Etiology, cancer stem cells and potential diagnostic biomarkers for esophageal cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu K
PROVIDER: S-EPMC6597177 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Etiology, cancer stem cells and potential diagnostic biomarkers for esophageal cancer.
Liu Kuancan K Zhao Tingting T Wang Junkai J Chen Yunyun Y Zhang Rui R Lan Xiaopeng X Que Jianwen J
Cancer letters 20190521
Esophageal cancer (EC) has been a leading cause of cancer death worldwide in part due to late detection and lack of precision treatment. EC includes two major malignancies, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Recent studies reveal that ESCC and EAC have distinct cell of origin and contain cancer stem cells (also known as tumor initiating cells) expressing different cell surface markers. These biomarkers have potentially important values for both early d ...[more]
Similar Datasets
Project description:Tumor cell radioresistance is a major contributor to radiotherapy failure, highlighting the importance of identifying predictive biomarkers for radioresistance. In this work, we established a radioresistant H460 (RR-H460) cell line from parental radiosensitive H460 lung cancer cells by exposure to fractionated radiation. The radiation-resistant, anti-apoptotic phenotype of RR-H460 cell lines was confirmed by their enhanced clonogenic survival and increased expression of the radioresistance genes Hsp90 and Her-3. RR-H460 cells displayed characteristics of cancer stem-like cells (CSCs), including induction of the surface marker CD44 and stem cell markers Nanog, Oct4, and Sox2. RR-H460 cells also exhibited sphere formation and malignant behavior, further supporting a CSC phenotype. Using proteomic analyses, we identified 8 proteins that were up-regulated in RR-H460 CSC lines and therefore potentially involved in radioresistance and CSC-related biological processes. Notably, 4 of these-PAI-2, NOMO2, KLC4, and PLOD3-have not been previously linked to radioresistance. Depletion of these individual genes sensitized RR-H460 cells to radiotoxicity and additively enhancing radiation-induced apoptosis. Our findings suggest the possibility of integrating molecular targeted therapy with radiotherapy as a strategy for resolving the radioresistance of lung tumors.
| S-EPMC4847996 | biostudies-literature
Project description:BackgroundImmune infiltrates in the tumor microenvironment have established roles in tumor growth, invasion, and metastasis. However, the diagnostic and prognostic potential of immune cell signature in esophageal squamous cell carcinoma (ESCC) remains unclear.ResultsThe proportions of 22 subsets of immune cells from 331 samples including 205 ESCC and 126 normal esophageal mucosa retrieved from TCGA, GEO, and GTEx databases were deciphered by CIBERSORT. Nine overlapping subsets of immune cells were identified as important features for discrimination of ESCC from normal tissue in the training cohort by LASSO and Boruta algorithms. A diagnostic immune score (DIS) developed by XGBoost showed high specificities and sensitivities in the training cohort, the internal validation cohort, and the external validation cohort (AUC: 0.999, 0.813, and 0.966, respectively). Furthermore, the prognostic immune score (PIS) was developed based on naive B cells and plasma cells using Cox proportional hazards model. The PIS, an independent prognostic predictor, classified patients with ESCC into low- and high-risk subgroups in the internal validation cohort (P = 0.038) and the external validation cohort (P = 0.022). In addition, a nomogram model comprising age, N stage, TNM stage, and PIS was constructed and performed excellent (HR = 4.17, 95% CI: 2.22-7.69, P < 0.0001) in all ESCC patients, with a time-dependent 5-year AUC of 0.745 (95% CI: 0.644 to 0.845), compared with PIS or TNM stage as a prognostic model alone.ConclusionOur DIS, PIS, and nomogram models based on infiltrated immune features may aid diagnosis and survival prediction for patients with ESCC.
