CEACAM5 has different expression patterns in gastric non-neoplastic and neoplastic lesions and cytoplasmic staining is a marker for evaluation of tumor progression in gastric adenocarcinoma

Liu, Jia‐Ning; Wang, Hongbo; Zhou, Chengcheng; Hu, Sanyuan

doi:10.1016/j.prp.2014.06.024

Cited by 13 publications

(8 citation statements)

References 30 publications

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“…Among the downregulated genes we found ADAMTS1, a metalloprotease with anti-angiogenic activity expressed at low levels in primary tumors ( 82 ). Moreover, the 3 most overexpressed specific genes in diffuse gastric cancer resulted REG4, LCN2 and CEACAM5 (fold change of 16.97, 7.63 and 6.34 respectively): REG4 is generally overexpressed in gastric cancer and promotes peritoneal metastasis, increasing adhesion ability of gastric cancer cells ( 83 ); LCN2 is overexpressed in gastric cancer mucosa infected with H. pylori and correlated with invasion, metastasis and poor prognosis of gastric cancer ( 84 , 85 ); the expression of CEACAM5 is associated with tumor progression, invasion and migration and it is considered an independent prognostic predictor in patients with advanced stages of gastric cancer ( 86 , 87 ). Conversely the most downregulated gene in diffuse gastric cancer subset is REG1A (fold change of −7.47), a tumor suppressor that, when overexpressed, reduces invasion and promotes apoptosis of gastric cancer cells, and that is typically downregulated in gastric cancer patients ( 88 , 89 ).…”

Section: Resultsmentioning

confidence: 99%

Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

et al. 2021

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Gastric cancer is the fifth most common malignancy but the third leading cause of cancer-associated mortality worldwide. Therapy for gastric cancer remain largely suboptimal making the identification of novel therapeutic targets an urgent medical need. In the present study we have carried out a high-throughput sequencing of transcriptome expression in patients with gastric cancers. Twenty-four patients, among a series of 53, who underwent an attempt of curative surgery for gastric cancers in a single center, were enrolled. Patients were sub-grouped according to their histopathology into diffuse and intestinal types, and the transcriptome of the two subgroups assessed by RNAseq analysis and compared to the normal gastric mucosa. The results of this investigation demonstrated that the two histopathology phenotypes express two different patterns of gene expression. A total of 2,064 transcripts were differentially expressed between neoplastic and non-neoplastic tissues: 772 were specific for the intestinal type and 407 for the diffuse type. Only 885 transcripts were simultaneously differentially expressed by both tumors. The per pathway analysis demonstrated an enrichment of extracellular matrix and immune dysfunction in the intestinal type including CXCR2, CXCR1, FPR2, CARD14, EFNA2, AQ9, TRIP13, KLK11 and GHRL. At the univariate analysis reduced levels AQP9 was found to be a negative predictor of 4 years survival. In the diffuse type low levels CXCR2 and high levels of CARD14 mRNA were negative predictors of 4 years survival. In summary, we have identified a group of genes differentially regulated in the intestinal and diffuse histotypes of gastric cancers with AQP9, CARD14 and CXCR2 impacting on patients’ prognosis, although CXCR2 is the only factor independently impacting overall survival.

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Section: Resultsmentioning

confidence: 99%

Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

et al. 2021

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“…As a member of the broblast growth factors, FGF20 plays important roles in morphogenesis, angiogenesis, tissue remodeling, and carcinogenesis through the Wnt/β-catenin signaling pathway [28,29]. CEACAM5 may also promote tumor invasion and migration and may be a promising biomarker for GC in pre-diagnostic and prognostic evaluations [30,31]. Moreover, TP53INP2 is a key positive regulator of autophagy and may act as a novel autophagic adaptor through recruitment of ubiquitinated substrates to autophagosomes for degradation [32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

ZSCAN18 Promoter is Hypermethylated and Its Restored Expression Inhibits Proliferation in Gastric Cancer

