Signet Ring Cell Carcinoma Patients Research Articles

Individualized prediction of conditional survival for colorectal signet-ring cell carcinoma patients.

Conditional survival (CS) considers the time already survived after surgery and may provide additional survival information. The authors sought to construct and validate novel conditional survival nomograms for the prediction of conditional overall survival (OS) and cancer-specific survival (CSS) of colorectal signet-ring cell carcinoma (SRCC) patients. Patients diagnosed with stage I-III SRCC between 2010 and 2019 were identified from the Surveillance, Epidemiology, and End Results database. The formula calculating CS was: CS(x|y) = S(x+y)/S(x), where S(x) represents the survival at x years. CS nomograms were then constructed to predict the 5-year conditional OS and CSS, followed by internal validation. A total of 944 colorectal SRCC patients were finally identified in this study. The 5-year OS and CSS improved gradually with additional survival time. Univariate and multivariate Cox regression analysis conducted in training set revealed that age, race, T stage, LNR, and perineural invasion were independent risk factors for both OS and CSS. Two nomograms with considerable predictive ability were successfully constructed [area under the curve (AUC) for OS: 0.788; AUC for CSS: 0.847] and validated (AUC for OS: 0.773; AUC for CSS: 0.799) for the prediction of 5-year OS and CSS, based on the duration of 1-4 years post-surgery survival. The probability of achieving 5-year OS and 5-year CSS in colorectal SRCC patients improved gradually with additional time. Conditional nomograms considering survival time will be more reliable and informative for risk stratification and postoperative follow-up.

Prognostic and predictive value of tumor deposits in advanced signet ring cell colorectal cancer: SEER database analysis and multicenter validation.

Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P < 0.05). Compared to the TD-negative group, the TD-positive group showed significantly poorer CSS (the training cohort: HR, 1.87; 95% CI, 1.52-2.31; the validation cohort: HR, 2.43; 95% CI, 1.55-3.81; all P values < 0.001). This association was significant in stage III but not in stage IV. In the multivariate model, after adjusting for covariates, TD maintained an independent prognostic value (P < 0.05). A nomogram model including TD, N stage, T stage, TNM stage, CEA, and chemotherapy was constructed. Through internal and external validation, the model demonstrated good calibration and accuracy. Further survival curve analysis based on individual scores from the model showed good discrimination. TD positivity is an independent factor of poor prognosis in colorectal SRCC patients, and it is more effective to predict the prognosis of colorectal SRCC by building a model with TD and other clinically related variables.

A novel log odds of positive lymph nodes–based nomogram for predicting overall survival in patients with colorectal signet ring cell carcinoma: a SEER population-based study

PurposeConsidering the poor prognosis and high lymph node (LN) involvement rate of colorectal signet ring cell carcinoma (SRCC), this study aimed to construct a prognostic nomogram to predict overall survival (OS) with satisfactory accuracy and utility, based on LN status indicators with superior predictability.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, we obtained cases of colorectal SRCC patients and employed univariate and multivariate Cox analyses to determine independent prognostic factors. Kaplan–Meier curves were utilized to visualize survival differences among these factors. Receiver operating characteristic curves were generated to assess predictive performances of models incorporating various LN status indicators. A novel nomogram, containing optimal LN status indicators and other prognostic factors, was developed to predict OS, whose discriminatory ability and accuracy were evaluated using calibration curves and decision curve analysis.ResultsA total of 1663 SRCC patients were screened from SEER database. Older patients and those with grades III–IV, tumor sizes > 39 mm, T3/T4 stage, N1/N2 stage, M1 stage, and higher log odds of positive lymph nodes (LODDS) values exhibited poorer prognoses. Age, grade, tumor size, TNM stage, and LODDS were independent prognostic factors. The model containing N stage and LODDS outperformed the one relying solely on N stage as LN status indicator, resulting in a validated nomogram for accurately predicting OS in SRCC patients.ConclusionThe integration of LODDS, N stage, and other risk factors into a nomogram offered precise OS predictions, enhancing therapeutic decision-making and tailored follow-up management for colorectal SRCC patients.

Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma.