| S-EPMC9251101 | biostudies-literature
Project description:Background:The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC). However, the association between APC methylation and the initiation and progression of EC is poorly understood. Purpose and methods:The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett's esophagus (BE), and 782 controls. Results:Our results showed higher methylation of APC in EC (OR = 23.33, P < 0.001) and BE (OR = 9.34, P < 0.001) than in normal controls. Whereas APC methylation in EC was similar to that in BE (P = 0.052), it was not associated with tumor stage (P = 0.204). Additionally, APC methylation was not significantly associated with overall survival (OS) and relapse-free survival (RFS) in patients with EC. The performance of APC methylation for the detection of EC and BE achieved areas under the receiver operating characteristic curves of 0.94 and 0.88, respectively. Conclusion:Our results imply that APC methylation detection is a potential diagnostic biomarker for EC and BE.
| S-EPMC5798573 | biostudies-literature
Project description:Esophageal cancer (EC) is a fatal digestive disease with a poor prognosis and frequent lymphatic metastases. Nevertheless, reliable biomarkers for EC diagnosis are currently unavailable. Accordingly, we have performed a comparative proteomics analysis on cancer and paracancer tissue-derived exosomes from eight pairs of EC patients using label-free quantification proteomics profiling and have analyzed the differentially expressed proteins through bioinformatics. Furthermore, nano-flow cytometry (NanoFCM) was used to validate the candidate proteins from plasma-derived exosomes in 122 EC patients. Of the 803 differentially expressed proteins discovered in cancer and paracancer tissue-derived exosomes, 686 were up-regulated and 117 were down-regulated. Intercellular adhesion molecule-1 (CD54) was identified as an up-regulated candidate for further investigation, and its high expression in cancer tissues of EC patients was validated using immunohistochemistry, real-time quantitative PCR (RT-qPCR), and western blot analyses. In addition, plasma-derived exosome NanoFCM data from 122 EC patients concurred with our proteomic analysis. The receiver operating characteristic (ROC) analysis demonstrated that the AUC, sensitivity, and specificity values for CD54 were 0.702, 66.13%, and 71.31%, respectively, for EC diagnosis. Small interference (si)RNA was employed to silence the CD54 gene in EC cells. A series of assays, including cell counting kit-8, adhesion, wound healing, and Matrigel invasion, were performed to investigate EC viability, adhesive, migratory, and invasive abilities, respectively. The results showed that CD54 promoted EC proliferation, migration, and invasion. Collectively, tissue-derived exosomal proteomics strongly demonstrates that CD54 is a promising biomarker for EC diagnosis and a key molecule for EC development.
| S-EPMC10651172 | biostudies-literature
Project description:BackgroundIn Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu). Identification of novel biomarkers that are customized to the specific causative factors would lead to early diagnosis and clearer prognosis of the diseases. This study aimed to find genetic biomarkers in blood to distinguish and identify CKDu from CKD as well as healthy populations from CKDu endemic and non-endemic areas of Sri Lanka.MethodsThe expression patterns of a selected panel of 12 potential genetic biomarkers were analyzed in blood using RT-qPCR. Fold changes of gene expressions in early and late stages of CKD and CKDu patients, and an apparently healthy population of a CKDu endemic area, Girandurukotte (GH) were calculated relative to apparently healthy volunteers from a CKDu non-endemic area, Kandy (KH) of Sri Lanka, using the comparative CT method.ResultsSignificant differences were observed between KH and early stage CKDu for both the insulin-like growth factor binding protein 1 (IGFBP1; p = 0.012) and kidney injury molecule-1 (KIM1; p = 0.003) genes, and KH and late stage CKD and CKDu for the glutathione-S-transferase mu 1 (GSTM1; p < 0.05) gene. IGFBP1 and KIM1 genes showed significant difference between the early and late stage CKDu (p < 0.01). The glutamate cysteine ligase catalytic subunit (GCLC) gene had significantly different expression between KH and all the other study groups (p < 0.01). The GH group was significantly different from the KH group for the oxidative stress related genes, G6PD, GCLC and GSTM1 (p < 0.01), and also the KIM1 gene (p = 0.003). IGFBP1, insulin-like growth factor binding protein 3 (IGFBP3), fibronectin 1 (FN1) and KIM1 showed significant correlations with serum creatinine, and IGFBP1, KIM1 and kallikrein 1 (KLK1) with eGFR (p < 0.05).ConclusionA panel consisting of IGFBP1, KIM1, GCLC and GSTM1 genes could be used in combination for early screening of CKDu, whereas these genes in addition with FN1, IGFBP3 and KLK1 could be used to monitor progression of CKDu. The regulation of these genes has to be studied on larger populations to validate their efficiency for further clinical use.