Ren

et al. 2021

Preprint

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Background: Zinc finger and scan domain containing 18 (ZSCAN18) belongs to the zinc finger transcription factor superfamily, which consists of hundreds of members that play critical roles in all steps of tumorigenesis. Although hypermethylation of the ZSCAN18 promoter and its consequent deficiency in a variety of malignancies have been reported recently, its functions and mechanisms in the initiation and progression of gastric cancer (GC) are not clear. This study aims to investigate the roles of ZSCAN18 in gastric carcinogenesis.Methods: Methylation of ZSCAN18 promoter in GC cell lines was analyzed via MassARRAY and treatment with 5-aza-2′-deoxycytidine. Bioinformatics analysis, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry, Cell Counting Kit 8, colony formation, and an in vivo xenograft tumor model were used to examine the expression and function of ZSCAN18. Survival analysis was performed to determine the correlation between ZSCAN18 expression and the prognosis of patients with GC. Genes modulated by ZSCAN18 in NCI-N87 cells were identified through RNA next-generation sequencing and verified by qRT-PCR in AGS and NCI-N87 cells.Results: ZSCAN18 expression was markedly reduced in GC tissues compared with adjacent normal tissues as a result of hypermethylation in GC. Likewise, ZSCAN18 expression was significantly reduced in a panel of GC cell lines as a result of the densely methylated ZSCAN18 promoter. Forced expression of ZSCAN18 inhibited proliferation in AGS and NCI-N87 cells in vitro. Additionally, ZSCAN18 impaired the growth of NCI-N87 cells in immunodeficient mice. Survival analysis showed that ZSCAN18 expression was positively associated with favorable outcomes in patients with GC. RNA next-generation sequencing showed three representative genes (FGF20, CEACAM5, and TP53INP2) involved in downstream signaling pathways modulated by ZSCAN18.Conclusions: Collectively, this study unveils the anti-cancer role of ZSCAN18 in GC and provides a promising diagnostic and therapeutic target.

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“…However, results from the clinical trial on the first-generation CEACAM5-specific CAR T cells were disappointed with unfavorable "on-target, off-tumor" toxicity (Thistlethwaite et al, 2017). As Trop 2 is overexpressed in NEPC with limited nonoverlapping expressions with CEACAM5 in normal tissues, a "dual-gate" CAR-T is equipped with Trop 2 targeted CAR in addition to CEACAM5 targeted CAR is being explored to mitigate the toxicity (Hsu et al, 2020;Liu et al, 2014).…”

Section: Pf-06664178mentioning

confidence: 99%

Recent advances in trophoblast cell‐surface antigen 2 targeted therapy for solid tumors

Liao

Wang

Zeng

et al. 2021

Drug Development Research

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Trophoblast cell-surface antigen 2 (Trop 2) is a transmembrane glycoprotein that is highly expressed in various cancer types with relatively low or no baseline expression in most normal tissues. Its overexpression is associated with tumor growth and poor prognosis; Trop 2 is, therefore, an ideal therapeutic target for epithelial cancers. Several Trop 2 targeted therapeutics have recently been developed for the treatment of cancers, such as anti-Trop 2 antibodies and antibody-drug conjugates (ADCs), as well as Trop 2-specific cell therapy. In particular, the safety and clinical benefit of Trop 2-based ADCs have been demonstrated in clinical trials across multiple tumor types, including those with limited treatment options, such as triple-negative breast cancer, platinum-resistant urothelial cancer, and heavily pretreated non-small cell lung cancer. In this review, we elaborate on recent advances in Trop 2 targeted modalities and provide an overview of novel insights for future developments in this field.

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CEACAM5 has different expression patterns in gastric non-neoplastic and neoplastic lesions and cytoplasmic staining is a marker for evaluation of tumor progression in gastric adenocarcinoma

Cited by 13 publications

References 30 publications

Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

ZSCAN18 Promoter is Hypermethylated and Its Restored Expression Inhibits Proliferation in Gastric Cancer

Recent advances in trophoblast cell‐surface antigen 2 targeted therapy for solid tumors

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