The Alcian blue (AB) and periodic acid Schiff (PAS) stains are representative mucus markers in gastric signet ring cell carcinoma (SRCC). They are low-cost special staining methods used to detect acidic mucus and neutral mucus, respectively. However, the clinical importance of the special combined AB and PAS stain is unclear. To investigate AB expression, PAS expression and the AB-to-PAS (A/P) ratio in gastric SRCC patients and to assess patient prognosis. Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS, and signet ring cell positivity was assessed quantitatively. Immunohistochemical staining for Ki67, protein 53 (P53) and human epidermal growth factor receptor 2 (HER2) was performed simultaneously. The cancer-specific survival (CSS) rate was estimated via Kaplan-Meier analysis. Cox proportional hazards models were used for univariate and multivariate survival analyses. Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup (P < 0.001). The 3-year CSS rate in the A/P ≤ 0.5 group was significantly greater than that in the A/P > 0.5 group (P = 0.042). Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter, lymph node metastasis, vessel carcinoma embolus, tumor stage, the A/P ratio and the expression of Ki67, P53 and the PAS. Cox multivariate regression analysis confirmed that low PAS expression [hazard ratio (HR) = 3.809, 95% confidence interval (CI): 1.563-9.283, P = 0.003] and large tumor diameter (HR = 2.761, 95%CI: 1.086-7.020, P = 0.033) were independent risk factors for poor prognosis. A/P > 0.5 is potentially a risk factor for prognosis, and low PAS expression is an independent risk factor in the prognosis of gastric SRCC. PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

A nomogram for the prediction of survival for colorectal signet ring cell carcinoma after surgery: A population-based study.

The aim was to construct and verify a nomogram-based assessment of cancer-specific survival (CSS) in patients with colorectal signet ring cell carcinoma after surgery. Patients were collected from Surveillance, Epidemiology, and End Results program between 2004 and 2015. Independent prognostic indicators were determined in the training cohort by Cox regression model. We identified 2217 eligible patients, who were further categorized into the training set (n = 1693) as well as the validation set (n = 524). Multivariate analysis revealed that age at diagnosis, gender, grade, tumor size, T stage, N stage, and M stage were independent predictive indicators. Then, the above 7 predictive factors were incorporated into a nomogram model to assess CSS, which showed good calibration and discrimination capacities in both sets. Both internal and external calibration plot diagrams revealed that the actual results were consistent with the predicted outcomes. The time-independent area under the curves for 3-year and 5-year CSS in the nomogram were larger than American Joint Committee on Cancer and Surveillance, Epidemiology, and End Results summary stage system. Moreover, decision curve analysis indicated the clinical utility of the nomogram. The nomogram demonstrated favorable predictive accuracy of survival in colorectal signet ring cell carcinoma patients after surgery, which should be further confirmed before clinical implementation.

The prognostic ability of radiotherapy of different colorectal cancer histological subtypes and tumor sites

The prognostic significance of radiotherapy (RT) for colorectal cancer (CRC) has shown conflicting results, particularly among different pathological subtypes, including adenocarcinoma (AC), mucinous adenocarcinoma (MC), and signet-ring cell carcinoma (SR). This study analyzed the prognosis of three pathological CRC types and focused on the prognostic significance of RT on three CRC histological subtypes. Patients diagnosed with AC (n = 54,174), MC (n = 3813), and SR (n = 664) in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database (2010–2017) were evaluated. Cox regression models and competitive risk models were built to assess the effect of RT on the risk of CRC-associated death. Potential interactions between RT and stratified variables including age, sex, and tumor location were examined by multiplicative models. Compared with AC patients, SR patients had the worst overall survival (OS) among 3 subtypes of CRC (log-rank test, p < 0.001). Compared with patients who did not receive radiotherapy, RT was associated with a 1.09-fold (HR = 1.09, 95%[CI]: 1.03, 1.15) elevated risk of death among AC patients. In the SR group, RT significantly reduced the risk of death by 39% (HR = 0.61, 95%[CI]: 0.39–0.95). However, RT did not appear to independently influence survival in the MC group (HR = 0.96, 95%[CI]: 0.77, 1.21). In the subgroup analysis, tumor location (colon and rectum) significantly modified the association between RT and the risk of death among the AC and SR patients (p for interaction < 0.05). SR patients exhibited a worse OS (overall survival) than AC patients, and the effect of RT varied according to CRC histological subtypes. This can ultimately lead to more personalized and effective treatment strategies for CRC patients.

