Serum Levels of Cytokine-Induced Apoptosis Inhibitor 1 (CIAPIN1) as a Potential Prognostic Biomarker of Cholangiocarcinoma.
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ABSTRACT:
SUBMITTER: Truong SDA
PROVIDER: S-EPMC8227425 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cholangiocarcinoma (CCA), a malignancy of the biliary epithelium, can arise at any point in the biliary system. We previously reported that CIAPIN1 is detectable in the sera and that its overexpression was associated with poor prognosis and metastasis of CCA patients. In this study, we investigated further its expression in CCA tissues, biological functions, and related signaling pathways in CCA cells. First, we examined CIAPIN1 expression in CCA tissues of 39 CCA patients using immunohistochemistry (IHC). Then, CIAPIN1-related proteins expressed in CCA cells were identified using RNA interference (siRNA) and liquid chromatography-mass spectrometry (LC-MS/MS). To predict the functions and signaling pathways of CIAPIN1 in CCA cells, the identified proteins were analyzed using bioinformatics tools. Then, to validate the biological functions of CIAPIN1 in the CCA cell line, transwell migration/invasion assays were used. CIAPIN1 was overexpressed in CCA tissues compared with adjacent noncancerous tissues. Its overexpression was correlated with lymph node metastasis. Bioinformatic analyses predicted that CIAPIN1 is connected to the TGF-β/SMADs signaling pathway via nitric oxide synthase 1 (NOS1) and is involved in the metastasis of CCA cells. In fact, cell migration and invasion activities of the KKU-100 CCA cell line were significantly suppressed by CIAPIN1 gene silencing. Our results unravel its novel function and potential signaling pathway in metastasis of CCA cells. CIAPIN1 can be a poor prognostic factor and can be a promising target molecule for CCA chemotherapy.
| S-EPMC9267148 | biostudies-literature
Project description:Cholangiocarcinoma is a common malignancy with increasing incidence worldwide. Most patients are diagnosed at the advanced stage with poor survival rate. Laminin subunit γ2 (LAMC2) is a heparin binding-associated gene involved in tumorigenesis and has been implicated in the prognosis of various types of cancers. However, it is unclear whether expression of LAMC2 is associated with the clinical outcome of patients with cholangiocarcinoma. In the present study, the role and prognostic value of LAMC2 expression in patients with cholangiocarcinoma was investigated. Clinical information and pathological characteristics were analyzed and the association between LAMC2 expression and clinical characteristics, pathological findings and patient outcomes, including metastasis-free and disease-specific survival, were investigated. Data from 182 patients with cholangiocarcinoma were evaluated. High LAMC2 expression was associated with higher tumor stage (P<0.001), large duct type (P=0.024) and poor histological grade (P=0.002). Kaplan-Meier analysis showed high LAMC2 expression was associated with lower overall (P=0.003), disease-specific (P=0.0025), local recurrence-free (P<0.0001) and metastasis-free survival (P<0.0001). Moreover, multivariate analysis demonstrated that increased LAMC2 expression was a significant predictive risk factor for overall [hazard ratio (HR) 1.713; P=0.034], disease-specific (HR 2.011; P=0.039), local recurrence-free (HR 2.721; P<0.001) and metastasis-free survival (HR 3.117; P<0.001). Gene enrichment analysis using Gene Ontology showed that terms associated with LAMC2 upregulation were 'regulation of platelet-derived growth factor receptor-βsignaling pathway' and 'platelet-derived growth factor receptor-β signaling pathway'. The present study indicated that LAMC2 was upregulated in cholangiocarcinoma tumor tissue and had an inverse association with overall, disease-specific, local recurrence-free and metastasis-free survival in patients with cholangiocarcinoma. These results suggested that LAMC2 may serve as a potential biomarker for cholangiocarcinoma.
