<scp>CD</scp>44 and <scp>ALDH</scp>1 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma

Ortiz, Rafael Carneiro; Lopes, NP; Amôr, Nádia Ghinelli; Ponce, José; Schmerling, Cláudia Kliemann; Lara, Vanessa Soares; Moysés, Raquel Ajub; Rodini, Camila Oliveira

doi:10.1111/jop.12734

Cited by 31 publications

(35 citation statements)

References 25 publications

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“…ALDH1 and other proteins from the ALDH family belong to the most prevalent markers to identify CSC in HNSCC [34]. ALDH1 expression was linked to treatment resistance, CSC-like properties, higher circulating myeloid-derived suppressor cells, and poor prognosis as well as angiolympathic invasion in oral cavity SCC [49,50]. Although in the literature high ALDH1 expression was mostly correlated to worse prognosis [51,52], the authors could not show an effect on survival in their surgical cohort.…”

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confidence: 94%

Role of cancer stem cell markers ALDH1, BCL11B, BMI-1, and CD44 in the prognosis of advanced HNSCC

et al. 2020

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Purpose Cancer stem cells (CSCs) are held accountable for the progress of head and neck squamous cell carcinoma (HNSCC). In the presented study, the authors evaluated the prognostic value of CSC markers in two particular HNSCC cohorts. Methods This two cohort study consisted of 85 patients with advanced stage HNSCC, treated with primary radio(chemo)therapy (pRCT), and 95 patients with HNSCC, treated with surgery and partially adjuvant radio(chemo)therapy. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were assessed. Samples were assessed for the expression of different molecular stem cell markers (ALDH1, BCL11B, BMI-1, and CD44). Results In the pRCT cohort, none of the baseline patient and tumor features exhibited a statistically significant relation with survival in either the cohort or the human papillomavirus (HPV)-stratified subcohorts. High expression of BMI-1 significantly decreased OS and DFS, while high expression of CD44 decreased all modes of survival. Multivariate analysis showed significant prognostic influence for all tested CSC markers, with high BMI-1 and CD44 decreasing survival (BMI-1: OS, DFS, DSS; CD44: OS, DFS) and high ALDH1 and BCL11B showing a beneficial effect on survival (ALDH1: OS, DFS; BCL11B: OS, DSS). In the surgical cohort, classical prognosticators such as HPV status, R1 resection, and nodal status in HPV-negative HNSCC played a significant role, but the tested CSC markers showed no significant effect on prognosis. Conclusion Although validation in independent cohorts is still needed, testing for CSC markers in patients with advanced or late stage HNSCC might be beneficial, especially if many comorbidities exist or disease is irresectable. The findings might guide the development and earlier use of targeted therapies in the future.

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confidence: 94%

Role of cancer stem cell markers ALDH1, BCL11B, BMI-1, and CD44 in the prognosis of advanced HNSCC

et al. 2020

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“…Oral squamous cell carcinoma is a highly aggressive malignant tumor that is often associated with cervical lymph node metastasis . Tumor metastasis and invasion have been linked to abnormal DNA damage repair . MDC1 is a DNA damage response mediator protein, which forms a complex with DNA topoisomerase 2‐binding protein 1 (TOPBP1) to maintain chromosome stability when DNA double‐strand breaks occur during mitosis .…”

Section: Discussionmentioning

confidence: 99%

Effect of silencing of mediator of DNA damage checkpoint protein 1 on the growth of oral squamous cell carcinoma in vitro and in vivo

Zhang

Liu

et al. 2019

European J Oral Sciences

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Effect of silencing of mediator of DNA damage checkpoint protein 1 on the growth of oral squamous cell carcinoma in vitro and in vivo. Eur J Oral Sci 2019; 127: 494-499. © 2019 Eur J Oral SciMediator of DNA damage checkpoint protein 1 (MDC1) is involved in DNA damage repair and has been linked to tumor invasion, metastasis, and prognosis. This study investigated the effects of MDC1 in oral squamous cell carcinoma (OSCC) in vitro and in vivo. RNA interference-mediated knockdown of MDC1 was performed in two OSCC cell lines (Tca-8113 and KB). Real-time PCR and western blotting were performed to determine expression of mRNA and protein, respectively, of MDC1. Cell viability was assessed using the MTT assay. Colony-formation assays were performed by staining with 0.5% crystal violet. Cell migration and invasion were detected by Transwell assays. The role of MDC1 in OSCC was examined in vivo via injection of Tca-8113 cells transfected with MDC1 small interfering (si)RNA or negative-control siRNA into a mouse xenograft model of OSCC. Our results showed that MDC1 knockdown decreased cell proliferation. Inhibition of MDC1 decreased colony formation of Tca-8113 and KB cells by 62% and 68%, respectively, and MDC1 knockdown reduced the number of migratory and invasive cells compared with the control group. Moreover, the xenograft mouse model of MDC1 knockdown showed reduced tumor growth. Our study suggests that MDC1 plays a role in tumorigenesis and might be a potential target for the treatment of patients with OSCC. Material and methods Cell cultureThe OSCC cell lines Tca-8113 and KB were obtained from the Shanghai Cell Bank of the Chinese Academy of Sciences (Shanghai, China). Both cell lines were authenticated by short tandem repeat analysis and were mycoplasma-free. Tca-8113 and KB cells were inoculated into RPMI-1640 (Gibco, Invitrogen, Paisley, UK) containing

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“…[25][26][27][28][29][30][31] CSCs in oral cancer demonstrate elevated expression levels of stem cell markers, such as Oct-4, SOX2, Nanog, Nestin, CK19, B-cellspecific Moloney murine leukaemia virus integration site 1 (Bmi-1), CD117 (c-kit), CD44 and CD133, and decreased expression levels of involucrin and CK-13. 25,26,[32][33][34] Evidence supporting this stems from the finding that the signalling pathways regulating normal stem cell division (i.e., Notch, Wnt, Hedgehog and Bmi-1) are involved in oral cancer development. 27,30,31,35,36 Recent evidence indicates that CSCs within surgical margins play a crucial role in the clinical outcomes of cancer.…”

Section: Alterations In the Expression Pattern Of Om-scms In Osf Opmmentioning

confidence: 99%

Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation

Sharma¹,

Fonseca

Hunter

et al. 2020

Int J Oral Sci

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The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.

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CD44 and ALDH1 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma

Cited by 31 publications

References 25 publications

Role of cancer stem cell markers ALDH1, BCL11B, BMI-1, and CD44 in the prognosis of advanced HNSCC

Role of cancer stem cell markers ALDH1, BCL11B, BMI-1, and CD44 in the prognosis of advanced HNSCC

Effect of silencing of mediator of DNA damage checkpoint protein 1 on the growth of oral squamous cell carcinoma in vitro and in vivo

Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation

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