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Proteomic Profiling of Gastric Signet Ring Cell Carcinoma Tissues Reveals Characteristic Changes of the Complement Cascade Pathway.

ABSTRACT: Signet ring cell carcinoma (SRCC) is a histological subtype of gastric cancer with distinct features in multiple aspects compared with adenocarcinomas (ACs). The lack of a systematic molecular overview of this disease has led to slow progress in its clinical practice. In the present proteomics study, gastric tissues were collected from tumors and adjacent tissues, including 14 SRCCs and 34 ACs, and laser capture microdissection (LCM) was employed to eradicate the cellular heterogeneity of the tissues. The proteomes of tissues were profiled by data-independent acquisition (DIA) mass spectrometry (MS). Based on the over 6000 proteins quantified, univariate analysis and pathway enrichment revealed that some proteins and pathways demonstrated differences between SRCC and ACs. Importantly, the upregulation of a majority of complement-related proteins was notable for SRCC but not for ACs. A hypothesis, based on the proteomics evidence, was proposed that the complement cascade was evoked in the SRCC microenvironment upon infiltration, and the SRCC cells survived the complement cytotoxicity by secreting endogenous negative regulators. Moreover, an attempt was made to establish appropriate cell models for gastric SRCC through proteomic comparison of the 15 gastric cell lines and gastric tumors. The predictions of a supervised classifier suggested that none of these gastric cell lines qualified to mimic SRCC. This study discovered that the complement cascade is activated at a higher level in gastric SRCC than in ACs.

SUBMITTER: Fan Y

PROVIDER: S-EPMC8121970 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Protein profiling reveals the characteristic changes of complement cascade pathway in the tissues of gastric signet ring cell carcinoma

Project description:Signet ring cell carcinoma (SRCC) is a histological subtype of gastric cancer with distinct features in multiple aspects compared to adenocarcinomas (ACs). Lacking of systematically molecular overview to this disease made a slow progress in its clinical practice. In the present proteomics study, gastric tissues were collected from tumor and adjacency including 14 SRCCs and 34 ACs, and laser capture microdissection (LCM) was employed to eradicate cellular heterogeneity of the tissues. Proteome of tissues were profiled by data independent acquisition (DIA) mass spectrometry (MS). Based on the over 6 000 proteins quantified. Univariate analysis and pathway enrichment revealed that some proteins and pathways bared the differences between SRCC and ACs. Importantly, the up regulation for a majority of complement-related proteins were iconic for SRCC but not for AC. A hypothesis, based on the proteomics evidence, was proposed that the complement cascade was evoked in the SRCC microenvironment upon infiltration, while the SRCC cells survived the complement cytotoxicity by secreting endogenous negative regulators. Moreover, an attempt was made to seek appropriate cell models for gastric SRCC, through proteomic comparison of the 15 gastric cell lines and the gastric tumors. The prediction of supervised classifier suggested none of these gastric cell lines qualified in mimicking SRCC. This study discovered that complement cascade is activated at a higher level in gastric SRCC than AC.

2021-02-25 | PXD022405 | Pride

Protein profiling reveals the characteristic changes of complement cascade pathway in the tissues of gastric signet ring cell carcinoma

2021-02-25 | PXD022627 | Pride

Protein profiling reveals the characteristic changes of complement cascade pathway in the tissues of gastric signet ring cell carcinoma

2021-02-25 | PXD022952 | Pride

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

DNA Methylation Profiling and Transcriptomic Changes in Signet Ring Cell Colorectal Cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-07-21 | GSE79794 | 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.

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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

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

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

Project description: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.

| S-EPMC8623627 | biostudies-literature

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