Prognostic Performance of Three Lymph-Node Staging Systems on Gastric Signet-Ring-Cell Carcinoma.

The lymph-node staging system can predict the prognosis of gastric signet-ring-cell carcinoma (SRCC). However, there are significant differences in lymph-node status between early SRCC and advanced SRCC. Additionally, the optimal system for early and advanced SRCC remains unknown. This study retrospectively analyzed 693 SRCC patients who underwent radical resection in the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital. The predicted performance of three lymph-node staging systems, including pN staging, lymph-node metastasis rate (LNR), and log odds of positive lymph nodes (LODDS), was compared using the receiver characteristic operating curve (ROC) and c-index. The Kaplan-Meier method and the log-rank test analyzed the overall survival of patients. The Cox risk regression model identified independent risk factors associated with patient outcomes. The nomogram was made by R studio. The 693 SRCC included 165 early SRCC and 528 advanced SRCC. ROC showed that LODDS had better predictive performance than pN and LNR in predicting prognosis regardless of early or advanced SRCC. LODDS can be used to predict the prognosis of early and advanced SRCC and was an independent risk factor associated with patient outcomes (p = 0.002, p < 0.001). Furthermore, the nomogram constructed by LODDS and clinicopathological features had good predictive performance. LODDS showed clear prognostic superiority over both pN and LNR in early and advanced SRCC.

Clinicopathologic and prognostic factors of patients with T3/T4 colorectal signet ring cell carcinoma: a population-based study

BackgroundTo evaluate cancer-specific survival (CSS) and construct a nomogram to predict the CSS of patients with colorectal signet ring cell carcinoma (SRCC).MethodsThe data for patients with colorectal SRCC from 2000 to 2019 was identified from Surveillance, Epidemiology, and End Results (SEER) database. Propensity Score Matching (PSM) was used to minimize bias between SRCC and adenocarcinoma patients. Kaplan–Meier method and log-rank test were used to estimate the CSS. A nomogram was constructed based on the independent prognostic factors identified by univariate and multivariate Cox proportional hazards regression analyses. The model was evaluated by receiver operating characteristic (ROC) curves and calibration plots.ResultsPoor CSS was more common in patients with colorectal SRCC, especially in patients with T4/N2 stage, tumor size > 80 mm, grade III-IV, and chemotherapy. Age, T/N stage, and tumor size > 80 mm were identified as independent prognostic indicators. And a prognostic nomogram was constructed and validated as an accurate model for the CSS of patients with colorectal SRCC by ROC curves and calibration plots.ConclusionPatients with colorectal SRCC have a poor prognosis. And the nomogram was expected to be effective in predicting the survival of patients with colorectal SRCC.

The prognostic value of FAR and a novel FAR-CA125 score in resectable gastric signet ring cell carcinoma patients.

The fibrinogen to albumin ratio (FAR) is increasingly regarded as a potential biomarker for predicting prognosis in variety of malignant tumors, but not in gastric signet ring cell carcinoma (GSRC). This study seeks to examine the prognostic value of the FAR and explore a novel FAR-CA125 score (FCS) in resectable GSRC patients. A retrospective cohort was conducted including 330 GSRC patients who underwent curative resection. Kaplan-Meier (K-M) and Cox regression were used to analysis the prognostic value of FAR and FCS. And a predictive nomogram model was developed. The optimal cut-off values for CA125 and FAR were 9.88 and 0.0697, respectively, according to the receiver operating characteristic curve (ROC). Th area under the ROC curve of FCS is higher than CA125 and FAR. 330 patients were grouped into three groups according to the FCS. High FCS was related to males, anemia, tumor size, TNM stage, lymph node metastasis, tumor invasion depth, SII, and pathological subtypes. K-M analysis showed that high FCS and FAR were associated with poor survival. In the multivariate analysis, FCS, TNM stage, and SII were independent prognostic factors for poor OS in resectable GSRC patients. And the predictive accuracy of clinical nomogram contained FCS was better than TNM stage. This study indicated that the FCS is a prognostic, and effective biomarker for patients with surgically resectable GSRC. Such developed FCS-based nomogram could be effective tools to assist the clinicians to determine the treatment strategy.

