Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptomic Profiling Reveals AKR1C1 and AKR1C3 Mediate Cisplatin Resistance in Signet Ring Cell Gastric Carcinoma via Autophagic Cell Death.

ABSTRACT: Signet ring cell gastric carcinoma (SRCGC) is a lethal malignancy that has developed drug resistance to cisplatin therapies. The aim of this study was to characterize the acquisition of the cisplatin-resistance SRCGC cell line (KATO/DDP cells) and to understand the molecular mechanisms underlying cisplatin resistance. Transcriptomic and bioinformatic analyses were used to identify the candidate gene. This was confirmed by qPCR and Western blot. Aldoketoreductase1C1 and 1C3 (AKR1C1 and AKR1C3) were the most promising molecules in KATO/DDP cells. A specific inhibitor of AKR1C1 (5PBSA) and AKR1C3 (ASP9521) was used to enhance cisplatin-induced KATO/DPP cell death. Although cisplatin alone induced KATO/DDP apoptosis, a combination treatment of cisplatin and the AKR1C inhibitors had no influence on percent cell apoptosis. In conjunction with the autophagy inhibitor, 3MA, attenuated the effects of 5PBSA or ASP9521 to enhance cisplatin-induced cell death. These results indicated that AKR1C1 and 1C3 regulated cisplatin-induced KATO/DDP cell death via autophagy. Moreover, cisplatin in combination with AKR1C inhibitors and N-acetyl cysteine increased KATO/DDP cells' viability when compared with a combination treatment of cisplatin and the inhibitors. Taken together, our results suggested that AKR1C1 and 1C3 play a crucial role in cisplatin resistance of SRCGC by regulating redox-dependent autophagy.

SUBMITTER: Phoo NLL

PROVIDER: S-EPMC8623627 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Transcriptomic profilling of cisplatin sensitive and resistance in signet ring KATOIII gastric cancer cells

Project description:Purpose: The goal of our study is to identify the differentially expressed genes between cispaltin sensitive and cisplatin resistance gastric cancer cell line. Methods: Transcriptome sequencing of cisplatin sensitive and cisplatin resistance KATOIII cells were generated by Illumina HiSeq TM, for triplicates Results : Using an optimized data analyzed workflow, we mapped 57773 genes and were found 5966 differentially expressed genes between cisplatin sensitive KATOIII and cisplatin resistance KATO/DDP cell lines.

2021-10-22 | GSE186205 | GEO

Gastric Signet Ring Cell Carcinoma: Current Management and Future Challenges.

Project description:Recent advances in the epidemiology, pathology, molecular mechanisms, and combined modality therapy (CMT) fields have shown that gastric signet ring cell carcinoma (GSRC) should be considered a distinct cancerous entity. Clinical management of this cancer is challenging, with chemoradioresistance and poor outcomes in advanced stages. Pathological and molecular sets of GSRC demonstrate different features of poor cohesion and differentiation according to the WHO, Japanese Gastric Cancer Association, and Laurén classifications. These features also result in poor response to adjuvant and neoadjuvant chemoradiotherapy. Certain studies of GSRC showed the disputed effectiveness of hyperthermic intraperitoneal chemotherapy and immunotherapy. Our aim was to discuss how an improved understanding of these therapeutic benefits may provide better treatment selection for patients, and therefore improve survival. The challenges in the new understanding of GSRC in routine practice and pathology, and the current limitations of treatment will also be discussed.

| S-EPMC7478370 | biostudies-literature

Diagnostic value of dual-source, dual-energy computed tomography combined with the neutrophil-lymphocyte ratio for discriminating gastric signet ring cell from mixed signet ring cell and non-signet ring cell carcinomas.

