CD44+ cytokeratin-positive tumor cells in blood and bone marrow are associated with poor prognosis of patients with gastric cancer

Szczepanik, Antoni M.; Sierżęga, Marek; Drabik, Grażyna; Pituch‐Noworolska, Anna; Kołodziejczyk, Piotr; Zembala, Marek

doi:10.1007/s10120-018-0858-2

Cited by 33 publications

(21 citation statements)

References 33 publications

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“…In human GC, the mechanism responsible for maintaining malignant stem cells in the tumor microenvironment is largely unknown [47][48][49][50]. Among the stem cell populations in the stomach, the cells that may be targeted and transformed into tumor initiation cells during chronic Helicobacter pylori infection are those labeled by receptors on the surface of differentiated cluster 44 (CD44) cells [51].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer

Yang¹

2020

Med Oncol

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Gastric cancer (GC) is one of the most common malignant tumors in the world, and it is also the third largest cause of cancerrelated death in the world. As far as we know, no biomarker has been widely accepted for early diagnosis and prognosis prediction of gastric cancer. The purpose of this study is to find potential biomarkers to predict the prognosis of GC. The gene expression profiles of GSE2685 were downloaded from GEO database. Morpheus was used to calculate the differentially expressed genes (DEGs) between primary advanced gastric cancer tissues and noncancerous gastric tissues. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein-protein interaction (PPI) network of DEGs was constructed. Kaplan-Meier Plotter was used to determine the overall survival (OS) outcomes of UC5AC, MUC1, KRT7, GAPDH, CD44, and GEPIA was used to determine the Pearson correlation analysis. In total, 710 DEGs were identified in GC, including 396 upregulated genes and 314 downregulated genes. GO enrichment revealed that they were mainly enriched in binding, catalytic activity, cellular process and cell. KEGG pathway revealed that they were mainly enriched in metabolic pathways, pathways in cancer and PI3K-Akt signaling pathway. MUC5AC, MUC1, KRT7, GAPDH, CD44 were identified from the PPI network. MUC5AC, MUC1, KRT7, GAPDH, CD44 were demonstrated to have prognostic value for patients with GC. MUC5AC, MUC1 exhibited low expression levels in GC tissues, KRT7, GAPDH, CD44 presented high expression levels in GC tissues. In particular, KRT7 is hardly expressed in normal gastric tissues. MUC5AC and MUC1 were negatively correlated with GAPDH, CD44, respectively; and GAPDH was positively correlated with CD44 and KRT7, respectively. Moreover. MUC5AC, MUC1, KRT7, GAPDH, and CD44 are not only related to GC but also to apoptosis pathway. Results from the present study suggested that MUC5AC, MUC1, KRT7, GAPDH, CD44 may represent novel prognostic biomarkers for GC.

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Section: Discussionmentioning

confidence: 99%

Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer

Yang¹

2020

Med Oncol

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“…However, CD44 epithelial isoform has been found to be negatively correlated with lymphatic invasion and metastasis of colorectal cancer based on the statistical analysis of a total of 494 colorectal tumor samples [34]. Besides, numerous studies suggest that CD44 can be a promising predictor for clinical outcomes among cancer population, including gastric cancer [45,46], colorectal cancer [34], neuroblastoma [31], myxofibrosarcoma [47], glioma [21], endometrial cancer [40] and osteosarcoma [48]. According to survival analysis, grade II/III glioma patients with high mRNA expression of CD44 experienced poor overall survival (OS) and progression-free survival (PFS) in comparison with low mRNA level of CD44 in an independent manner [21].…”

Section: Open Accessmentioning

confidence: 99%

CD44 as a tumor biomarker and therapeutic target

et al. 2020

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CD44, a complex transmembrane glycoprotein, exists in multiple molecular forms, including the standard isoform CD44s and CD44 variant isoforms. CD44 participates in multiple physiological processes, and aberrant expression and dysregulation of CD44 contribute to tumor initiation and progression. CD44 represents a common biomarker of cancer stem cells, and promotes epithelial-mesenchymal transition. CD44 is involved in the regulation of diverse vital signaling pathways that modulate cancer proliferation, invasion, metastasis and therapy-resistance, and it is also modulated by a variety of molecules in cancer cells. In addition, CD44 can serve as an adverse prognostic marker among cancer population. The pleiotropic roles of CD44 in carcinoma potentially offering new molecular target for therapeutic intervention. Preclinical and clinical trials for evaluating the pharmacokinetics, efficacy and drug-related toxicity of CD44 monoclonal antibody have been carried out among tumors with CD44 expression. In this review, we focus on current data relevant to CD44, and outline CD44 structure, the regulation of CD44, functional properties of CD44 in carcinogenesis and cancer progression as well as the potential CD44-targeting therapy for cancer management.

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“…It has been shown that TEVs carrying MMPs may remodel ECM [described in detail in [ 74 , 75 , 76 ] by downregulating E-cadherin expression, degrading ECM components, and upregulating MMP-9, which, all together, facilitated tumor dissemination [ 69 ]. Others observed that TEVs-delivered HA induced motility of CD44 + CAFs and cancer cells [reviewed in [ 77 ], and that CD44 + tumor cells present in the blood [ 77 , 78 , 79 ] exhibited characteristics of cancer stem cells. Expression of this receptor on these cells might results in their dissemination into niches (organotropism) that might be possibly prepared by HA-coated TEVs (see below).…”

Section: Emt and The Role Of Cd44 And Tevsmentioning

confidence: 99%

CD44 and Tumor-Derived Extracellular Vesicles (TEVs). Possible Gateway to Cancer Metastasis

Szatanek

Baj‐Krzyworzeka

2021

IJMS

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Cancer metastasis, the final stage of tumor progression, is a complex process governed by the interplay of multiple types of cells and the tumor microenvironment. One of the aspects of this interplay involves the release of various factors by the tumor cells alone or by forcing other cells to do so. As a consequence of these actions, tumor cells are prepared in favorable conditions for their dissemination and spread to other sites/organs, which guarantees their escape from immunosurveillance and further progression. Tumor-derived extracellular vesicles (TEVs) represent a heterogeneous population of membrane-bound vesicles that are being actively released by different tumors. The array of proteins (i.e., receptors, cytokines, chemokines, etc.) and nucleic acids (i.e., mRNA, miR, etc.) that TEVs can transfer to other cells is often considered beneficial for the tumor’s survival and proliferation. One of the proteins that is associated with many different tumors as well as their TEVs is a cluster of differentiation 44 in its standard (CD44s) and variant (CD44v) form. This review covers the present information regarding the TEVs-mediated CD44s/CD44v transfer/interaction in the context of cancer metastasis. The content and the impact of the transferred cargo by this type of TEVs also are discussed with regards to tumor cell dissemination.

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CD44+ cytokeratin-positive tumor cells in blood and bone marrow are associated with poor prognosis of patients with gastric cancer

Cited by 33 publications

References 33 publications

Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer

Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer

CD44 as a tumor biomarker and therapeutic target

CD44 and Tumor-Derived Extracellular Vesicles (TEVs). Possible Gateway to Cancer Metastasis

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