The role of E-cadherin expression in the treatment of western undifferentiated early gastric cancer: Can a biological factor predict lymph node metastasis?

Background and Aim: Cell adhesion molecules (often referred to as cadherins) are glycoproteins found in the cell membrane. They regulate biological processes such as cell migration, differentiation, proliferation, and death (apoptosis). Her-2 is a proto-oncogene that belongs to the EGFR protein family. In cellular processes such as cell growth, regulates cellular activities such as proliferation, differentiation, and survival. This study aimed to determine the expression of E-cadherin and HER2 in the available histologic subtypes and evaluate if there is a correlation between E-cadherin and HER2 immunohistochemical expression in gastric carcinoma. Subjects & Methods: A total of 50 cases of stomach cancer were included in this study, all of which were obtained retrospectively between January 2017 and January 2020 from the Pathology Department, Tanta University, Egypt and Tanta Cancer Center archives. The samples were obtained from gastroplastectomy specimens then stained using the immunostaining approach described as follows: Deparaffinization and rehydration followed by using 3-hydroxy-4-napthylbenzaldehyde (3-OH-4-NHB) as a starting material then a smorgasbord of antigens then exposing to primary antibodies then exposing to a secondary biotinylated antibody, after that identifying of enzymes using streptavidin-labeled enzymes then preparing a color working reagent and last complexity in the development of color. Results: E-cadherin was statistically significantly high in tumors exhibiting aggressive clinicopathologic characteristics specifically in males, all histopathologic variants (except for poorly differentiated tubular adenocarcinoma and signet ring carcinoma), N stages, M stages, higher in absent vascular invasion cases but lower in present cases and the same with perineural invasion cases. Tumor site had no significant impact on the levels of E-cadherin. HER2 showed statistically insignificant correlations with all factors. E-cadherin and HER2 expression showed statistically insignificant relationship. Conclusion: Elevated E-cadherin expression is associated with tumors that exhibit aggressive clinicopathologic characteristics. HER2 was expressed positively in low-grade variants, but no correlation was established with clinical characteristics. E-cadherin and HER2 expression have no discernible relationship.

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“…Prior to this study, we noticed no correlation between tumor location and abnormal E-cadherin expression, which Piccolo et al [22] also detected.…”

Section: Discussioncontrasting

confidence: 46%

The Expression of E-cadherin & HER2 in Gastric Carcinoma

El-Mihy

Hasby

Noseir

et al. 2022

JAMMR

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“…GC incidence and mortality remain high [19]. With recent advances in the fields of molecular and cell biology, the understanding of molecular mechanisms underlying cancer has advanced considerably.…”

Section: Discussionmentioning

confidence: 99%

miR-874 inhibits gastric cancer cell proliferation by targeting SPAG9

Sun

Yin

et al. 2020

BMC Cancer

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Background: microRNAs (miRNAs) play essential roles in the development and progression of gastric cancer (GC). Although aberrant miR-874 expression has been reported in various human cancers, its role in GC remains obscure. Methods: miR-874 expression was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) in 62 matched GC and adjacent normal tissues, as well as in GC cell lines and immortalized human gastric epithelial cells. CCK8 assay, colony formation assay, and flow cytometry were used to assess the role of miR-874 in GC cell proliferation and apoptosis in vitro. Additionally, to determine the effects of miR-874 on GC cell proliferation and apoptosis in vivo, BALB/c nude mice were injected with GC cells transfected with a miR-874 mimic. The role of miR-874 in SPAG9 expression was assessed by luciferase assay, Western blotting, and RT-qPCR.Results: miR-874 was downregulated in GC cell lines and tissues. miR-874 overexpression in GC cells led to inhibition of cell proliferation and induction of apoptosis. Moreover, SPAG9 was identified as a direct miR-874 target, the expression of which was suppressed by miR-874. SPAG9 overexpression markedly promoted GC cell proliferation. Conclusions: miR-874 inhibited cell proliferation and induced apoptosis in GC cells. SPAG9 downregulation was crucial for the tumor-suppressive effects of miR-874. Hence, the miR-874/SPAG9 axis could serve as a novel therapeutic target in GC.

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“…Ki-67 positivity was defined as the presence of tan granules in the nucleus, and the percentage of positive cells was calculated 20 . The E-cadherin (E-cad) staining rate ≤ 50% was defined as the low expression group, and the staining rate > 50% was defined as the high expression group 21 . The absence of any of the four major mismatch repair (MMR) proteins, MLH1, MSH2, MSH6 and PMS2, was defined as positive mismatch repair function deficit (dMMR), and all positive proteins were defined as complete mismatch repair function (pMMR), namely, dMMR negative 22 .…”

Section: Methodsmentioning

confidence: 99%

A nomogram for predicting lymph node metastasis in early gastric signet ring cell carcinoma

You,

Chen,

Wang

2023

Sci Rep

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At present, the risk factors for lymph node metastasis in early gastric signet ring cell carcinoma (SRCC) remain unclear. However, it is worth noting that the LNM rate and prognosis of early gastric SRCC are superior to those of other undifferentiated cancers. With advancements in endoscopic technology, the 5-year survival rate following endoscopic treatment of early gastric cancer is comparable to traditional surgery while offering a better quality of life. The objective of this study was to develop a nomogram that can predict lymph node status in early gastric SRCC before surgery, aiding clinicians in selecting the optimal treatment strategy. A research cohort was established by retrospectively collecting data from 183 patients with early gastric SRCC who underwent radical gastrectomy with lymph node dissection at our hospital between January 2014 and June 2022. The predictors of early gastric signet ring cell carcinoma lymph node metastasis were identified in the study cohort using the least absolute selection and shrinkage operator (Lasso) and multivariate regression analysis, and a nomogram was developed. The discrimination, accuracy, and clinical practicability of the nomogram were assessed using receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis. The incidence of lymph node metastasis was 21.9% (40/183) overall. Multivariate logistic regression analysis revealed that tumor size and lymphovascular invasion (LVI) were independent risk factors for lymph node metastasis. Lasso regression analysis demonstrated that tumor size, invasion depth, LVI, E-cadherin expression, dMMR, CA242, NLR, and macroscopic type were associated with lymph node metastasis. The integrated discrimination improvement (IDI) (P = 0.034) and net reclassification index (NRI) (P = 0.023) were significantly improved when dMMR was added to model 1. In addition, the area under curve (AUC) (P = 0.010), IDI (P = 0.001) and NRI (P < 0.001) of the model were significantly improved when type_1 was included. Therefore, we finally included tumor size, invasion depth, dMMR, and macroscopic type to establish a nomogram, which had good discrimination (AUC = 0.757, 95% CI 0.687–0.828) and calibration. Decision curve analysis showed that the nomogram had good clinical performance. We have developed a risk prediction model for early gastric signet ring cell carcinoma that accurately predicts lymph node involvement, providing clinicians with a valuable tool to aid in patient counseling and treatment decision-making.

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The role of E-cadherin expression in the treatment of western undifferentiated early gastric cancer: Can a biological factor predict lymph node metastasis?

Cited by 10 publications

References 26 publications

The Expression of E-cadherin & HER2 in Gastric Carcinoma

The Expression of E-cadherin & HER2 in Gastric Carcinoma

miR-874 inhibits gastric cancer cell proliferation by targeting SPAG9

A nomogram for predicting lymph node metastasis in early gastric signet ring cell carcinoma

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