Patients with advanced head and neck squamous cell carcinoma (HNSCC) have a poor prognosis with the currently available therapy, and tumor recurrence is frequently observed. The discovery of specific membrane-associated cancer stem cell (CSC) markers is crucial for the development of novel therapeutic strategies to target these CSCs. To address this issue, we established sphere cultures to enrich CSCs and used them for plasma membrane proteomics to identify specific membrane signatures of the HNSCC spheres. Of a dataset that included a total of 376 identified proteins, 200 were bona fide membrane proteins. Among them, 123 proteins were at least 1.5-fold up- or down-regulated in the spheres relative to the adherent cultures. These proteins included cell adhesion molecules, receptors, and transporter proteins. Some of them play key roles in wnt, integrin, and TGF? signaling pathways. When we compared our dataset with two published hESC membrane protein signatures, we found 18 proteins common to all three of the databases. CD166 and CD44 were two such proteins. Interestingly, the expression of CD166, rather than that of the well-established HNSCC CSC marker CD44, was significantly related to the malignant behavior of HNSCC. Relative to CD166(low) HNSCC cells, CD166(high) HNSCC cells had a greater sphere-formation ability in vitro and tumor formation ability in vivo. Patients whose tumors expressed high levels of CD166 had a significantly poorer clinical outcome than those whose tumors expressed low levels of CD166 (cohort 1: 96 cases, p = 0.040), whereas the level of CD44 expression had only a marginal influence on the clinical outcome of patients with HNSCC (p = 0.078). The level of CD166 expression in HNSCC tumors was also associated with the tumor recurrence rate (cohort 2: 104 cases, p = 0.016). This study demonstrates that CD166 is a valuable cell surface marker for the enrichment of HNSCC stem cells and that plasma membrane proteomics is a promising biological tool for investigating the membrane proteins of CSCs.
Cyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy.
The carcinogenesis mechanism of adenoid cystic carcinoma (ACC) of the salivary gland is poorly understood. MicroRNA155 (miRNA155) has been involved in the carcinogenesis of many malignant tumors. The present study aims to examine the role of miRNA155 in tumor growth and invasion of ACC.
Oral squamous papilloma and papillary squamous cell carcinoma are 2 clinicopathologically distinctive papillary epithelial tumors. The current study aims to compare the clinical and pathologic features of these oral papillary lesions in a patient population from eastern China. A retrospective review in a series of patients with clinical and pathologic diagnosis of oral squamous papilloma (n = 141) and papillary squamous cell carcinoma (n = 56) was conducted. The average age of oral squamous papilloma was 51.0 years (male-to-female ratio, 1.82), with the palate being the predominant site. The average age of oral papillary squamous cell carcinoma was 63.3 years (male-to-female ratio, 1.67), with the gingiva being the predominant site. Multivariate analysis revealed that the elderly patient with papillary lesion (?60 years) was associated with 3.09-fold (95% confidence interval, 1.59-6.03) increased carcinoma risk compared with the nonelderly patient. The lesion located on the gingiva was associated with 4.98-fold (95% confidence interval, 1.96-12.63) increased carcinoma risk compared with other oral sites. Collectively, clinicopathologic features of oral squamous papilloma and papillary squamous cell carcinoma in eastern China were elucidated. Elderly patients with oral papillary lesions located on the gingiva correlate with higher carcinoma risk. It highlights the importance of using a histologic examination to confirm the clinical diagnosis for any suspicious papillary lesions.
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