A model for predicting overall survival in bladder cancer patients with signet ring cell carcinoma: a population-based study

IntroductionThis study is to examine the predictors of survival and to construct a nomogram for predicting the overall survival (OS) of primary bladder signet ring cell carcinoma (SRCC) patients based on the analysis of the Surveillance, Epidemiology, and End Results (SEER) database.MethodsA total of 219 eligible patients diagnosed with SRCC were analyzed using the 2004–2015 data from SEER database. Univariate and multivariate Cox regression were used to determine independent prognostic factors, followed by development of a nomogram based on the multivariate Cox regression models. The consistency index (C-index), receiver operating characteristic (ROC) curve, and calibration curve were used to validate the prognostic nomogram.ResultsThe nomograms indicated appreciable accuracy in predicting the OS, with C-index of 0.771 and 0.715, respectively. The area under the curve (AUC) of the nomogram was 0.713 for 1 year, 0.742 for 3 years, and 0.776 for 5 years in the training set, while was 0.730 for 1 year, 0.727 for 3 years, and 0.697 for 5 years in the validation set. The calibration curves revealed satisfactory consistency between the prediction of deviation correction and ideal reference line.ConclusionsThe prognostic nomogram developed in the analytical data of SEER it provided high accuracy and reliability in predicting the survival outcomes of primary bladder SRCC patients and could be used to comprehensively assess the risk of SRCC. Moreover, they could enable clinicians to make more precise treatment decisions for primary bladder SRCC patients.

Prognostic value of log odds of positive lymph nodes, lymph node ratio, and N stage in patients with colorectal signet ring cell carcinoma: A retrospective cohort study.

Little attention has been paid in the prognosis of colorectal signet ring cell carcinoma (SRCC). This study aims to explore the predictive capacity of log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and pN stage in the prognosis of patients with colorectal SRCC. A retrospective cohort study was designed, and data were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Data on demographic characteristics, clinicopathological features, and treatment were extracted. Outcomes were overall survival (OS) and cancer-specific survival (CSS). Association of LODDS, LNR, and pN stage with OS and CSS were explored using Cox proportional hazard model and Cox competing risk model, respectively, with results showing as hazard ratio and 95% confidence interval (CI). Predictive performance of LODDS, LNR, and pN stage in OS and CSS was assessed by calculating C-index. A total of 2,198 patients were included in this study. LODDS, LNR, and pN stage were associated with the OS and CSS of colorectal SRCC patients (all P < 0.05). LODDS showed a good performance in the OS (C-index: 0.704, 95% CI: 0.690-0.718), which was superior to LNR (C-index: 0.657, 95% CI: 0.643-0.671) and pN stage (C-index: 0.643, 95% CI: 0.629-0.657). The C-index of LODDS, LNR, and pN stage for CSS was 0.733 (95% CI: 0.719-0.747), 0.713 (95% CI: 0.697-0.729), and 0.667 (95% CI: 0.651-0.683), respectively. LODDS displayed a better predictive capacity in the OS and CSS than LNR and pN stage, indicating that LODDS may be effective to predict the prognosis of colorectal SRCC in the clinic.

The therapeutic efficacy of radical prostatectomy and external beam radiation therapy in patients with different pathological patterns of prostate cancer

BackgroundWe aim to investigate the prognostic value of different pathological patterns of non-adenocarcinoma prostate cancers (PCa) in radical prostatectomy (RP) and external beam radiation therapy (EBRT). MethodsData of 470,258 localized PCa patients between 2004 and 2016 were collected from the Surveillance, Epidemiology, and End Results database. Propensity score matching was performed to balance the baseline characteristics of patients in different groups. Kaplan–Meier curves and Cox regression were used for survival analysis. Overall survival (OS) and cancer-specific survival (CSS) were set as endpoints. ResultsTotally, 1044 patients with non-adenocarcinoma patterns of PCa were included. Patients with small cell neuroendocrine carcinoma (SCNC) and neuroendocrine differentiation (NED) harbored the worst prognosis in both RP and EBRT among all pathological groups. RP exhibited superior effects to EBRT for this group of cases. Ductal carcinoma (DA) was also related to poorer survival outcomes versus PAC in both local therapies. Yet, for men with DA, both RP and EBRT still improved patients' prognosis against no local therapy (NLT), with RP being the superior modality. Cases harboring mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SRCC) shared comparable clinical outcomes to men with PAC. However, for cases with MA, neither RP nor EBRT was related to better survival outcomes against NLT, while for patients with SRCC, both RP and EBRT prolonged patients’ survival with similar effects. ConclusionsOur study provided a comprehensive view of the treatment effect of RP and EBRT in non-adenocarcinoma PCa patients. These findings could facilitate clinicians in making therapeutic decision-making for non-adenocarcinoma patients.