Project description:PurposeTo explore the diagnostic value of dual-source computed tomography (DSCT) and neutrophil to lymphocyte ratio (NLR) for differentiating gastric signet ring cell carcinoma (SRC) from mixed SRC (mSRC) and non-SRC (nSRC).MethodsThis retrospective study included patients with gastric adenocarcinoma who underwent DSCT between August 2019 and June 2021 at our Hospital. The iodine concentration in the venous phase (ICvp), standardized iodine concentration (NICVP), and the slope of the energy spectrum curve (kVP) were extracted from DSCT data. NLR was determined from laboratory results. DSCT (including ICVP, NICVP, and kVP) and combination (including DSCT model and NLR) models were established based on the multinomial logistic regression analysis. The receiver operator characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic value.ResultsA total of 155 patients (SRC [n = 45, aged 61.22 ± 11.4 years], mSRC [n = 60, aged 61.09 ± 12.7 years], and nSRC [n = 50, aged 67.66 ± 8.76 years]) were included. There were significant differences in NLR, ICVP, NICVP, and kVP among the SRC, mSRC, and nSRC groups (all P < 0.001). The AUC of the combination model for SRC vs. mSRC + nSRC was 0.964 (95% CI: 0.923-1.000), with a sensitivity of 98.3% and a specificity of 86.7%, higher than with DSCT (AUC: 0.959, 95% CI: 0.919-0.998, sensitivity: 90.0%, specificity: 89.9%) or NLR (AUC: 0.670, 95% CI: 0.577-0.768, sensitivity: 62.2%, specificity: 61.8%).ConclusionDSCT combined with NLR showed high diagnostic efficacy in differentiating SRC from mSRC and nSRC.

| S-EPMC11335798 | biostudies-literature

Transcriptomic changes in signet ring cell colorectal cancer

Project description:Data used to look for gene expression changes correlating with DNA methylation in signet ring cell colorectal cancer.

2017-07-21 | GSE79793 | GEO

A Prognostic Model for Patients With Gastric Signet Ring Cell Carcinoma.

Project description:BackgroundThe aim of our study was to develop a nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRC).MethodsGSRC patients from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and validation sets. Multivariate Cox regression analyses screened for OS and CSS independent risk factors and nomograms were constructed.ResultsA total of 7,149 eligible GSRC patients were identified, including 4,766 in the training set and 2,383 in the validation set. Multivariate Cox regression analysis showed that gender, marital status, race, AJCC stage, TNM stage, surgery and chemotherapy were independent risk factors for both OS and CSS. Based on the results of the multivariate Cox regression analysis, prognostic nomograms were constructed for OS and CSS. In the training set, the C-index was 0.754 (95% CI = 0.746-0.762) for the OS nomogram and 0.762 (95% CI: 0.753-0.771) for the CSS nomogram. In the internal validation, the C-index for the OS nomogram was 0.758 (95% CI: 0.746-0.770), while the C-index for the CSS nomogram was 0.762 (95% CI: 0.749-0.775). Compared with TNM stage and SEER stage, the nomogram had better predictive ability. In addition, the calibration curves also showed good consistency between the predicted and actual 3-year and 5-year OS and CSS.ConclusionThe nomogram can effectively predict OS and CSS in patients with GSRC, which may help clinicians to personalize prognostic assessments and clinical decisions.

| S-EPMC8258759 | biostudies-literature

Prognostic Nomograms for Nonelderly Adults with Gastric Signet Ring Cell Carcinoma.

Project description:BackgroundNomograms were established to predict the survival for gastric signet ring cell carcinoma (GSRC) in young and middle-aged adults. Material and Methods. Eligible patients with GSRC from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and then divided into a training and a testing cohort in proportion. Independent prognostic factors were picked by univariate and multivariate Cox regression analysis to set up nomograms. The predictive effect and clinical value of nomograms were evaluated by the concordance index (C-index), calibration curves, and receiver operating characteristic curve (ROC).ResultsA total of 1686 GSRC patients were subsumed into this case for analysis, including a training (n = 1180) and a testing cohort (n = 506). Independent risk factors related to overall survival (OS) and cancer-specific survival (CSS) comprised of race, TNM stage, tumor size, number of positive lymph nodes (PLNE), and chemotherapy. For OS, the C-indexes of the training and testing cohorts were 0.737 and 0.752, while for CSS, C-indexes were, respectively, 0.749 and 0.751. These revealed that nomograms accurately predicted OS and CSS. Calibration curves and ROC demonstrated the apparent superiority of nomograms.ConclusionWe built a well-understood and comprehensive prognostic assessment model for GSRC, which provided an individualized survival prediction in the form of a quantitative score that can be considered for clinical practice.

| S-EPMC8016563 | biostudies-literature

Establishment of gastric signet ring cell carcinoma organoid for the therapeutic drug testing.