| S-EPMC10655064 | biostudies-literature
Project description:BackgroundCell proliferation and migration are the determinants of malignant tumor progression, and a better understanding of related genes will lead to the identification of new targets aimed at preventing the spread of cancer. Some studies have shown that KIAA1199 (CEMIP) is a transmembrane protein expressed in many types of noncancerous cells and cancer cells. However, the potential role of KIAA1199 in the progression of cholangiocarcinoma (CCA) remains unclear.ResultsAnalysis of cancer-related databases showed that KIAA1199 is overexpressed in CCA. ELISA, immunohistochemistry, Western blotting and qPCR indicated high expression levels of KIAA1199 in serum, CCA tissues and CCA cell lines. In the serum (n = 41) and large sample validation (n = 177) cohorts, higher KIAA1199 expression was associated with shorter overall survival and disease-free survival times. At the cellular level, KIAA1199 overexpression (OE) promoted CCA growth and metastasis. Subcutaneous tumor xenograft experiments showed that KIAA1199 enhances CCA cell proliferation. Additionally, the expression levels of components in the EMT-related TGF-β pathway changed significantly after KIAA1199 upregulation and silencing.ConclusionKIAA1199 is a promising new diagnostic molecule and therapeutic target in CCA. The serum KIAA1199 level can be used as a promising clinical tool for predicting the overall postoperative outcomes of patients with CCA.MethodsCCA-related KIAA1199 data were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. To assess the prognostic impact of KIAA1199, an enzyme-linked immunosorbent assay (ELISA) was used to measure the serum level of KIAA1199 in 41 patients who underwent surgical resection. Immunohistochemical staining, Western blotting and qPCR were used to verify and retrospectively review the expression levels of KIAA1199 in cancer tissue specimens from 177 CCA patients. The effect of KIAA1199 on CCA was evaluated by cell-based functional assays and subcutaneous tumor xenograft experiments. The expression levels of proteins associated with epithelial-mesenchymal transition (EMT) and activation of relevant signaling pathways were measured via Western blotting.
| S-EPMC7762501 | biostudies-literature
Project description:Diagnostic and/or prognostic biomarkers for cholangiocarcinoma (CCA) are still insufficient with poor prognosis of patients. To discover a new CCA biomarker, we constructed our secretome database of three CCA cell lines and one control cholangiocyte cell line using GeLC-MS/MS. We selected candidate proteins by five bioinformatics tools for secretome analysis. The inclusion criteria were as follows: having predicted signal peptide or being predicted as non-classically secreted protein; together with having no transmembrane helix and being previously detected in plasma and having the highest number of signal peptide cleavage sites. Eventually, apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) was selected for further analysis. To validate APEX1 as a bio-marker for CCA, serum APEX1 levels of 80, 39, and 40 samples collected from CCA, benign biliary diseases (BBD), and healthy control groups, respectively, were measured using dot blot analysis. The results showed that serum APEX1 level in CCA group was significantly higher than that in BBD or healthy control group. Among CCA patients, serum APEX1 level was significantly higher in patients having metastasis than in those without metastasis. The higher level of serum APEX1 was correlated with the shorter survival time of the patients. Serum APEX1 level might be a diagnostic and prognostic biomarker for CCA.