Clinicopathological characteristics and prognosis of gastric signet ring cell carcinoma.

BACKGROUNDThe clinicopathological features and prognosis of gastric signet ring cell carcinoma (GSRC) remain controversial, particularly with regard to sensitivity to postoperative adjuvant therapy.AIMTo compare the pathological features of GSRC with those of gastric adenocarcinoma of different degrees of differentiation and the differences in survival prognosis between the different disease processes.METHODSBy screening gastric cancer patients from 2010 to 2015 in the database of Surveillance, Epidemiology and End Results, and collecting the clinicopathological and prognostic data of gastric cancer patients who underwent surgery from January 2014 to December 2016 in the Second Affiliated Hospital of Nanchang University, we analyzed the general pathological characteristics of GSRC by the chi-square test. Univariate and multivariate analyses were conducted to compare the factors affecting the survival and prognosis of early and advanced gastric adenocarcinoma. The Kaplan-Meier curves were plotted to reveal the survival difference between early and advanced GSRC and different differentiated types of gastric adenocarcinoma. The prognosis model of advanced GSRC was established with R software, and the area under curve (AUC) and C-index were used to assess the accuracy of the model.RESULTSAnalysis of pathological features revealed that signet ring-cell carcinoma (SRC) was more frequently seen in younger (< 60 years), female, and White patients compared to non-SRC patients. SRC was less commonly associated with early gastric cancer (EGC) (23.60% vs 39.10%), lower N0 (38.61% vs 61.03%), and larger tumour sizes > 5 cm (31.15% vs 27.10%) compared to the differentiated type, while the opposite was true compared to the undifferentiated type. Survival prognostic analysis found no significant difference in the prognosis of SRC patients among EGC patients. In contrast, among advanced gastric cancer (AGC) patients, the prognosis of SRC patients was correlated with age, race, tumour size, AJCC stage, T-stage, and postoperative adjuvant therapy. The predictive model showed that the 3-year AUC was 0.787, 5-year AUC was 0.806, and C-index was 0.766. Compared to non-SRC patients, patients with SRC had a better prognosis in EGC [hazard ratio (HR): 0.626, 95% confidence interval (CI): 0.427-0.919, P < 0.05] and a worse prognosis in AGC (HR: 1.139, 95%CI: 1.030-1.258, P < 0.05). When non-SRC was divided into differentiated and undifferentiated types for comparison, it was found that in EGC, SRC had a better prognosis than differentiated and undifferentiated types, while there was no significant difference between differentiated and undifferentiated types. In AGC, there was no significant difference in prognosis between SRC and undifferentiated types, both of which were worse than differentiated types. A prognostic analysis of postoperative adjuvant therapy for SRC in patients with AGC revealed that adjuvant postoperative radiotherapy or chemotherapy significantly improved patient survival (34.6% and 36.2% vs 18.6%, P < 0.05).CONCLUSIONThe prognosis of SRC is better than that of undifferentiated type, especially in EGC, and its prognosis is even better than that of differentiated type. SRC patients can benefit from early detection, surgical resection, and aggressive adjuvant therapy.

Clinical features and prognostic factors of esophageal signet ring cell carcinoma: construction and validation of a model based on the SEER database.

