Although microsatellite stability/Epithelial-mesenchymal transition (MSS/EMT) subtypes have been reported in multiple cancer prognosis studies, strong confounding factors between MSS/EMT (usually with Lauren's diffuse phenotype) and diffuse gastric cancer (GC) may obscure the independent prognostic value of diffuse GC. Additionally, recent studies suggest a strong correlation between mural stratification based on CT and diffuse GC. This study aims to investigate potential prognostic factors of MSS diffuse GC using mural stratification and to develop a risk assessment model.

This retrospective study included 131 patients with MSS diffuse GC who underwent radical surgery. Univariate and multivariate Cox proportional hazards regression analysis was used to identify model predictors and construct a nomogram for overall survival (OS) and recurrence-free survival (RFS) risks. The model's performance was evaluated using ROC, accuracy, and C-index. Internal validation of the model was conducted using the bootstrap resampling method.

Among 131 cases, 60 cases (45.8%) exhibited grade 2 mural stratification, which correlated with a poorer tumor prognosis and a more invasive phenotype. Furthermore, a nomogram for predicting OS and RFS prognosis was established based on multivariate results (age, extranodal invasion, mural stratification, and/or P53). The nomogram demonstrated excellent performance, with an AUC of 0.859 (95% CI 0.794-0.924) for OS and 0.859 (95% CI 0.789-0.929) for RFS. Internal validation using 1000 bootstrap samples yielded AUC values of 0.845 and 0.846 for OS and RFS, respectively.

Grade 2 mural stratification based on CT imaging revealed a more aggressive invasive phenotype, characterized by increased LN metastasis, higher rates of peritoneal metastasis, and a poorer short-term prognosis. Furthermore, the CT phenotype-based nomogram demonstrates favorable discrimination and calibration, enabling convenient individual short-term prognostic evaluation following resection of MSS diffuse GC.

Heterogeneity of gastric cancer (GC) is the main trigger of the disease's relapse. The aim of this study was to investigate the connections between targeted genes, cancer clinical features, and the effectiveness of FLOT chemotherapy. Twenty-one patients with gastric cancers (GCs) were included in this study. Tumor-targeted sequencing was conducted, and real-time PCR was used to assess the expression of molecular markers in tumors. Seven patients with stabilization had mutations that were related to their response to therapy and were relevant to the tumor phenotype. Two patients had two mutations. The number of patients with TP53 mutations increased in HER2-positive tumor status. PD-L1-positive cancers had mutations in KRAS, TP53, PIK3CA, PTEN, and ERBB, which resulted in an increase in PD-1 expression. TP53 mutation and PTEN mutation are associated with changes in factors associated with neoangiogenesis. In concusion, patients who did not have aggressive growth markers that were verified by molecular features had the best response to treatment, including complete morphologic regression.

Background: Although the prognostic value of the epithelial-to-mesenchymal transition (EMT) in gastric cancer has been reported in several studies, the strong association with the diffuse type may represent a confounding factor. Our aim is to investigate potential correlations among EMT status, tumor advancement, and prognosis in diffuse gastric cancer. Methods: Between 1997 and 2012, 84 patients with microsatellite-stable (MSS) diffuse-type tumors underwent surgery. The EMT phenotype was assessed with the E-cadherin, CD44, and zinc finger E-box binding homeobox 1 (ZEB-1) immunohistochemical markers. Results: Forty-five out of 84 cases (54%) were EMT-positive; more advanced nodal status (p = 0.010), pTNM stage (p = 0.032), and vascular invasion (p = 0.037) were observed in this group. The median numbers of positive nodes (13 vs. 5) and involved nodal stations (4 vs. 2) were higher in the EMT-positive group. The cancer-related survival time was 26 months in EMT-positive cases vs. 51 in negative cases, with five-year survival rates of 17% vs. 51%, respectively (p = 0.001). The EMT status had an impact on the prognosis of patients with <70 years, R0 resections, or treatment with adjuvant chemotherapy. Tumor relapses after surgery and peritoneal spread were significantly higher in the EMT-positive tumors. Conclusions: EMT status, when assessed through immunohistochemistry, identified an aggressive phenotype of MSS diffuse-type tumors with extensive lymph nodal spread, peritoneal dissemination, and worse long-term outcomes.

Gastric cancer (GC) molecular heterogeneity represents a major determinant for clinical outcomes, and although new molecular classifications have been introduced, they are not easy to translate from bench to bedside. We explored the data from GC public databases by performing differential gene expression analysis (DEGs) and gene network reconstruction to identify master regulators (MRs), as well as a gene set analysis (GSA) to reveal their biological features. Moreover, we evaluated the association of MRs with clinicopathological parameters. According to the GSA, the Diffuse group was characterized by an epithelial-mesenchymal transition (EMT) and inflammatory response, while the Intestinal group was associated with a cell cycle and drug resistance pathways. In particular, the regulons of Diffuse MRs, such as Vgll3 and Ciita, overlapped with the EMT and interferon-gamma response, while the regulons Top2a and Foxm1 were shared with the cell cycle pathways in the Intestinal group. We also found a strict association between MR activity and several clinicopathological features, such as survival. Our approach led to the identification of genes and pathways differentially regulated in the Intestinal and Diffuse GC histotypes, highlighting biologically interesting MRs and subnetworks associated with clinical features and prognosis, suggesting putative actionable candidates.

