[Lung cancer under stress]

Area of Science:

• Cellular Biology
• Oncology
• Biochemistry

Background:

• Autophagy is crucial for cellular homeostasis and survival under stress, with therapeutic potential.
• Assessing autophagy in formalin-fixed, paraffin-embedded (FFPE) tissues is challenging but vital for clinical translation.
• Standardized analysis of autophagy markers in FFPE tissues can aid in discovering predictive biomarkers for cancer.

Purpose of the Study:

• To establish reliable immunohistochemical visualization of autophagy markers in FFPE lung cancer tissue.
• To evaluate the prognostic impact of autophagy-related markers, specifically LC3 and p62, in lung cancer patients.
• To explore the potential of autophagy markers as predictive biomarkers in lung cancer.

Main Methods:

• Developed and validated immunohistochemistry (IHC) for visualizing autophagy proteins (LC3, p62) in FFPE tissues.
• Utilized lung cancer cell lines with modified autophagy states for marker validation.
• Correlated IHC findings with quantitative protein expression via Western blot in cell lines and FFPE tumor samples.
• Assessed the prognostic significance of LC3 and p62 expression in stage I/II non-small cell lung cancer (NSCLC) and pulmonary squamous cell carcinoma cohorts.

Main Results:

• Successfully visualized autophagy-related proteins LC3 and p62 in FFPE tissues using IHC, with dot-like staining representing autophagic vesicles.
• Demonstrated significant correlation between IHC staining and quantitative protein expression via Western blot.
• Found no clear prognostic value for dot-like LC3 and p62 co-expression in stage I/II NSCLC or pulmonary squamous cell carcinomas.
• Identified p62 expression as an independent prognostic factor for shorter survival in both lung cancer cohorts.

Conclusions:

• Validated a reliable method for visualizing autophagy markers (LC3, p62) in FFPE lung cancer tissues.
• Autophagy status, based on LC3-p62 co-expression, did not show a clear prognostic role in the studied lung cancer cohorts.
• Highlighted the autophagy-independent prognostic role of p62 in lung cancer, warranting further investigation.
• Suggested further research into p62's interactions with other stress factors and autophagy's role during cancer treatment.