Clinical Association of CD44 Expression with Proliferative Activity and Apoptotic State in Egyptian Patients Suffering from Ulcerative Colitis and Colorectal Carcinoma

El-Emshaty, Hoda; Hassan, Doaa K.; El-Hemaly, Mohamed; Ismail, Hisham

doi:10.31557/apjcp.2021.22.11.3577

Cited by 2 publications

(2 citation statements)

References 31 publications

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“…Cells with CD44 overexpression appear to have less spontaneous apoptosis and are more resistant to drug-induced cell death, inducing an anti-apoptotic effect. High expression of CD44 confers a selective advantage to resist apoptosis, thereby promoting cell transformation into a malignant phenotype in conjunction with other anti-apoptotic factors [41][42][43][44].…”

Section: Discussionmentioning

confidence: 99%

New Horizons in Metastatic Colorectal Cancer: Prognostic Role of CD44 Expression

Ziranu

Aimola

Pretta

et al. 2023

Cancers

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Background: The transmembrane glycoprotein CD44, the major hyaluronan (HA) receptor, has been proven to regulate cell growth, survival, differentiation, and migration. It is therefore widely considered to be involved in carcinogenesis. Its role as a new therapeutic target in solid tumors is under evaluation in clinical trials. The prognostic value remains controversial. Here, we aimed to investigate the correlation between CD44 expression and the clinicopathological features and survival in metastatic colorectal cancer (mCRC) patients. Methods: Data from 65 mCRC patients of the Medical Oncology Unit, University Hospital and University of Cagliari were retrospectively collected from 2008 to 2021. Immunohistochemical analysis was performed at the Pathology Division, University Hospital of Cagliari on 3 μm thick sections obtained from paraffin blocks. The intensity of immunohistochemical staining was subclassified into four groups: score 0 if negative or weak membrane staining in less than 10% of tumor cells; score 1+ if weak membrane staining in at least 10% of tumor cells or moderate membrane staining in less than 10% of tumor cells; score 2+ if moderate membrane staining in at least 10% of tumor cells or intensive membrane staining in less than 10% of tumor cells; score 3+ if intense membrane staining in at least 10% of tumor cells. Based on this score, we distinguished patients into low CD44 expression (score 0, 1+, 2+) and high CD44 expression (score 3+). Statistical analysis was performed with MedCalc (survival distribution: Kaplan–Meier; survival comparison: log-rank test; association between categorical variables: Fisher’s exact test). Results: Patients’ median age was 66 years (range 49–85). Regarding CD44 expression, score was 0 in 18 patients, 1+ in 15 patients, 2+ in 18 patients, and 3+ in 14 patients. Median overall survival (mOS) was 28.1 months (95%CI: 21.3–101). CD44 overexpression (3+) was correlated with poor prognosis (p = 0.0011; HR = 0.2), with a mOS of 14.5 months (95%CI 11.7 to 35.9) versus 30.7 months (95%CI 27.8 to 101) in lower CD44 expression. Higher CD44 expression was associated with clinically poor prognostic features: age ≥ 70 years (p = 0.0166); inoperable disease (p = 0.0008); stage IV at diagnosis (p = 0.0241); BRAF mutated (p = 0.0111), high-grade tumor (p = 0.0084). Conclusions: CD44 markedly correlated with aggressive tumor behavior and contributed to the earlier progression of disease, thus suggesting its role as a novel prognostic marker and potential therapeutic target for mCRC patients.

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Section: Discussionmentioning

confidence: 99%

New Horizons in Metastatic Colorectal Cancer: Prognostic Role of CD44 Expression

Ziranu

Aimola

Pretta

et al. 2023

Cancers

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“…CD44 not only is involved in the pathogenesis of UC [56] but also can serve as a predictor of tumor development and a therapeutic target [58]. Hypoxia leads to the activation of the hypoxia-inducible factor (HIF)-signaling pathway during inflammatory diseases [59].…”

Section: Discussionmentioning

confidence: 99%

Reconstruction and Differential Expression Profiling Core Target Analyses of the circRNA-miRNA-mRNA Network Based on Competitive Endogenous RNAs in Ulcerative Colitis

Chen

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Ulcerative colitis (UC) is a common autoimmune disease worldwide. Circular RNA (circRNA) is a type of noncoding ribonucleic acids (ncRNAs). In addition to their roles in numerous biological processes, circRNAs are also linked to a vast range of diseases including UC. Although previous studies have examined many circRNAs, the physiological and pathological roles of the circRNA-associated competing endogenous RNA (ceRNA) network in UC remain unclear. Thus, we constructed a circRNA-miRNA-mRNA network based on the ceRNA hypothesis by analyzing data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) database. Genes with higher degree values than others in the ceRNA network were selected as central nodes when constructing the corresponding core subnetworks. To fully understand the biological function of the ceRNA network, we entered all differentially expressed mRNAs (DEmRNAs) from the ceRNA network into the Database for Annotation and Integrated Discovery (DAVID), which was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We further entered DEmRNAs into the STRING database for protein-protein interaction (PPI) network analysis. The results elucidated that the ceRNA network comprised 403 circRNA nodes, 5 miRNA nodes, 138 mRNA nodes, and 559 edges. Three core ceRNA subnetworks centered on hsa-miR-342-3p, hsa-miR-199a-5p, and hsa-miR-142-3p were reconstructed in this study. GO and KEGG enrichment analyses identified 167 enriched GO categories and 14 enriched KEGG pathway terms. The core PPI network was composed of 15 core targets, of which CD44, HIF1A, and MMP2 were the most significant. In summary, 3 hub miRNAs (hsa-miR-342-3p, hsa-miR-199a-5p, hsa-miR-142-3p) and 3 hub genes (CD44, HIF1A, and MMP2) might play an important role in the development of UC. These hub nodes, first proposed here, might also be used as potential diagnostic markers and therapeutic targets.

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Clinical Association of CD44 Expression with Proliferative Activity and Apoptotic State in Egyptian Patients Suffering from Ulcerative Colitis and Colorectal Carcinoma

Cited by 2 publications

References 31 publications

New Horizons in Metastatic Colorectal Cancer: Prognostic Role of CD44 Expression

New Horizons in Metastatic Colorectal Cancer: Prognostic Role of CD44 Expression

Reconstruction and Differential Expression Profiling Core Target Analyses of the circRNA-miRNA-mRNA Network Based on Competitive Endogenous RNAs in Ulcerative Colitis

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