Reacquisition of E-cadherin expression in metastatic deposits of signet-ring cell carcinoma of the upper gastrointestinal system: a potential anchor for metastatic deposition

Yihong, R.; Siegal, Gene P.; Wei, Shi

doi:10.1136/jclinpath-2016-203959

Cited by 3 publications

(4 citation statements)

References 34 publications

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“…Thus, it is not appropriate for us to add other features to the grouping. These deficiencies may have partially influenced the results, as evidenced by the fact that CDH1 ( 46 ) and CDS1 expression did not differ between two groups. Moreover, since the number of SRCs in the TCGA database is too small, it is difficult to conduct grouping for subsequent analysis of genes of interest.…”

Section: Discussionmentioning

confidence: 99%

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

Meng

Zhou

et al. 2022

Front. Surg.

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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.

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Section: Discussionmentioning

confidence: 99%

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

Meng

Zhou

et al. 2022

Front. Surg.

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“…MUC4, mucin 4; ERBB2, human epidermal growth factor-like receptor 2; ERBB3, human epidermal growth factor-like receptor 3; PI3K, phosphatidylinositol 3-kinase; p38 MAP, p38 mitogen-activated protein kinases; RAC1, Rac family small GTPase 1. Created with BioRender.com in primary SRCC supports its role during epithelial-mesenchymal transition (EMT) in tumor development and metastasis; however, its re-expression benefits tumor cells to form solid metastatic deposits [31]. Moreover, heterozygous germline CDH1 mutations intensify the risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC).…”

Section: Genetic Factors Involved In Srcc Of Stomach and Gejmentioning

confidence: 99%

“…The loss of E-cadherin was a recurrent event in SRCC of several organs, and this was more prominent in SRCC than in non-SRCC of similar tumors [ 30 ]. The reduced E-cadherin in primary SRCC supports its role during epithelial-mesenchymal transition (EMT) in tumor development and metastasis; however, its re-expression benefits tumor cells to form solid metastatic deposits [ 31 ]. Moreover, heterozygous germline CDH1 mutations intensify the risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC).…”

Section: Molecular Alterationsmentioning

confidence: 99%

Signet ring cell cancer of stomach and gastro-esophageal junction: molecular alterations, stage-stratified treatment approaches, and future challenges

Kumar

Jose

Usman

et al. 2021

Langenbecks Arch Surg

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Purpose 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. Methods 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. Results 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. Conclusion 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.

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“…E-cadherin and ARID1A expression was semiquantitatively scored on a scale of 0 (no staining), 1 + (weak), 2 + (moderate) to 3 + (strong; equivalent to normal epithelium or stromal cells of the stomach). A score of 2 + or less was regarded as loss or reduction [11,12]. MLH1 or MSH2 was considered to be a loss or reduction of nuclear reactivity together with a positive background reaction in non-neoplastic epithelial or stromal cells.…”

Section: Evaluation Of Positive Casesmentioning

confidence: 99%

Histological diversity and molecular characteristics in gastric cancer: relation of cancer stem cell-related molecules and receptor tyrosine kinase molecules to mixed histological type and more histological patterns

et al. 2020

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Background Gastric cancers (GCs) are still one of the leading causes of cancer-related mortality. The histological and molecular features of GC may differ widely from area to area within the same tumor. Intratumoral heterogeneity has been considered a major obstacle to an efficient diagnosis and successful molecular treatment. Methods We selected and reevaluated 842 GC cases and analyzed the relationship between numbers or composites of histological patterns within tumors, and clinicopathological parameters in mucosal and invasive areas. In addition, we searched for the GC-associated molecules or molecular subtypes marking histological diversities. Results GC cases with more histological numbers or mixed types in invasive areas showed significantly higher T grade and staging, whereas those in mucosal areas did not show any significant associations. GCs with histological diversities showed poorer prognosis and characteristically expressed cancer stem cell-related molecules (CD44, CD133 or ALDH1) and receptor tyrosine kinase molecules (HER2, EGFR or c-MET) as well as Helicobacter pylori infection. Expressions of CD44, HER2, c-MET, laminin 5•2 or retained E-cadherin in mucosal areas were predictive of more histological numbers and mixed types in invasive areas. In addition, the chromosomal instability subtype of GC showed significant associations with more histological numbers and mixed histological type, whereas the genomic stability subtype of GC showed a significant relationship with pure type. Conclusions We displayed the relationship between histological diversity and molecular features in GC, and we hope that the present data can contribute to the early diagnosis and prevention, and effective treatment of GC.

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Reacquisition of E-cadherin expression in metastatic deposits of signet-ring cell carcinoma of the upper gastrointestinal system: a potential anchor for metastatic deposition

Cited by 3 publications

References 34 publications

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

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

Signet ring cell cancer of stomach and gastro-esophageal junction: molecular alterations, stage-stratified treatment approaches, and future challenges

Histological diversity and molecular characteristics in gastric cancer: relation of cancer stem cell-related molecules and receptor tyrosine kinase molecules to mixed histological type and more histological patterns

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