• Gastric cancer
• Linear model
• Machine learning
• Signet ring cell cancer

• Humans
• Stomach Neoplasms/surgery
• Stomach Neoplasms/pathology
• Stomach Neoplasms/mortality
• Carcinoma, Signet Ring Cell/surgery
• Carcinoma, Signet Ring Cell/pathology
• Carcinoma, Signet Ring Cell/mortality
• Male
• Female
• Machine Learning
• Middle Aged
• Aged
• Prognosis
• Gastrectomy/methods
• Neoplasm Recurrence, Local/epidemiology
• Neoplasm Recurrence, Local/pathology
• Lymphatic Metastasis
• Survival Rate
• Adult
• Retrospective Studies
• Lymph Node Excision
• Linear Models
• Aged, 80 and over
• Neoplasm Staging

• Diffuse gastric cancer
• Gastric cancer
• Oesophageal cancer
• Poorly cohesive gastric cancer
• Signet ring cell carcinoma

• esophagogastric cancer
• esophagogastric neoplasm
• meta-analysis
• neoadjuvant chemotherapy
• signet ring cell carcinoma (SRCC)
• systematic review

• Gastric cancer
• Immunotherapy
• Molecular targeted therapy

• CDH1
• E-Cadherin
• EZH2
• cancer subtyping
• diffuse-type gastric adenocarcinoma
• gastric cancer
• gastric organoids
• immune evasion
• immune landscape remodeling
• single-cell transcriptomics

• P30 CA016672 NCI NIH HHS
• P30 EY002520 NEI NIH HHS
• S10 OD023469 NIH HHS
• S10 OD025240 NIH HHS

• Differentiation
• Intestines
• Smooth muscle tumour
• Stomach

• gastric cancer
• poorly cohesive carcinoma
• signet ring cell

• early-onset gastric cancer patients
• gastric cancer in young patients
• german clinical cancer registry group

• Carcinoma, Signet Ring Cell
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Retrospective Studies
• Risk Factors
• Stomach Neoplasms

• chemotherapy
• deep learning
• diagnosis
• signet-ring cell carcinoma
• survival

Introduction: The aim of this study was to perform a clinicopathologic analysis of PHLPP1 expression in gastric cancer patients and analyze AKT activity with chemotherapy drug treatment in cancer subtypes. Materials and Methods: Surgically resected gastric cancer tissue specimens were obtained from 309 patients who underwent gastrectomy, and PHLPP1 expression was validated by tissue microarray analysis with immunohistochemistry. We assessed whether PHLPP1 selectively dephosphorylates Ser473 of AKT in an in-vitro study. Results: We found that the PHLPP1 overexpression (OE) group showed significantly greater proportions of differentiated subtype samples and early T stage samples, lower lymph node metastasis, and lower TNM stage than the PHLPP1 underexpression (UE) group. The overall survival of the PHLPP1-OE group was significantly higher (53.39 ± 0.96 months) than that of the PHLPP1-UE group (47.82 ± 2.57 months) (P = .01). In vitro analysis, we found that the PHLPP1-OE group showed a significant decrease in relative AKT S-473 levels in both cell lines (MKN-74 and KATO-III). We found that treatment with chemotherapy drugs decreased the activity of Ser473 in the MKN-74 cell line with PHLPP1 OE, but it did not affect the activity of Ser473 in KATO-III cells. Conclusion: We found that patients who overexpressed PHLPP1 showed low recurrence and good prognosis. PHLPP1 was found to work by lowering the activity of AKT Ser473 in gastric cancer. Additionally, we found a clue regarding the mechanism of chemotherapeutic drug resistance in a cell line of signet ring cell origin and will uncover this mechanism in the future.

• NGS
• biomarker
• immunohistochemistry
• prognosis
• stomach neoplasm

The clinical significance of signet ring cells (SRCs) in surgical esophageal and esophagogastric junction adenocarcinoma (EEGJA) remains unclear now.

To explore the association between the presence of SRCs and the clinicopathological and prognostic characteristics in surgical EEGJA patients by combining and analyzing relevant studies.

The PubMed, Web of Science, and EMBASE electronic databases were searched for the relevant literature up to March 28, 2021. The relative risk (RR) with 95% confidence interval (CI) was calculated to assess the relationship between SRCs and clinicopathological parameters of surgical EEGJA patients, and the hazard ratio (HR) with 95%CI was calculated to explore the impact of SRC on the prognosis. All statistical analyses were conducted with STATA 12.0 software.