Signet ring cells (SRC) are widely acknowledged as a prognostically unfavorable histotype amongst poorly cohesive gastric cancer. In this study we evaluated the impact of SRC percentage on the clinical, pathological and prognostic features of these tumors according to the classification by the European Chapter of the IGCA.

We retrospectively reviewed records of patients with poorly cohesive gastric cancer that underwent surgery between 1995 and 2016, whose tissue specimens were available in a biological bank. All slides were put under revision, patients were reclassified into three groups according to the proportion of signet ring cells: "pure" SRC (containing ≥90% of SRCs), Poorly Cohesive-Not Otherwise Specified (PC-NOS) (containing ≤10% of SRCs), and PC-NOS/SRC (containing <90% but >10% of SRCs). The clinicopathological factors between different types were analyzed and prognostic differences were compared.

Among 143 enrolled patients, 51% were male and 49% were female. The mean (±SD) age at diagnosis was 61 ± 13.9 years. Eighty-seven patients (60.8%) were reclassified as PC-NOS, 56 (39.2%) as PC-NOS/SRC and none as "pure" SRC. Five-years overall survival was significantly higher in PC-NOS/SRC group (63.3%) compared with PC-NOS group (12.7%). The increase in mortality risk was more than four-fold in patients with PC-NOS pattern compared to those with PC-NOS/SRC (HR 4.32 [95% CI 2.5-7.4]. After adjustment for potential confounding factors, SRC pattern was still an independent predictor of survival.

The percentage of SRCs is inversely related to tumor aggressiveness, confirming the role of SRC pattern as an independent predictor of survival.

The prevalence of diffuse-type gastric cancer (GC), especially signet ring cell carcinoma (SRCC), has shown an upward trend in the past decades. This study aimed to develop computed tomography (CT) based radiomics nomograms to distinguish diffuse-type and SRCC GC preoperatively.

A total of 693 GC patients from two centers were retrospectively analyzed and divided into training, internal validation and external validation cohorts. Radiomics features were extracted from CT images, and the Lauren radiomics model was established with a support vector machine (SVM) classifier to identify diffuse-type GC. The Lauren radiomics nomogram integrating radiomics features score (Rad-score) and clinicopathological characteristics were developed and evaluated regarding prediction ability. Further, the SRCC radiomics nomogram designed to identify SRCC from diffuse-type GC was developed and evaluated following the same procedures.

Multivariate analysis revealed that Rad-scores was significantly associated with diffuse-type GC and SRCC (p < 0.001). The Lauren radiomics nomogram showed promising prediction performance with an area under the curve (AUC) of 0.895 (95%CI, 0.957-0.932), 0.841 (95%CI, 0.781-0.901) and 0.893 (95%CI, 0.831-0.955) in each cohort. The SRCC radiomics nomogram also showed good discrimination, with AUC of 0.905 (95%CI,0.866-0.944), 0.845 (95%CI, 0.775-0.915) and 0.918 (95%CI, 0.842-0.994) in each cohort. The radiomics nomograms showed great model fitness and clinical usefulness by calibration curve and decision curve analysis.

Our CT-based radiomics nomograms had the ability to identify the diffuse-type and SRCC GC, providing a non-invasive, efficient and preoperative diagnosis method. They may help guide preoperative clinical decision-making and benefit GC patients in the future.

Gastric cancer (GC) is the fifth most common cancer and the third cause of cancer-related deaths worldwide. In western countries, more than half of GC patients are diagnosed at advanced stages and 5-year survival rates range between 20-30%. The only curative treatment is surgery, and despite recent advances in oncological therapies, GC prognosis is still poor. The main prognostic tool for patient categorization and treatment selection is the TNM classification, but its limitations are being increasingly recognized. Early recurrences may occur in early-stage disease, and patients at the same stage show heterogeneous outcomes. Thus, there is a need to improve GC stratification and to identify new prognostic factors, which may allow us to select drug-susceptible populations, refine patient grouping for clinical trials and discover new therapeutic targets. Molecular classifications have been developed, but they have not been translated to the clinical practice. On the other hand, histological assessment is cheap and widely available, and it is still a mainstay in the era of molecular medicine. Furthermore, histological features are acquiring new roles as reflectors of the genotype-phenotype correlation, and their potential impact on patient management is currently being analyzed. The aim of this literature review is to provide a modern overview of the histological assessment of GC. In this study, we discuss recent topics on the histological diagnosis of GC, focusing on the current role of Laurén classification and the potential value of new histological features in GC, such as inflammatory infiltration and tumor budding.