Signet ring cell carcinoma (SRCC) of the esophagus is a rare subtype of esophagus cancer with a poor prognosis. Our study aimed to determine the prognostic factors and establish nomograms to predict overall survival (OS) and cancer-specific survival (CSS) for patients with esophageal SRCC. A total of 401 esophageal SRCC patients were identified from Surveillance Epidemiology and End Results (SEER) database and randomly divided into training and validation groups. We integrated the significant prognostic factors identified by multivariate cox analysis and construct nomograms to predict 2- and 5-year OS and CSS. Then, we evaluated the performance of the nomograms through concordance index (C-index), calibration curve, and the area under the curve (AUC) of the receiver operating characteristic curve. Multivariate Cox analysis revealed that American Joint Committee on Cancer (AJCC) stage, chemotherapy and surgery were associated with both OS and CSS. The C-indexes for OS and CSS predicted nomograms were 0.773 and 0.806, respectively. The calibration curves demonstrated good agreement between the actual observation and the nomogram prediction. Furthermore, the novel nomograms displayed higher AUC values in predicting OS and CSS compared to the 7th Tumor-Node-Metastasis (TNM) staging system. AJCC stage, chemotherapy and surgery were independent prognostic factors in esophageal SRCC patients. The proposed three-factor nomogram can assist clinicians predict the accurate prognosis of esophageal SRCC, thus contributing to individualized clinical practice.

Clinicopathological Features and Prognostic-Related Risk Factors of Gastric Signet Ring Cell Carcinoma: A Meta-Analysis.

Background Gastric signet ring cell carcinoma (SRCC) has shown a growth growing trend worldwide, but its clinicopathological features and prognostic-related risk factors have not been systematically studied. This systematic review was devoted to this. Method PubMed, Embase, Cochrane Library, and Web of Science databases were retrieved, and retrospective cohort studies comparing clinicopathological features and related risk factors in SRCC patients were included. Results In SRCC patient population, males were more than females (male, OR = 1.38, 95% CI: 1.20-1.60); N3 patients were more than N0-2 patients (N0-2, OR = 3.19, 95% CI: 1.98-5.15); M1 patients were more than M0 patients (M0, OR = 3.30, 95% CI: 1.88-5.80); patients with tumor > 5 cm were more than those with tumor (≤5 cm, OR = 7.36, 95% CI: 1.33-40.60). Patients with age < 60 years (age ≥ 60 years, OR = 1.03, 95% CI: 1.01-1.05), lymphatic vessel invasion (no, OR = 1.74, 95% CI: 1.03-2.45), T2 (T1, OR = 1.17, 95% CI: 1.07-1.28) and T4 (T1, OR = 2.55, 95% CI: 2.30-2.81) stages, and N1 (N0, OR = 1.73, 95% CI: 1.08-2.38), N2 (N0, OR = 2.24, 95% CI: 1.12-3.36), and N3 (N0, OR = 3.45, 95% CI: 1.58-5.32) stages had higher hazard ratio (HR). Conclusion SRCC may occur frequently in male. Age, lymphatic vessel invasion, TN, and M stage may be risk factors for poor prognoses of SRCC patients.

The Prognostic Significance and Gene Expression Characteristics of Gastric Signet-Ring Cell Carcinoma: A Study Based on the SEER and TCGA Databases.

PurposeThis study is based on the Surveillance, Epidemiology, and End Results (SEER) program to explore the prognostic differences between signet-ring cell carcinoma (SRC) and intestinal-type gastric carcinoma (ITGC). This study is also based on gene sequencing data from The Cancer Genome Atlas (TCGA) to identify unique genetic contributions to the prognostic differences between the two subtypes of gastric cancer.Patients and MethodsThe clinical data were based on the SEER database from 2004 to 2015. Kaplan–Meier (KM) curves were used to compare 5-year overall survival (OS), and Cox regression was used for univariate and multivariate analyses. Gene expression profiles were obtained from TCGA database, and differentially expressed genes (DEGs) were screened. Functional enrichment analysis, protein interaction and survival analysis will be further carried out. Genes of interest were verified by the Human Protein Atlas, immunohistochemistry, and encyclopedia of Cancer Cell Lines (CCLE). The relationship between genes of interest and immune cell infiltration was also analyzed by Tumor Immune Estimation Resource (TIMER).ResultsCompared with ITGC patients, SRC patients were more likely to be female, tended to be younger, and have a greater tumor distribution in the middle and lower stomach (p < 0.01). SRCs showed a significantly better prognosis than ITGCs (p < 0.01) in early gastric cancer (EGC), while the prognosis of SRCs was significantly worse than ITGCs (p < 0.05) in advanced gastric cancer (AGC). A total of 256 DEGs were screened in SRCs compared to ITGCs, and the enrichment analysis and protein interactions revealed that differential genes were mainly related to extracellular matrix organization. Thrombospondin1 (THBS1) and serpin peptidase inhibitor, clade E, member 1 (SERPINE1) are significantly differentially expressed between SRC and ITGC, which has been preliminarily verified by immunohistochemistry and open-source databases. THBS1 and SERPINE1 are also associated with multiple immune cell infiltrates in gastric cancer.ConclusionsThere were significant differences in the clinicopathological features and prognosis between SRC and ITGC. These results suggest that SRC and ITGC may be two distinct types of tumors with different pathogeneses. We found many codifferentially expressed genes and important pathways between SRC and ITGC. THBS1 and SERPINE1 were significantly differentially expressed in the two types of gastric cancer, and may have potentially important functions.