| S-EPMC5244589 | biostudies-literature
Project description:Diagnostic and therapeutic biomarkers useful for esophageal squamous cell carcinoma (ESCC) have the ability to increase the long term survival of cancer patients. A metabolomics study, using plasma from four groups including ESCC patients before, during, and after chemoradiotherapy (CRT) and healthy controls, was originally carried out by LC-MS to determine global alterations in the metabolic profiles and find biomarkers potentially applicable to diagnosis and monitoring treatment effects. It is worth pointing out that a clear clustering and separation of metabolic data from the four groups was observed, which indicated that disease status and treatment intervention resulted in specific metabolic perturbations in the patients. A series of metabolites were found to be significantly altered in ESCC patients versus healthy controls and in pre- versus post-treatment patients based on multivariate statistical data analysis (MVDA). To further validate the reliability of these potential biomarkers, an independent validation was performed by using the selected reaction monitoring (SRM) based targeted approach. Finally, 18 most significantly altered plasma metabolites in ESCC patients, relative to healthy controls, were tentatively identified as lysophosphatidylcholines (lysoPCs), fatty acids, l-carnitine, acylcarnitines, organic acids, and a sterol metabolite. The classification performance of these metabolites were analyzed by receiver operating characteristic (ROC)(1) analysis and a biomarker panel was generated. Together, biological significance of these metabolites was discussed. Comparison between pre- and post-treatment patients generated 11 metabolites as potential therapeutic biomarkers that were tentatively identified as amino acids, acylcarnitines, and lysoPCs. Levels of three of these (octanoylcarnitine, lysoPC(16:1), and decanoylcarnitine) were closely correlated with treatment effect. Moreover, variation of these three potential biomarkers was investigated over the treatment course. The results suggest that these biomarkers may be useful in diagnosis, as well as in monitoring therapeutic responses and predicting outcomes of the ESCC.
| S-EPMC3650341 | biostudies-literature
Project description:Gastric cancer (GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stage disease. However, response to chemotherapy varies widely, with some patients presenting no or only minor response to treatment. Hence, chemotherapy resistance is a major clinical problem that impacts on outcome. Unfortunately, to date there are no reliable biomarkers available that predict response to chemotherapy before the start of the treatment, or that allow modification of chemotherapy resistance. MicroRNAs (miRNAs) could provide an answer to this problem. miRNAs are involved in the initiation and progression of a variety of cancer types, and there is evidence that miRNAs impact on resistance towards chemotherapeutic drugs as well. This current review aims to provide an overview about the potential clinical applicability of miRNAs as biomarkers for chemoresistance in GC. The authors focus in this context on the potential of miRNAs to predict sensitivity towards different chemotherapeutics, and on the potential of miRNAs to modulate sensitivity and resistance towards chemotherapy in GC.