A total of ten articles were included, involving 30322 EEGJA patients. The pooled results indicated that the presence of SRCs was significantly associated with tumor location (RR: 0.76, 95%CI: 0.61-0.96, P = 0.022; I² = 49.4%, P = 0.160) and tumor-node-metastasis stage (RR: 1.30, 95%CI: 1.02-1.65, P = 0.031; I² = 73.1%, P = 0.002). Meanwhile, the presence of SRCs in surgical EEGJA patients predicted a poor overall survival (HR: 1.36, 95%CI: 1.12-1.65, P = 0.002; I² = 85.7%, P < 0.001) and disease-specific survival (HR: 1.86, 95%CI: 1.55-2.25, P < 0.001; I² = 63.1%, P = 0.043).

The presence of SRCs is related with advanced tumor stage and poor prognosis and could serve as a reliable and effective parameter for the prediction of postoperative survival and formulation of therapy strategy in EEGJA patients. However, more high-quality studies are still needed to verify the above findings.

• Signet ring cells
• Esophageal and esophagogastric junction adenocarcinoma
• Clinicopathological characteristics
• Prognosis
• Systematic review
• Meta-analysis

There has been an increase in the incidence of signet ring cell cancer (SRCC) of the stomach and gastro-esophageal junction (GEJ). The multistage carcinogenesis involving genetic and epigenetic aberrations may have a major role in the increasing incidence of SRCC. Although there are numerous studies on the prognostic value of SRCC, they are markedly inconsistent in their results, making it impossible to draw any meaningful conclusions. We aimed to examine the available evidences on molecular alterations and stage-stratified treatment approaches in SRCC of the stomach and GEJ.

A systematic search was carried out in PubMed. Studies available in English related to SRCC of stomach and gastro-esophageal junction were identified and evaluated.

This study reviewed the current evidence and provided an insight into the molecular alterations, stage-stratified treatment approaches, and future challenges in the management of SRCC of the stomach and GEJ. Specific therapeutic strategies and personalized multimodal treatment have been recommended based on the tumor characteristics of SRCC.

Multistage carcinogenesis involving genetic and epigenetic aberrations in SRCC is interlinked with stage-dependent prognosis. Specific therapeutic strategy and personalized multimodal treatment should be followed based on the tumor characteristics of SRCC. Endoscopic resection, radical surgery, and perioperative chemotherapy should be offered in carefully selected patients based on stage and prognostic stratification. Future studies in genetic and molecular analysis, histopathological classification, and options of multimodality treatment will improve the prognosis and oncological outcomes in SRCC of gastric and GEJ.

• E-cadherin
• Gastro-esophageal junction cancer
• Molecular alterations
• Signet ring cell cancer
• Stage-stratified treatment
• Stomach cancer

• adenocarcinoma
• gastric cancer
• histopathology
• signet ring cell carcinoma

• Gastric cancer
• Lymph node metastasis
• No.12a lymph node
• Prognosis
• The 8th edition staging system

• Diffuse
• cancer
• gastric

• PD-L1
• advanced GC
• genetic alterations
• meta-analysis
• prognostic factor review
• recurrence pattern
• signet-ring cell

Background  We report an extremely unusual case of anterior clinoid process (ACP) metastasis as the first presentation of a signet ring cell carcinoma.

Case Description  A 54-year-old female patient presented with right-sided visual disturbances due to optic nerve compression from a computed tomography (CT)-identified right anterior clinoid bone lesion. Contrast-enhanced magnetic resonance imaging showed an extra-axial, well-bordered enhancing mass extending from the right ACP toward the inner lumen of the optic canal. Pterional approach was adopted to remove the lesion and decompress the optic canal. Histological examination demonstrated a metastasis from a signet ring cell carcinoma. Postoperative CT showed near-total resection of the tumor and decompression of the optic canal. Visual defect remained unchanged.

Conclusion  Metastasis should be considered in the differential diagnosis of the ACP lesions. The early suspicion and identification of this extremely rare pathological entity can be helpful for the prompt management of patients, especially in the absence of any other signs of oncological diseases.

• anterior clinoid process
• metastasis
• signet ring cell carcinoma

The purpose of this study was to explore the role of different undifferentiated components in the lymph node metastasis (LNM) of early mixed gastric cancer.