Construction of Novel Prognostic Nomogram for Mucinous and Signet Ring Cell Colorectal Cancer Patients with a Survival Longer Than 5 Years.

PurposeMucinous adenocarcinoma (MA) and signet ring cell carcinoma (SRCC) are aggressive colorectal cancer histological subtypes with dismal prognosis. This study investigated prognostic factors and constructed novel nomograms for MA and SRCC patients who survived for over 5 years to optimize the follow-up regime, especially for early-onset patients.Patients and MethodsData from the Surveillance, Epidemiology, and End Results (SEER) database registered between 2004 and 2018 were extracted. MA and SRCC patients were divided into two groups with survival time of 5 years as a cut-off point. Prognostic factors for overall survival (OS) and cancer-specific survival (CSS) were determined by Cox regression models, and survival curves were plotted by the Kaplan–Meier method.ResultsWe identified 8286 MA patients (45.73%) and 551 SRCC patients (20.32%) who survived for over 5 years. Multivariable Cox analyses identified age, tumor location, N stage, metastasis, CEA level, surgery, and lymph nodes dissection as independent risk factors for MACSS. SRCC was more aggressive and only N2 stage (P = 0.011) and metastasis (P = 0.043) were inversely associated with SRCCSS. Furthermore, we observed that small tumor size, well differentiation, and chemotherapy no longer provided survival benefit to ≥5-year survivors. Therefore, we constructed novel nomograms appropriate for MA patients who survived for over 5 years. The consistency indexes for predicting 10-year OS and CSS were respectively 0.717, 0.712 in the training cohort and 0.727, 0.735 in the validation cohort.ConclusionOur well-calibrated nomograms represent the first clinical prognostic models developed especially for MA patients with a survival longer than 5 years. For both MA and SRCC patients, TNM stage was a stable prognostic factor, while the prognostic values of tumor size, differentiation grade, and chemotherapy changed over time. We are hopeful that our prognostic models will help define personalized follow-up managements to further prolong patient survival.

Deep learning-based AI model for signet-ring cell carcinoma diagnosis and chemotherapy response prediction in gastric cancer.

We aimed to develop a noninvasive artificial intelligence (AI) model to diagnose signet-ring cell carcinoma (SRCC) of gastric cancer (GC) and identify patients with SRCC who could benefit from postoperative chemotherapy based on preoperative contrast-enhanced computed tomography (CT). A total of 855 GC patients with 855 single GCs were included, of which 249 patients were diagnosed as SRCC by histopathologic examinations. The AI model was generated with clinical, handcrafted radiomic, and deep learning features. Model diagnostic performance was measured by area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, while predictive performance was measured by Kaplan-Meier curves. In the test cohort (n=257), the AUC, sensitivity, and specificity of our AI model for diagnosing SRCC were 0.786 (95% CI: 0.721-0.845), 77.3%, and 69.2%, respectively. For the entire cohort, patients with AI-predicted high risk had a significantly shorter median OS compared with those with low risk (median overall survival [OS], 38.8vs. 64.2 months, p=0.009). Importantly, in pathologically confirmed advanced SRCC patients, AI-predicted high-risk status was indicative of a shorter overall survival (median overall survival [OS], 31.0 vs. 54.4 months, p=0.036) and marked chemotherapy resistance, whereas AI-predicted low-risk status had substantial chemotherapy benefit (median OS [without vs. with chemotherapy], 26.0 vs. not reached, p=0.013). The CT-based AI model demonstrated good performance for diagnosing SRCC, stratifying patient prognosis, and predicting chemotherapy responses. Advanced SRCC patients with AI-predicted low-risk status may benefit substantially from adjuvant chemotherapy.