Genetic and epigenetic alterations have been under concentrated investigations for many years in order to unearth the molecules regulating human cancer pathogenesis. However, the identification of a wide range of dysregulated genes and their protein products has raised a question regarding how the results of this large collection of alterations could converge into a formation of one malignancy. The answer may be found in the signaling cascades that regulate the survival and metabolism of the cells. Aberrancies of each participant molecule of such cascades may well result in augmented viability and unlimited proliferation of cancer cells. Among various signaling pathways, the phosphatidylinositol-3-kinase (PI3K) axis has been shown to be activated in about one-third of human cancers. One of the malignancies that is mostly affected by this axis is gastric cancer (GC), one of the most fatal cancers worldwide. In the present review, we aimed to illustrate the significance of the PI3K/Akt/mTOR axis in the pathogenesis of GC and also provided a wide perspective about the application of the inhibitors of this axis in the therapeutic strategies of this malignancy.

The impact of negative lymph nodes (LNs) on survival of pN+ patients has been recognized. The weight of negative LNs in an inverse lymph node ratio (nR) should be related to its prognostic impact. Five hundred and two consecutive gastric cancer patients, who underwent radical gastrectomy, were included. Patients were split into groups according to the number of harvested nodes and a cross-tabulation with pTNM stages was performed to test differences in the tumor burden. pN+ patients (n = 296) were split into groups of negative LNs harvested. We tested an alternative formula for computing a lymph node ratio: nR = total number of harvested nodes/total number of positive nodes. The median number of negative LNs was significantly different (p < 0.01) between dissection groups, but not the median of positive nodes (p > 0.05). No difference in pTNM percentage distribution was found between these groups (p > 0.05). When tested, the overall survival improved significantly for groups with larger numbers of negative LNs (p < 0.001). A cutoff of nR ≥ 6 was an independent prognostic factor for survival (p = 0.001), and the survival of pN+ patients with nR ≥ 6 was not different from pN0 patients. The impact of the number of negative LNs on the survival of the pN+ patients was demonstrated. The higher numbers in the numerator of the nR was due to the disproportion between harvested negative LNs and metastatic LNs. Larger ratios imply more negative lymph nodes in relation to positive lymph nodes, which was significantly associated with survival. We believe that the proposed nR is a friendlier to use format because of its intuitive interpretation.

Surgical quality assurance is a key element of gastric cancer treatment. The Maruyama Computer Program (MCP) allows to predict lymph node involvement in stations no. 1-16. The aim of the current study was to evaluate the accuracy of the MCP predictions in GC patients treated with neoadjuvant chemotherapy (nCTH) followed by gastrectomy with adequate lymphadenectomy.

101 patients who underwent preoperative nCTH followed by D2 gastrectomy with curative intent were analysed. The response to nCTH was measured using the tumour regression grade system.

Test sensitivity, specificity, PPV, NPV and accuracy of the MCP were 92%, 33%, 41%, 89%, and 53%, respectively. In patients with response to nCTH, number of false positive (FP) results was significantly higher than in patients who did not respond to nCTH both in the N1 (56.3% vs 28.9%, p < 0.0001) and in the N2 (59% vs 41%, p < 0.0001) trier. The risk for FP results was 6 times higher in N1 (OR = 6.50, 95%CI: 3.91-10.82,; p < 0.0001) and N2 (OR = 5.84, 95%CI: 2.85-11.96; p < 0.0001) triers. In patients with intestinal type GC, the risk for FP results was 4 times higher than in other histologic types of GC in both N1 (OR = 4.23, 95%CI: 2.58-6.95; p < 0.0001) and N2 (OR = 4.23, 95%CI: 2.02-9.62; p = 0.0002) triers.

MCP predictions in the GC patients treated with nCTH have low specificity due to significantly high number of FP results. Noticeably low accuracy level of predictions indicate a need for new prediction models, based on Laurén classification, since it may provide some information on expected regression grade.

The insulin-like growth factor (IGF) system, which is constituted by the IGF-1 and IGF-2 peptide hormones, their corresponding receptors and several IGF binding proteins, is involved in physiological and pathophysiological processes. The IGF system promotes cancer proliferation/survival and its signaling induces the epithelial-mesenchymal transition (EMT) phenotype, which contributes to the migration, invasiveness, and metastasis of epithelial tumors. These cancers share two major IGF-1R signaling transduction pathways, PI3K/AKT and RAS/MEK/ERK. However, as far as we could review at this time, each type of cancer cell undergoes EMT through tumor-specific routes. Here, we review the tumor-specific molecular signatures of IGF-1-mediated EMT in breast, lung, and gastric cancers.