Project description:Signet ring cell carcinoma (SRCC) has specific oncogenesis and phenotypic and treatment resistance heterogeneity. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. Tumor organoids have recently emerged as an ideal model for drug testing and screening. Here, we report gastric organoids established from tumor tissues comprising four SRCCs and eight non-SRCCs. Tumor organoids demonstrated different growth characteristics and morphologies. Changes in the original tumor genome were maintained during long-term culture from whole-exome sequencing (WES) analysis. Immunohistochemistry and H&E staining showed that the tissue characteristics of the primary tumor could be recapitulated. In addition, organoid lines successfully formed tumors in immunodeficient mice and maintained tumorigenic character. Different responses to 5-fluorouracil, oxaliplatin, docetaxel and irinotecan treatment were observed in SRCC and non-SRCC organoids. These results demonstrate that gastric organoid drug models, including SRCC, were highly similar to the original tumors in phenotypic and genotypic profiling and could be as living biomarkers for drug response testing.

| S-EPMC8748936 | biostudies-literature

Prognostic Impact of the Signet Ring Cell Type in Node-Negative Gastric Cancer.

Project description:Little is known regarding the prognostic impact of the signet ring cell (SRC) histotype on negative lymph nodes (LNs) in gastric cancer (GC). In this study, we aimed to investigate the differences between SRC and non-SRC GC patients without LN metastasis. The medical records of patients with GC who underwent gastrectomy at Sun Yat-Sen University Cancer Centre from 1996 to 2012 were reviewed to analyse the clinicopathologic characteristics associated with survival. A total of 480 cases of GC patients without LN metastasis were identified, which included 90 SRC GC patients and 390 non-SRC GC patients. Between the two groups, there were a host of significant differences in the American Joint Committee on Cancer, 7th edition (AJCC) stage. We found that SRC histology was correlated with a poor prognosis in terms of recurrence in node-negative GC patients and that SRC histologic analysis combined with AJCC staging maybe an effectual method for prediction of the recurrence rate. Additionally, we found that SRC GC presents a more dismal overall prognosis in patients with perineural or vascular invasion.

| S-EPMC4933873 | biostudies-other

Postoperative Radiotherapy Improves Survival in Gastric Signet-Ring Cell Carcinoma: a SEER Database Analysis.

Project description:Purpose:To identify the potential therapeutic role of postoperative radiotherapy (RT) in patients with locally advanced (stage II and stage III) gastric signet ring cell carcinoma (SRC). Materials and methods:Patients with locally advanced gastric SRC from the Surveillance, Epidemiology, and End Results program database between 2004 and 2012 were included in our study. Univariate and multivariate Cox proportional models were performed, and survival curves were generated to evaluate the prognostic effect of postoperative RT and surgery alone on SRC patients. Propensity score matching (PSM) was used to avoid selection bias among the study cohorts. Results:We found that patients with postoperative RT had better probability of survival compared with those who did not receive RT (overall survival [OS], P<0.001; cancer-specific survival [CSS], P<0.001). After PSM, analysis of both overall and CSS showed that patients who underwent postoperative RT had better prognosis than those receiving surgery alone in the matched cohort (OS, P=0.00079; CSS, P=0.0036). Multivariate Cox proportional model indicated that postoperative RT had better effect on prognosis compared with surgery alone with respect to both overall (hazard ratio [HR], 0.716; 95% confidence interval [95% CI], 0.590-0.87; P=0.001) and CSS (HR, 0.713; 95% CI, 0.570-0.890; P=0.003). Conclusions:Postoperative RT had better prognosis compared with surgery alone for both overall and CSS for patients with locally advanced gastric SRC.

| S-EPMC6928086 | biostudies-literature

Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer.

Project description:Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however, with no systematical investigation for prognostic genomic features. Here we report a systematic investigation conducted in 1868 Chinese gastric cancer patients indicating that signet-ring cells content was related to multiple clinical characteristics and treatment outcomes. We thus perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation, prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet-ring cell content, age at diagnosis, female/male ratio, and TNM stage. Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes, and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26 introduced cell lines. Overall, this study provides insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.

| S-EPMC6026495 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data