Prognostic Analysis of Primary Breast Signet Ring Cell Carcinoma and Mucinous Breast Adenocarcinoma: A SEER Population-Based Study.

BackgroundPrimary breast signet ring cell carcinoma (SRCC) is a rare type of breast cancer with typical morphological characteristics, high aggressiveness, and poor prognosis. SRCC is different from mucinous breast adenocarcinoma (MBC). However, only a few studies have explored the clinicopathological features and prognosis of SRCC and MBC.MethodsData retrieved from the Surveillance, Epidemiology, and End-Results (SEER) database (2004–2015) were used to explore the prognostic effect of clinicopathological features and treatment modalities on survival outcomes of SRCC and MBC patients. Kaplan–Meier plot analysis, multivariate Cox proportional risk model, propensity score matching (PSM), and subgroup analysis were performed.ResultsA total of 167 patients with SRCC and 11,648 patients with MBC were included in the study. SRCC patients exhibited higher histological grade (p < 0.001), larger tumor volume (p < 0.001), higher rate of lymph node metastasis (p < 0.001), and higher frequency of distal metastasis (p < 0.001) compared with MBC patients. Cox proportional hazards regression analysis showed that SRCC patients had lower overall survival (OS) and breast cancer-specific survival (BCSS) compared with MBC patients. Subgroup survival analysis showed that the SRCC patients had lower OS and BCSS in subgroups including younger than 60 years old, white race, married, without chemotherapy, and received radiotherapy compared with the MBC patients in these subgroups. In addition, the SRCC patients had lower BCSS in subgroups including other races (including Asian or Pacific Islander and American Indian/Alaska Native), without surgery, and lymph node metastasis.ConclusionThe findings showed that primary breast SRCC patients have unique clinical characteristics and worse prognosis compared with MBC patients. Notably, different treatment methods resulted in different prognosis for SRCC and MBC types; therefore, SRCC patients should be distinguished from MBC patients to improve efficacy of treatment.

Glutathione-dependent system in the blood of gastric cancer patients with various tumor histotypes and prevalence of the disease

Purpose of the study. Exploring the erythrocyte glutathione system functioning in patients with gastric cancer in a comparative aspect, depending on tumor histotype and disease prevalence.Patients and methods. The study included 89 patients with gastric cancer, divided into 6 groups depending on the histotype of the tumor. Separately, the results of the study were analyzed in patients with T4 status according to TNM and in patients at stage 4. The content of reduced glutathione and the activity of glutathione-dependent enzymes in the erythrocytes of the patients' blood were studied by conventional spectrophotometric methods. Statistical processing of the results was carried out using the Statistika 6.0 software package according to the Student's t-test and the nonparametric Wilcoxon-Mann-Whitney test for two independent samples.Results. An increase in the content of glutathione was revealed in patients with gastric cancer compared with the group without oncopathology. The maximum increase was observed in patients with low-grade adenocarcinoma - by 42.5 %, while in signet ring cell carcinoma (SRCC) there was only a tendency to increase by 17.8 %. Glutathione reductase activity was decreased in adenocarcinoma by 23.4-26.2 % and did not change in SRCC. The activity of the antioxidant enzymes glutathione peroxidase and glutathione transferase was increased in all groups, and especially in SRCC - by 76 % and 23-29 %, respectively. In patients with the T4 status and at stage IV of the process, a lower activity of the studied glutathione-dependent enzymes was revealed in comparison with all other groups of patients.Conclusions. The data obtained indicate a greater functional potential of the glutathione system in SRCC. A significant increase in glutathione transferase activity at a sufficiently high level of reduced glutathione can contribute to the development of treatment resistance in SRCC patients.