A total of 1596 patients with EGC who underwent gastrectomy were divided into four types: pure differentiated (PD), pure poorly differentiated (Poorly D), pure signet ring cell carcinoma (SRC), and mixed. Mixed type was classified into four subtypes: differentiated-predominant type mixed with poorly differentiated component (MD-P), poorly differentiated-predominant type mixed with differentiated component (MP-D), differentiated-predominant type mixed with SRC component (MD-S), and poorly differentiated-predominant type mixed with SRC component (MP-S). We analyzed the clinicopathological differences between all types and the rates of LNM of patients fulfilling endoscopic submucosal dissection (ESD) criteria.

LNM was more common in mixed (21.9%) than in PD (7.5%, P < 0.001) or SRC (11.3%, P < 0.001). When analyzed the subgroups of mixed type, LNM was more frequent in MD-P (15.4%) than in PD (7.5%, P = 0.003). LNM in MD-S (7.4%, P = 1.000) was not higher than in PD. MP-S (24.5%) showed a higher rate of LNM than SRC (11.3%, P < 0.001) rather than Poorly-D (22.7%, P = 0.681). For lesions satisfying ESD criteria, MD-S (0%, P = 1.000), and MD-P (5.9%, P = 0.12) did not have higher rates of LNM than PD (1.4%).

The presence of poorly differentiated component but not SRC increases the LNM rate of mixed type. ESD is recommended for the treatment of MD-S and MD-P consistent with ESD criteria.

• Gastric cancer
• Lymph node metastasis
• Signet ring cell carcinoma

• Gastric cancer
• Micro-RNA-99a-5p
• Prognosis
• Proliferation
• Signet-ring cell carcinoma

Our aims were to establish novel nomogram models, which directly targeted patients with signet ring cell carcinoma (SRC), for individualized prediction of overall survival (OS) rate and cancer-specific survival (CSS).

We selected 1,365 SRC patients diagnosed from 2010 to 2015 from Surveillance, Epidemiology and End Results (SEER) database, and then randomly partitioned them into a training cohort and a validation cohort. Independent predicted indicators, which were identified by using univariate testing and multivariate analyses, were used to construct our prognostic nomogram models. Three methods, Harrell concordance index (C-index), receiver operating characteristics (ROC) curve and calibration curve, were used to assess the ability of discrimination and predictive accuracy. Integrated discrimination improvement (IDI), net reclassification improvement (NRI) and decision curve analysis (DCA) were used to assess clinical utility of our nomogram models.

Six independent predicted indicators, age, race, log odds of positive lymph nodes (LODDS), T stage, M stage and tumor size, were associated with OS rate. Nevertheless, only five independent predicted indicators were associated with CSS except race. The developed nomograms based on those independent predicted factors showed reliable discrimination. C-index of our nomogram for OS and CSS was 0.760 and 0.763, which were higher than American Joint Committee on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) staging system (0.734 and 0.741, respectively). C-index of validation cohort for OS was 0.757 and for CSS was 0.773. The calibration curves also performed good consistency. IDI, NRI and DCA showed the nomograms for both OS and CSS had a comparable clinical utility than the TNM staging system.

The novel nomogram models based on LODDS provided satisfying predictive ability of SRC both in OS and CSS than AJCC 8th edition TNM staging system alone.

• Log odds of positive lymph nodes
• nomograms
• prognosis
• signet ring cell

• Gastrectomy
• Gastric cancer
• Signet ring cell adenocarcinoma

Age is a prognostic factor for multiple malignancies. In this study, we aimed to assess the effect of age on the cancer-specific survival (CSS) of patients with gastric signet-ring cell carcinoma (SRC).

Information on patients with gastric SRC was extracted from the Surveillance, Epidemiology, and End Results database. Chi-squared tests were used to demonstrate distribution differences, and Kaplan-Meier analysis and Cox regression models were used to analyze the impact of age on CSS.

A total of 4596 patients were enrolled and divided into 3 subgroups according to age (<45, 45–74, and >74 years old). Higher percentages of T4, N2, and M1 disease were observed in the <45-year-old group (all P<0.001). Kaplan-Meier plots showed that the youngest group had the most favorable 5-year CSS rate (36.3%), which remained true after stratification according to tumor stage. Multivariate Cox regression models demonstrated a poorer survival outcome for >74-year-old than for <45-year-old patients (hazard ratio 1.841, 95% confidence interval 1.636–2.071; P<0.001).

Young age is associated with improved survival, even though younger patients generally present with a more advanced-stage disease.