUT4.ResultsIn this study, we observed that MACC1 was highly expressed in CRC and negatively correlated with the survival of patients. The expression of glycolysis related enzymes was significantly increased under the stimulation of different concentrations of glucose in HT-29 and HCT-116 cells. However, MACC1 knockdown could significantly reduce high glucose-induced the expressions of glycolysis-related enzymes. Besides, MACC1 knockdown could decrease the content of glucose and lactate, and inhibit glycolytic function in HT-29 and HCT-116 cells. Moreover, the expression of GLUT4 was significantly decreased in the two cell lines treated by 4.5 g/L or 9.0 g/L glucose with MACC1 knockdown. Additionally, MACC1 knockdown could inhibit high glucose-induced membrane translocation of GLUT4.ConclusionsMACC1 knockdown can attenuate glucose metabolism by inhibiting the membrane translocation of GLUT4 in CRC cells.

BackgroundConsidering the significance of circRNA-miRNA network underlying cervical cancer (CC) development, this investigation was devised to explore whether and how 6-methyladinosinek (mA)-adjusted hsa_circ_0101308/miR-224 axis participated in altering chemo-resistance in CC.MethodsForty-nine pairs of CC tissues and para-cancerous normal tissues were gathered, and CC cell lines, comprising HeLa, HeLa/DDP, HeLa/ADM and HeLa/TAX cell lines, were pre-prepared. Expressions of circRNAs, miRNAs and mRNAs were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and mA-modification of hsa_circ_0101308 was verified based on methylated RNA immunoprecipitation sequencing (MeRIP-Seq) assay. Among CC cell lines, their chemo-resistance was evaluated through CCK8 assay, and their viability was assessed via MTT assay.ResultsHsa_circ_0101308 expression markedly dwindled, accompanied by notably elevated expression of miR-224, within CC tissues, when compared with para-cancerous normal tissues ( < 0.05). Hsa_circ_0101308 sponed miR-224 and suppressed its expression in HeLa cell line ( < 0.05), and either under-expressed mA-adjusted hsa_circ_0101308 or over-expressed miR-224 strengthened viability of HeLa, HeLa/DDP, HeLa/ADM and HeLa/TAX cell lines ( < 0.05). Additionally, miR-224 targeted CADM1 and down-regulated its mRNA level ( < 0.05), which influenced p-PI3K/PI3K or p-Akt/Akt ratio ( < 0.05).ConclusionThe network combined by mA-adjusted hsa_circ_0101308 and miR-224 interfered with chemo-resistance in CC via acting upon CADM1 and PI3K/AKT pathway, which was conducive to optimizing CC treatment.

BackgroundAt present, there are no universal markers of tumor stem cells known, including for B-lymphomas. Previously, we have shown that Epstein-Barr virus-induced B-cell lymphoma culture contains cells capable of internalizing TAMRA-labeled DNA. These cells form sphere-forming centers and are essential for the development of xenografts genetically identical to the initial culture.ObjectiveTo analyze the stem characteristics of cells that internalize DNA.MethodsSorting and RNA sequencing of two subpopulations (TAMRA + and TAMRA-) of Epstein-Barr virus-induced B-cell lymphoma culture and a series of quantitative real-time reverse transcription PCR were performed.ResultsTAMRA + cells were shown to have increased synthesis of mRNA of genes associated with the maintenance of a poorly differentiated state (), self-renewal () and epithelial-mesenchymal transition (). Transcriptomic analysis revealed that in TAMRA + cells, the synthesis of mitochondrial genes, as well as caspases and some apoptosis inhibitors, is reduced. TAMRA + cells possess clonogenic properties, increased level of synthesis of mRNA for key genes associated with self-renewal and poorly differentiated state maintenance.ConclusionsInternalization of the TAMRA-DNA probe is the marker of B-lymphoma cancer stem cells and can be used to detect tumor stem cells and develop new approaches to targeted treatment of B-lymphoma.