Abstract
Autophagy is involved in maintaining cellular homeostasis under stress conditions. It also plays an important role in various diseases including cancer. Pulmonary squamous cell carcinomas (pSQCC) at present lack targetable molecular alterations, and demand alternative therapeutic options. We assessed the expression levels of autophagy related proteins LC3B, p62, and HMGB1 in 271 primary resected pSQCC by immunohistochemistry, in correlation with clinical and pathological parameters, as a rationale for a potential autophagy directed therapy. LC3B, p62, and HMGB1 staining showed various patterns. LC3Bhighp62low levels, suggested to indicate intact activated autophagy, were associated with prolonged disease specific survival (DSS) and LC3Bhighp62high levels, indicating activated but late stage impaired autophagy, with shorter DSS (p = 0.024). p62high expression regardless of LC3B, however, showed an even stronger association with shorter DSS (p = 0.015) and was also an independent negative prognostic factor in multivariate analysis (HR = 2.99; 95% CI 1.38–6.52; p = 0.006). HMGB1 expression correlated neither with the expression of LC3B and p62, nor with patients’ outcome. Different states of autophagy characterized by distinct p62 and LC3B expression patterns may be linked to patient’s prognosis in pSQCC. Our results, however, point also to an autophagy independent role of p62 with an even more pronounced prognostic impact compared to autophagy related p62.
Highlights
Non-small cell lung cancer (NSCLC), the largest subgroup of pulmonary carcinomas, belongs in the category of the most frequent malignant diseases worldwide [1]
Following a preliminary study on early-stage NSCLC comprising both adenocarcinomas and pulmonary squamous cell carcinomas (pSQCC) [21] we investigated the relevance of light chain 3 B (LC3B), p62/sequestosome 1 (SQSTM1), and high-mobility group protein-B1 (HMGB1) expression in a well-characterized cohort of pSQCCs [22] as a potential rationale for autophagy directed therapy in pSQCC
Cancer Control and American Joint Committee on Cancer [23]; HR, hazard ratio. In this tissue-based study, we examined the impact of the expression of autophagy-related proteins LC3B, p62, and HMGB1 in a consecutive cohort of squamous cell carcinomas of the lung
Summary
Non-small cell lung cancer (NSCLC), the largest subgroup of pulmonary carcinomas, belongs in the category of the most frequent malignant diseases worldwide [1]. Adenocarcinomas harbor alterations allowing a more detailed tumor classification according to their mutational status, which represents targets for treatment. Antitumoral therapy targeting specific molecular alterations is unavailable in pulmonary squamous cell carcinomas (pSQCC) [2], some genotypic characteristics present potential. Autophagosomes are structures with double layer membranes that engulf organelles and cellular components for subsequent degradation and represent the functional and structural hallmark of autophagy. Proteins that play a role in the formation of autophagosomes have been discussed to harbor the potential to visualize autophagy in tissue samples [13,14]. The stress-associated protein, high-mobility group protein-B1 (HMGB1), that partially serves as a regulator of autophagy has been described as harboring a prognostic impact in cancer, in particular in association with LC3B [16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
