Prognostic value of E-Cadherin and its tumor suppressor role in Saudi women with advanced epithelial ovarian cancer

Assidi, Mourad; Jafri, Mohammad Alam; Abu‐Elmagd, Muhammad; Pushparaj, Peter Natesan; Saddick, Salina; Messaoudi, Safia; Alkhatabi, Heba; Al‐Maghrabi, Jaudah; Anfinan, Nisreen; Sait, Maram; Omri, Abdelfatteh El; Sait, Hesham; Basalamah, Hussain; Buhmeida, Abdelbaset; Sait, Khalid

doi:10.1080/19932820.2021.1994741

Cited by 3 publications

(6 citation statements)

References 41 publications

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“…In fact, several reports have shown that when epithelial tumor cells switch from expressing E-CAD to expressing N-CAD (cadherin switch phenomenon), they acquire the ability to activate Fibroblast Growth Factor Receptor (FGFR) pathways. Our results together with our previous study about E-Cad expression in the same cohort confirmed the cadherin switch ( 32 ). In fact, while the E-CAD expression was decreasing at the advanced stages (starting from the EMT and marked by cancer invasion and migration), the N-CAD expression was increasing; and both markers were prognosticators of poor survival outcomes ( 32 ).…”

Section: Discussionsupporting

confidence: 91%

“…Our results together with our previous study about E-Cad expression in the same cohort confirmed the cadherin switch ( 32 ). In fact, while the E-CAD expression was decreasing at the advanced stages (starting from the EMT and marked by cancer invasion and migration), the N-CAD expression was increasing; and both markers were prognosticators of poor survival outcomes ( 32 ). In fact, once N-CAD is overexpressed, it has been shown to affect tumor cell polarity and behavior through its direct interaction with the FGFR, which regulates cancer cell motility and invasion ( 55 , 56 ).…”

Section: Discussionsupporting

confidence: 91%

“…Subsequently, all H&E stained slides from all blocks were reviewed by a pathologist to select the tumour areas to be punched/cored. The details of TMA construction mapping, and validation have been described elsewhere ( 32 , 33 ).…”

Section: Methodsmentioning

confidence: 99%

“…The concentrated N-CAD rabbit polyclonal antibody (catalog # ab66025, Abcam, dilution: 1:20) was used. The detailed protocol of the IHC procedure was performed as described elsewhere ( 32 , 34 ). Briefly, the automated Ventana began the run by deparaffinizing the paraffin-embedded tissue sections with EZ Prep™.…”

Section: Methodsmentioning

confidence: 99%

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High N-Cadherin Protein Expression in Ovarian Cancer Predicts Poor Survival and Triggers Cell Invasion

Assidi

2022

Front. Oncol.

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Ovarian cancer (OC) is among the most lethal cancer among all gynaecological malignancies. Since most OC patients are diagnosed only at advanced stages mainly because of their imperceptible/nonspecific symptoms, survival rates are low. Therefore, more molecular biomarkers are needed to achieve more effective molecular stratification for better prognostic and theranostic outcomes. The cadherin family, particularly N-cadherin (N-CAD; also known as CDH2), is critical for cell-cell adhesion and epithelial- mesenchymal transition (EMT) of cancer. N-CAD protein has also been shown to be overexpressed in many advanced carcinomas. The aim of this study was to investigate the expression patterns of N-CAD protein, determine their correlations with the clinicopathological features of OC patients, and evaluate its prognostic value and involvement in EMT and metastasis. Protein expression of N-CAD was studied in 117 formalin-fixed and paraffin-embedded (FFPE) blocks from patients diagnosed with OC using Tissue Microarray and immunohistochemistry techniques. The N-CAD protein was overexpressed in 58% of our OC cohort. Furthermore, its cytoplasmic overexpression was significantly correlated with tumor grade (p= 0.05), tumor subtype (p= 0.05), tumor necrosis (p= 0.01), and age at menarche (p= 0.002). Interestingly, Kaplan-Meier analysis showed a significant correlation of disease-free survival (DFS) with OC patients with cytoplasmic N-CAD overexpression (p< 0.03, log rank). Patients with high N-CAD expression have approximately twice the recurrence rate at 5-year follow-up. The results of this study demonstrate a poor prognostic role of N-CAD overexpression in OC, which is reflected in higher recurrence and death rates of OC and its molecular contribution to EMT and distant metastasis. Therefore, OC patients with overexpressed N-CAD need to be monitored more frequently and closely. Further studies with larger patient cohorts are needed to validate these findings, demystify the role of N-CAD in OC pathophysiology, and further investigate its role as a potential therapeutic target.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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High N-Cadherin Protein Expression in Ovarian Cancer Predicts Poor Survival and Triggers Cell Invasion

Assidi

2022

Front. Oncol.

