Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer

• Published in: Oncotarget Vol. 7; no. 26; pp. 39544 - 39555
• Main Authors: Schläfli, Anna M, Adams, Olivia, Galván, José A, Gugger, Mathias, Savic, Spasenija, Bubendorf, Lukas, Schmid, Ralph A, Becker, Karl-Friedrich, Tschan, Mario P, Langer, Rupert, Berezowska, Sabina
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 28-06-2016
• Subjects: Aged; Autophagy; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - metabolism; Cell Nucleus - metabolism; Cytoplasm - metabolism; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lung Neoplasms - diagnosis; Lung Neoplasms - metabolism; Male; Microtubule-Associated Proteins - metabolism; Middle Aged; Multivariate Analysis; Prognosis; Research Paper; Retrospective Studies; RNA-Binding Proteins - metabolism; Tissue Array Analysis; Treatment Outcome; non-small cell lung cancer; p62/SQSTM1; autophagy; immunohistochemistry; LC3
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.9647

Autophagy is a cellular degrading process that promotes tumor cell survival or cell death in cancer, depending on the progress of oncogenesis. Protein light chain 3 (LC3) and p62/SQSTM1 (p62) are associated with autophagosomal membranes that engulf cytoplasmic content for subsequent degradation. We studied LC3 and p62 expression using immunohistochemistry in a large cohort of 466 stage I/II non-small cell lung cancer (NSCLC) using a tissue microarray. We evaluated dot-like cytoplasmic expression of LC3 and dot-like, cytoplasmic and nuclear staining for p62 in relation to clinico-pathological parameters.LC3 expression correlated with all p62 patterns, as those correlated among each other (p < 0.001 each). There was no correlation with stage, age or gender. A combination of high LC3/high p62 dot-like staining (suggesting impaired autophagy) showed a trend for better outcome (p = 0.11). Interestingly, a combined low cytoplasmic/low nuclear p62 expression regardless of dot-like staining was an independent prognostic factor for longer survival (p = 0.006; HR=1.96), in addition to tumor stage (p = 0.004; HR=1.4).The autophagy markers LC3 and p62 are differentially expressed in NSCLC, pointing towards a biologically significant role. High LC3 levels seem to be linked to lower tumor aggressiveness, while high general p62 expression was significantly associated with aggressive tumor behavior.