Title: High aldehyde dehydrogenase levels are detectable in the serum of patients with lung cancer and may be exploited as screening biomarker

Biography:

Dr. Alessandra Rossi earned her M.Sc in biology, with specialism in molecular biology, at the Department of Pharmacology at the University of Bologna. There, she performed her PhD thesis at the Department of Human Pathology studying the molecular mechanisms of retinoic acid derivatives in cancer models. After earning her specialization in pharmacology, she worked as a postdoctoral scientist at the University of Siena and Temple University (Philadelphia, PA, USA), where she had the opportunity to apply her research skills in several projects that included the screening and profiling of anti-cancer compounds and the elucidation of new anti-cancer properties of molecules already in the clinic. After having worked for two years in the medical affairs at the pharmaceutical company Eli Lilly, she joined the University Medical Center Eppendorf of Hamburg, where she focused on the development of targeted Next Generation Sequencing approaches for mutational profiling of plasma cell dyscrasias and analysis of liquid biopsy in solid tumors. Currently, she is in the scientific committee of Luigi and Teresa de Beaumont Bonelli Foundation for Cancer Research, is working as a nutritionist for cancer patients and as a researcher at the University of Bologna, where she has been working on the evaluation of potential screening biomarkers for lung cancer.

Abstract

Since early detection improves overall survival in lung cancer, identification of screening biomarkers for patients at risk represents an area of intense investigation. Tumor liberated protein (TLP) has been previously described as a tumor-associated antigen (complex) present in the sera from lung cancer patients. Here, we set out to identify the nature of TLP to develop this as a potential biomarker for lung cancer screening. Materials and Methods: Beginning from the peptide epitope RTNKEASI previously identified from TLP complex, we produced a rabbit anti-RTNKEASI serum and evaluated it in the lung cancer cell line A549 by means of immunoblot and peptide completion assay (PCA). The TLP sequence identification was conducted by mass spectrometry. The detected protein was, then, analyzed in patients with non small cell lung cancer (NSCLC), benign lung pathologies and healthy donors, by ELISA. Results: The anti-RTNKEASI antiserum detected and immunoprecipitated a 55kDa protein band in the lysate of A549 cells identified as aldehyde dehydrogenase isoform 1A1, revealing the molecular nature of at least one component of the previously described TLP complex. Next, we screened blood samples from a non-tumor cohort of 26 patients and 45 NSCLC patients with different disease stages for the presence of ALDH1A1 and global ALDH. This analysis indicated that serum positivity was highly restricted to patients with NSCLC (ALDH p<0.001; ALDH1A1 p=0.028). Interestingly, the global ALDH test resulted positive in more NSCLC samples compared to the ALDH1A1 test, suggesting that other ALDH isoforms might add to the sensitivity of the assay. Conclusion: Our data indicate that ALDH levels are elevated in the sera of NSCLC patients, even with early stage disease, and may thus be evaluated as part of a marker panel for non-invasive detection of NSCLC.