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“…To verify the expression level of the six intersection genes in metastatic and non-metastatic osteosarcoma, we compared the expression level of these six genes in U2OS and 143-B osteosarcoma cell lines, which represent the low metastatic and high metastatic osteosarcoma, respectively ( 30 ). Loss expression of E-cad was reported to associate with cancer metastasis, and VIM was reported to promote migration of cancer cells ( 31 , 32 ). To confirm the migration and metastatic ability of U2OS and 143-B cells, we quantified the E-cad and VIM expression in these two cell lines.…”

Section: Resultsmentioning

confidence: 99%

PKIB involved in the metastasis and survival of osteosarcoma

Wan

Gu²,

Liu³

et al. 2022

Front. Oncol.

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Osteosarcoma is frequently metastasized at the time of diagnosis in patients. However, the underlying mechanism of osteosarcoma metastasis remains poorly understood. In this study, we evaluated DNA methylation profiles combined with gene expression profiles of 21 patients with metastatic osteosarcoma and 64 patients with non-metastatic osteosarcoma from TARGET database and identified PKIB and AIM2 as hub genes related to the metastasis of osteosarcoma. To verify the effects of PKIB on migration and invasion of osteosarcoma, we performed wound-healing assay and transwell assay. The results showed that PKIB significantly inhibited the migration and invasion of osteosarcoma cells, and the Western blot experiments showed that the protein level of E-cad was upregulated and of VIM was downregulated in 143-B cell recombinant expression PKIB. These results indicate that PKIB inhibit the metastasis of osteosarcoma. CCK-8 assay results showed that PKIB promote the proliferation of osteosarcoma. In addition, the Western blot results showed that the phosphorylation level of Akt was upregulated in 143-B cells overexpressing PKIB, indicating that PKIB promotes the proliferation of osteosarcoma probably through signaling pathway that Akt involved in. These results give us clues that PKIB was a potential target for osteosarcoma therapy. Furthermore, combined clinical profiles analysis showed that the expression of AIM2- and PKIB- related risk scores was significantly related to the overall survival of patients with osteosarcoma. Thus, we constructed a nomogram based on AIM2 and PKIB expression–related risk scores for osteosarcoma prognostic assessment to predict the 1-, 2-, 3-, and 5-year overall survival rate of patients with metastatic osteosarcoma, assisting clinicians in the diagnosis and treatment of metastatic osteosarcoma.

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Strong prognostic value of SLAMF7 protein expression in patients with lymph node‑positive breast cancer

Assidi

2022

Oncol Lett

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Breast cancer (BC) in women is the second most commonly diagnosed type of cancer worldwide, and the leading cause of cancer-related mortality among women. To date, surgery is the main treatment option, often combined with other (neo)adjuvant therapeutic modalities to treat this malignancy and prevent relapse. Despite the invasive aspects of the majority of these therapeutic interventions and their associated side-effects, these treatments are still unable to effectively cure this disease and prevent relapse. Thus, there is an urgent need for the identification of more relevant biomarkers for more effective theranostics. Signaling lymphocytic activation molecule F7 (SLAMF7) is a glycosylated cell surface protein that plays a critical role in immune cell functions under both healthy conditions and in cancer. It is specifically targeted by elotuzumab for the treatment of multiple myeloma. The present retrospective study aimed to investigate the expression patterns of SLAMF7 and evaluate its associations with clinicopathological features, including the survival outcomes of patients with BC. The protein expression of SLAMF7 in BC was investigated in 278 lymph node-positive formalin-fixed and paraffin-embedded (FFPE) tissue blocks using tissue microarray and immunohistochemistry techniques. The results revealed a significant association between cytoplasmic SLAMF7 protein expression and several clinicopathological parameters, particularly age at diagnosis (P<0.007), tumor invasion (P<0.008) and vascular invasion (P= 0.05). Kaplan-Meier analysis revealed that the overexpression of SLAMF7 was a strong positive prognosticator of both disease-free and disease-specific survival in the patients with BC (log-rank P= 0.001 and P= 0.008, respectively). This suggests that patients with SLAMF7 protein expression have a higher survival rate and a lower recurrence rate. On the whole, the present study demonstrated that a weak or no SLAMF7 expression was a powerful prognosticator of poor survival outcomes associated with both tumor and vascular invasion. Therefore, elotuzumab (as SLAMF7monoclonal antibody therapy) may be a promising option for targeted therapy worthy of clinical testing in patients with BC.

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Prognostic value of E-Cadherin and its tumor suppressor role in Saudi women with advanced epithelial ovarian cancer

Cited by 3 publications

References 41 publications

High N-Cadherin Protein Expression in Ovarian Cancer Predicts Poor Survival and Triggers Cell Invasion

High N-Cadherin Protein Expression in Ovarian Cancer Predicts Poor Survival and Triggers Cell Invasion

PKIB involved in the metastasis and survival of osteosarcoma

Strong prognostic value of SLAMF7 protein expression in patients with lymph node‑positive breast cancer

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