| S-EPMC6770206 | biostudies-literature
Project description:AbstractCholangiocarcinoma (CCA) is one of the most common malignant tumors. Although gene-targeted therapies have significantly improved the outcome of many cancers, the results are still not satisfactory for patients with CCA. Owing to the lack of an effective biomarker for guiding clinical treatment and monitoring prognosis in patients with CCA, the purpose of this study was to identify a new biomarker that could help predict the outcome of patients with CCA using bioinformatics tools.Gene expression data were collected from three publicly available datasets, comprising 263 patients with CCA and 22 healthy controls. Differentially expressed genes were obtained using the limma package (FDR < 0.05, |Log2FC|>1), and the respective protein-protein interaction revealed five relevant genes in the STRING dataset (TOP2A, BUB1, RRM2, TYMS, and KIF4A). The immunohistochemistry and PCR were used to analyze the difference in KIF4A expression in CCA.Kinesin Family Member 4A (KIF4A) was the only gene significantly associated with overall patient survival (P .035), with higher KIF4A expression being associated with poor survival rates. Moreover, KIF4A was significantly correlated with the infiltration of activated memory T cells (P = .0198) and activated mast cells (P = .008) in the tumor microenvironment. Increase in KIF4A expression affected the infiltration degree of the immune cells, which may be involved in the regulation of immune tolerance by CCA cells. The results indicated that the expression of KIF4A in CCA was higher than that in paracancerous tissues.Taken together, these findings suggest that KIF4A could be a potential new biomarker in CCA for predicting the response of patients to targeted immunotherapies.
| S-EPMC8154480 | biostudies-literature
Project description:ObjectiveTo investigate the expression of glycosphingolipids in serum and tissue from patients with cholangiocarcinoma compared with healthy controls.MethodsNanospray ionization-linear ion trap mass spectrometry (NSI-MSn) was used to demonstrate the comparative structural glycomics of glycosphingolipids in serum from patients with cholangiocarcinoma (n=15), compared with healthy controls (n = 15). GM2 expression in cholangiocarcinoma tissues (n = 60) was evaluated by immunohistochemistry.ResultsEleven glycosphingolipids were detected by NSI-MSn: CMH (ceramide monohexose), Lac-Cer (galactose (Gal)β1-4 glucose (Glc)β1-1'-ceramide), Gb3 (Galα1-4Galβ1-4Glcβ1-1'-ceramide), Gb4/Lc4 (N-acetylgalactosamine (GalNAc)β1-3Galα1-4Galβ1-4Glcβ1-1'-ceramide/Galβ1-4 N-acetylglucosamine (GlcNAc)β1-3Galβ1-4Glcβ1-1'-ceramide), GM3 (N-acetylneuraminic acid (NeuAc)2-3Galβ1-4Glcβ1-1'-ceramide), GM2 (GalNAcβ1-4[NeuAc2-3]Galβ1-4Glcβ1-1'-ceramide), GM1 (Galβ1-3GalNAcβ1-4[NeuAc2-3]Galβ1-4Glcβ1-1'-ceramide), hFA (hydroxylated fatty acid)-CMH, hFA-Lac-Cer, hFA-Gb3, and hFA-GM3. Lac-Cer was the most abundant structure among the lactosides and globosides (normal, 24.40% ± 0.11%; tumor, 24.61% ± 2.10%), while GM3 predominated among the gangliosides (normal, 29.14% ± 1.31%; tumor, 30.53% ± 4.04%). The two glycosphingolipids that significantly differed between healthy controls and patients with cholangiocarcinoma were Gb3 and GM2. High expression of GM2 was associated with vascular invasion in tissue from patients with cholangiocarcinoma.ConclusionsAltered expression of glycosphingolipids in tissue and serum from patients with cholangiocarcinoma may contribute to tumor growth and progression. The ganglioside GM2, which significantly increased in the serum of patients with cholangiocarcinoma, represents a promising target as a biomarker for cholangiocarcinoma.