| S-EPMC4194550 | biostudies-other
Project description:Background: Esophageal squamous cell carcinoma (ESCC) is one of the most fatal diseases worldwide. Because early diagnosis is difficult, ESCC is mostly diagnosed at an advanced stage, leading to a poor overall prognosis. The purpose of this study was to explore the differences between plasma metabolic profiles in ESCC patients and healthy controls and to establish a diagnostic model of ESCC. Methods: In this study, a cohort of 310 subjects, containing 140 ESCC patients and 170 healthy controls (HC), was recruited. Participants were randomly separated into a training set (80 ESCCs, 80 HCs) and a validation set (60 ESCCs, 90 HCs) and their plasma metabolomics profiles were analyzed by ultra-performance liquid chromatography-tandem quadruple time-of-flight mass spectrometry (UPLC-QTOF/MS) technique. Univariate statistical analysis and multivariate analysis (MVA) methods were used to identify differential metabolites. Finally, the dysregulated pathways associated with ESCC were further explored and the diagnostic performance of the biomarker panel was evaluated. Results: Metabolic analyses identified 34 significant metabolites involved in the metabolism of amino acids, phospholipids, fatty acids, purine, and choline. Farthermore, an effective diagnostic model for ESCC was constructed based on eight metabolites. This panel of biomarkers consisted of hypoxanthine, proline betaine, indoleacrylic acid, inosine, 9-decenoylcarnitine, tetracosahexaenoic acid, LPE (20:4), and LPC (20:5). The model was verified and evaluated in the validation set. The AUC value of the ROC curve was 0.991(95% CI: 0.981-1.000, CI, Confidence interval), with a sensitivity (SE) of 98.8% and a specificity (SP) of 94.9% for the training set and 0.965(95% CI: 0.936-0.993), with a SE of 88.3% and a SP of 88.9% for the validation set. Among them, three biomarkers, indoleacrylic acid, LPC (20:5), and LPE (20:4), exhibited a trend associated with the ESCC progression. Conclusions: Our study identified a novel plasma biomarker panel, which clearly distinguishes ESCC patients and provides insight into the mechanisms of ESCC. This finding may form the basis for the development of a minimally invasive method for ESCC detection.
| S-EPMC7171502 | biostudies-literature
Project description:Next Generation Sequencing (NGS) was carried out on subjects who visited an oriental medicine clinic due to recurrent sleep disturbance, and 40 individuals (17 male and 23 female) were set as the sleep diorder (SD) group based on their scores on the sleep distrurbance questionnaire of Pittsburgh sleep quality index (PSQI). The control group consisted of 40 healthy individuals (20 males and females each), as assessed by both subjective diagnosis and test for metabolic syndrome factors.Ten individuals (five males and females each) from the SD and the control group, respectively, were allocated for NGS analysis.
2021-07-07 | GSE165041 | GEO
Project description:To develop new diagnostic and therapeutic tools to specifically target pancreatic tumors, it is necessary to identify cell-surface proteins that may serve as potential tumor-specific targets. In this study we used an azido-labeled bioorthogonal chemical reporter to metabolically label N-linked glycoproteins on the surface of pancreatic cancer cell lines to identify potential targets that may be exploited for detection and/or treatment of pancreatic cancer. Labeled glycoproteins were tagged with biotin using click chemistry, purified by streptavidin-coupled magnetic beads, separated by gel electrophoresis, and identified by liquid chromatography-tandem mass spectrometry (MS). MS/MS analysis of peptides from 3 cell lines revealed 954 unique proteins enriched in the azido sugar samples relative to control sugar samples. A comparison of the proteins identified in each sample indicated 20% of these proteins were present in 2 cell lines (193 of 954) and 17 of the proteins were found in all 3 cell lines. Five of the 17 proteins identified in all 3 cell lines have not been previously reported to be expressed in pancreatic cancer; thus indicating that novel cell-surface proteins can be revealed through glycoprotein profiling. Western analysis of one of these glycoproteins, ecto-5'-nucleotidase (NT5E), revealed it is expressed in 8 out of 8 pancreatic cancer cell lines examined. Further, immunohistochemical analysis of human pancreatic tissues indicates NT5E is significantly overexpressed in pancreatic tumors compared to normal pancreas. Thus, we have demonstrated that metabolic labeling with bioorthogonal chemical reporters can be used to selectively enrich and identify novel cell-surface glycoproteins expressed in pancreatic ductal adenocarcinomas.
| S-EPMC4846140 | biostudies-literature