Abstract
Oral squamous cell carcinoma (OSCC) is one of the most common cancer types worldwide and can be divided into three major subsites: buccal mucosal SCC (BMSCC), tongue SCC (TSCC), and lip SCC (LSCC). The autophagy marker microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1(SQSTM1) are widely used proteins to evaluate autophagy in tumor tissues. However, the role of MAP1LC3B and SQSTM1 in OSCC is not fully understood, particularly in certain subsites. With a tissue microarray comprised of 498 OSCC patients, including 181 BMSCC, 244 TSCC, and 73 LSCC patients, we found that the expression levels of MAP1LC3B and cytoplasmic SQSTM1 were elevated in the tumor tissues of three subsites compared with those in adjacent normal tissues. MAP1LC3B was associated with a poor prognosis only in TSCC. SQSTM1 was associated with poor differentiation in three subsites, while the association with lymph node invasion was only observed in BMSCC. Interestingly, MAP1LC3B was positively correlated with SQSTM1 in the tumor tissues of BMSCC, whereas it showed no correlation with SQSTM1 in adjacent normal tissue. The coexpression of higher MAP1LC3B and SQSTM1 demonstrated a significantly worse disease-specific survival (DSS) and disease-free survival (DFS) in patients with BMSCC and LSCC, but not TSCC. The knockdown of MAP1LC3B and SQSTM1 reduced autophagy, cell proliferation, invasion and tumorspheres of BMSCC cells. Additionally, silencing both MAP1LC3B and SQSTM1 enhanced the cytotoxic effects of paclitaxel in the tumorspheres of BMSCC cells. Taken together, MAP1LC3B and SQSTM1 might modulate autophagy to facilitate tumorigenesis and chemoresistance in OSCC, particularly in BMSCC.
Highlights
Oral squamous cell carcinoma (OSCC), a type of head and neck cancer, is one of the most common malignant tumors worldwide [1,2]
We scored the total MAP1LC3B expression levels in all tissues and found that the MAP1LC3B levels were increased in tumor tissues compared with those in adjacent normal tissues in three major subsites of OSCC, including buccal mucosal SCC (BMSCC) (3.31 ± 1.44 vs. 2.30 ± 1.06, p < 0.001), tongue SCC (TSCC) (1.48 ± 1.02 vs. 0.59 ± 0.94, p < 0.001) and lip SCC (LSCC) (3.14 ± 1.43 vs. 2.32 ± 0.71, p < 0.001) (Table 1)
Similar to the results of MAP1LC3B, cytoplasmic SQSTM1 was elevated in three subsites of OSCC (BMSCC: 2.89 ± 1.11 vs. 1.89 ± 1.00, p < 0.001; TSCC: 2.78 ± 1.08 vs. 1.88 ± 0.77, p < 0.001; and LSCC: 3.22 ± 1.25 vs. 2.03 ± 0.64, p < 0.001) (Table 1)
Summary
Oral squamous cell carcinoma (OSCC), a type of head and neck cancer, is one of the most common malignant tumors worldwide [1,2]. Regarding the clinical association of autophagy markers, microtubule-associated light chain 3B (MAP1LC3B), an essential protein for autophagosome elongation, is associated with poor survival in various cancer types; some studies have indicated that cancer patients with high MAP1LC3B expression have a better outcome [12], in K-Ras-mutated colorectal cancer cells. High levels of cytoplasmic SQSTM1 have been found to be associated with poor survival in several cancer types [12]. We compared the MAP1LC3B and SQSTM1 protein levels in tumor tissues and adjacent normal tissues in three major subsites of OSCC, including BMSCC, TSCC and LSCC. Our results show that both MAP1LC3B and cytoplasmic SQSTM1 were elevated in tumor tissues in three subsites of OSCC compared with that in adjacent normal tissues. Our results suggest that MAP1LC3B and SQSTM1 could serve as biomarkers or therapeutic targets for BMSCC
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