| S-EPMC7375732 | biostudies-literature
Project description:Discovering novel biomarkers that easily accessed is a key step towards the personalized medicine approach for gastric cancer patients. Integrin-β6 (ITGB6) is a subtype of integrin that is exclusively expressed on the surface of epithelial cells and is up-regulated in various tumors. In the present study, a retrospective cohort with 135 gastric cancer patients and a prospective cohort with 34 gastric cancer patients were constructed, ITGB6 expression were detected in both the serum specimens and the tissue specimens. Detailed clinicopathological parameters as well as patients' survival were recorded. A nomogram including ITGB6 expression was also constructed and validated to predict the prognosis of gastric cancer patients. Results showed that serum ITGB6 expression was obviously increased and associated with tumor stage in gastric cancer patients, serum ITGB6 expression was relatively high in patients with liver metastasis. High ITGB6 expression indicated a poor prognosis, and nomogram including serum ITGB6 expression could predict the prognosis of gastric cancer patients effectively. Moreover, serum ITGB6 expression was associated with ITGB6 expression in tumor tissues. Furthermore, combined serum ITGB6 and CEA levels contributed to the risk stratification and prognostic prediction for gastric cancer patients. In addition, the serum expression of ITGB6 decreased significantly after radical surgery, and a new rise in serum ITGB6 expression indicated tumor recurrence or progression. The present study identified a novel serum biomarker for the risk stratification, prognostic prediction and surveillance of gastric cancer patients.
| S-EPMC8593195 | biostudies-literature
Project description:BackgroundLysosome-associated protein transmembrane-4 beta (LAPTM4B) is an integral membrane protein overexpressed in various cancers and may function as a prognostic tumor marker. The present study is aimed at understanding the clinical significance of serum LAPTM4B in breast cancer (BC).MethodsSerum LAPTM4B level was evaluated in 426 BC patients, 40 benign breast disease, and 80 healthy controls by ELISA. We used the receiver operator characteristic (ROC) curve to assess the diagnostic significance. 46 BC patients were recruited to monitor the dynamic change of serum LAPTM4B during adjuvant therapy (AT). In addition, sera from a subset of 330 patients undergoing AT, including anti-HER2 treatment, were collected to evaluate the association between LAPTM4B levels and AT efficacy. Descriptive and explorative statistical analyses were used to assess LAPTM4 B's potential as a diagnostic and prognostic marker in BC.ResultsSerum LAPTM4B level was significantly increased in BC patients than benign group and controls. It could well discriminate BC from healthy controls with diagnostic accuracy with an AUC of 0.912, a sensitivity of 85.9%, and a specificity of 83.8%. Compared with pre-AT, serum LAPTM4B concentration remarkably decreased after AT. In addition, patients in the invalid response group (PD + SD) showed higher LAPTM4B levels than the valid response group (PR + CR).ConclusionOur results proposed that serum LAPTM4B had a high diagnostic and prognostic impact as a circulating biomarker in BC.
| S-EPMC9729050 | biostudies-literature
Project description:BackgroundDiabetic kidney disease (DKD) has become a major cause of chronic kidney disease. However, early diagnosis of DKD is challenging. Trimethylamine oxide (TMAO) is an intestinal microbial metabolite which might be associated with diabetes complications. The aim of this study was to investigate the correlation between TMAO and DKD.MethodsA cross-sectional study was conducted. A total of 108 T2DM patients and 33 healthy subjects were enrolled in this study. Multiple logistic regression analyses and area under receiver operating characteristic curves (AUROC) were performed to evaluate the correlation between serum TMAO and DKD.ResultsSerum TMAO levels were significantly higher in DKD patients than healthy control group and the NDKD (T2DM without combined DKD) group (P < 0.05). TMAO levels were negatively correlated with eGFR and positively correlated with urea nitrogen, ACR and DKD (P < 0.05). Logistic regression analysis indicated that serum TMAO was one of the independent risk factors for DKD patients (P < 0.05). In the diagnostic model, the AUROC of TMAO for the diagnosis of DKD was 0.691.ConclusionElevated levels of serum TMAO levels were positively associated with the risk of DKD in T2DM patients, which might be a potential biomarker for DKD.
| S-EPMC10388659 | biostudies-literature
Project description:Sera of experimental autoimmune encephalomyelitis (EAE) or control mice were collected at day 18 post immunization. Comprehensive analysis of cytokine levels were performed by using commercially available RayBio Mouse Cytokine Array 2 (RayBiotech, Inc.) according to manufacturer’s protocol
2013-05-31 | GSE47499 | GEO