Prognostic significance of p62/SQSTM1 subcellular localization and LC3B in oral squamous cell carcinoma.

Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE

Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.

Adaptor Proteins, Signal Transducing/*metabolism ; Carcinoma, Squamous Cell/*metabolism ; Microtubule-Associated Proteins/*metabolism ; Mouth Neoplasms/*metabolism; Adult ; Autophagy/physiology ; Biomarkers, Tumor/metabolism ; Carcinoma, Squamous Cell/pathology ; Cell Nucleus/metabolism ; Cell Survival ; Cytoplasm/metabolism ; Female ; Humans ; Hyperplasia/metabolism ; Hyperplasia/pathology ; Male ; Middle Aged ; Mouth Mucosa/metabolism ; Mouth Mucosa/pathology ; Mouth Neoplasms/pathology ; Prognosis ; Retrospective Studies ; Sequestosome-1 Protein ; Survival Rate

Background: Autophagy is a programmed cell survival mechanism that has a key role in both physiologic and pathologic conditions. The relationship between autophagy and cancer is complex because autophagy can act as either a tumour suppressor or as a tumour promoter. The role of autophagy in oral squamous cell carcinoma (OSCC) is controversial. Several studies have claimed that either a high or low expression of autophagy-related proteins was associated with poor prognosis of OSCCs. The aims of the study were to compare autophagy in OSCCs, verrucous hyperplasias, and normal oral mucosas, and to inspect the prognostic role of autophagy in OSCCs.
Methods: We used the autophagosome marker, LC3B, and autophagy flux marker, p62/SQSTM1 (p62), by using immunohistochemistry, and examined p62 mRNA by RNA in situ hybridization, to evaluate autophagy in 195 OSCCs, 47 verrucous hyperplasias, and 37 normal oral mucosas. The prognostic roles of LC3B and p62 protein expressions in OSCCs were investigated.
Results: We discovered that the normal oral mucosa exhibited limited LC3B punctae and weak cytoplasmic p62 staining, whereas the OSCCs exhibited a marked increase in LC3B punctae and cytoplasmic p62 expression. The expression pattern of LC3B and cytoplasmic p62 of the verrucous hyperplasias were between normal oral mucosas and OSCCs. The normal oral mucosas, verrucous hyperplasias, and OSCCs presented no differences in nuclear p62 expression and the p62 mRNA level. p62 mRNA expression was elevated in a minority of cases. High p62 mRNA expression was associated with high p62 protein expression in the cytoplasm. Increased LC3B punctae, high cytoplasmic p62, and low nuclear p62 expressions in OSCCs were associated with aggressive clinicopathologic features and unfavourable prognosis. In addition, low nuclear p62 expression was an independent prognostic factor for overall and disease-specific survival rates. Furthermore, we disclosed that high cytoplasmic p62 expression accompanied with either a low or high LC3B expression, which indicated autophagy impairment under basal or activated autophagic activity, was associated with aggressive behaviour in advanced OSCCs.
Conclusions: We suggested that autophagy was altered during cancer initiation and progression. Autophagy impairment contributed to cancer progression in advanced OSCCs.

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0 (Adaptor Proteins, Signal Transducing)
0 (Biomarkers, Tumor)
0 (MAP1LC3B protein, human)
0 (Microtubule-Associated Proteins)
0 (SQSTM1 protein, human)
0 (Sequestosome-1 Protein)

Date Created: 20140702 Date Completed: 20141017 Latest Revision: 20220330

20231215

PMC4150268

10.1038/bjc.2014.355

24983366