Expression and associations of TRAF1, BMI-1, ALDH1, and Lin28B in oral squamous cell carcinoma

Abstract

Tumor necrosis factor receptor-associated factor 1, an adaptor protein of tumor necrosis factor 2, is involved in classical nuclear factor (NF)-κB activation and lymphocyte recruitment. However, less is known about the expression and association of tumor necrosis factor receptor-associated factor 1 with cancer stem cell markers in oral squamous cell carcinoma. This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor 1 and stem cell characteristic markers (lin28 homolog B, B cell-specific Moloney murine leukemia virus integration site 1, and aldehyde dehydrogenase 1) in oral squamous cell carcinoma and analyze their relations. Paraffin-embedded tissues of 78 oral squamous cell carcinomas, 39 normal oral mucosa, and 12 oral dysplasia tissues were employed in tissue microarrays, and the expression of tumor necrosis factor receptor-associated factor 1, B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B was measured by immunohistostaining and digital pathological analysis. The expression of tumor necrosis factor receptor-associated factor 1 was higher in the oral squamous cell carcinoma group as compared with the expression in the oral mucosa (p < 0.01) and oral dysplasia (p < 0.001) groups. In addition, the expression of tumor necrosis factor receptor-associated factor 1 was associated with those of B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B (p = 0.032, r 2 = 0.109; p < 0.0001, r 2 = 0.64; and p < 0.001, r 2 = 0.16) in oral squamous cell carcinoma. The patient survival rate was lower in the highly expressed tumor necrosis factor receptor-associated factor 1 group, although the difference was not significant. The clustering analysis showed that tumor necrosis factor receptor-associated factor 1 was most related to aldehyde dehydrogenase 1. These findings suggest that tumor necrosis factor receptor-associated factor 1 has potential direct/indirect regulations with the cancer stem cell markers in oral squamous cell carcinoma, which may help in further analysis of the cancer stem cell characteristics.

Prognostic Significance of ALDH1, Bmi1, and OCT4 Expression in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

“…Nevertheless, whether this explanation holds true in patients with OSCC needs to be explored. In the present study, Bmi1 expression did not affect the survival rate of OSCC cases, which was in accordance with other studies by Tamatani et al, 39 Jayasooriya et al, 30 and Wu et al 55 However, Hayry et al 56 found Bmi1 expression to favor better prognosis in tongue carcinoma in contrast to our results. This could be due to the varied pathogenesis involved in OSCC in accordance with different etiological factor and different epithelial types in the population groups.…”

“…A similar positive association between ALDHI1 and Bmi1 was also observed in oral and oesophageal carcinoma samples. 55 , 64 The HNSCC cell culture studies have noted that ALDH1-positive cells exhibited an increased Bmi1 expression and silencing of Bmi1 greatly reduced the tumorigenicity of the cells and made them more prone to radiotherapy. These results infer a relationship between ALDH and Bmi1.…”

Cancer Stem Cells in Oral Cavity Squamous Cell Carcinoma: A Review

“…Expression of TNF receptor-associated factor 1 has been found to be higher in OCSCC than normal oral mucosa and oral epithelial dysplasia, and is associated with reduced overall survival, Moloney murine leukemia virus integration site 1, Lin28 homolog B, and most importantly ALDH1 in OSCC (102). …”

TRAF1 Signaling in Human Health and Disease

“…In human skin, TRAF1 is expressed at higher levels, as measured by histology, in actinic keratosis as well as in squamous cell carcinoma, compared to normal skin (59, 60). Since UV exposure is thought to contribute to these conditions, Yamamoto et al tested the role of UV in induction of TRAF1 in mice.…”