High Aldehyde Dehydrogenase Levels Are Detectable in the Serum of Patients with Lung Cancer and May Be Exploited as Screening Biomarkers.

Alessandra Rossi,Giulio Tarro,Gerhard Schön,Mascha Binder,Hans Klose,Minna Voigtlaender,Carsten Bokemeyer,Hartmut Schlüter,Moreno Paolini,Sonja Loges,Martin Reck

doi:10.1155/2019/8970645

Abstract

Objectives 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 the 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) and benign lung pathologies and healthy donors, by ELISA. Results The anti-RTNKEASI antiserum detected and immunoprecipitated a 55 kDa 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.

Highlights

Despite various treatment approaches such as surgery, radiotherapy, and chemotherapy, lung cancer remains the most common cancer-related cause of death in the world with a 15% 5-year survival rate of about [1,2,3]
We show that aldehyde dehydrogenase (ALDH) isoforms other than 1A1 may be released into the blood of Non-small cell lung cancer (NSCLC) patients, and screening sensitivity may be even more improved by employing an isoform-unspecific global ALDH assay without apparently lowering specificity
A partial extinction of the 55 kDa protein band in the presence of the blocking RTNKEASI peptide compared to the control peptide confirmed that the 55 kDa band was recognized by RTNKEASIdirected antibodies from the antiserum (Figure 1(c))

Summary

Introduction

Despite various treatment approaches such as surgery, radiotherapy, and chemotherapy, lung cancer remains the most common cancer-related cause of death in the world with a 15% 5-year survival rate of about [1,2,3]. Numerous studies investigated mainly the potential effects of chest X-rays and low-dose helical computed tomography (CT) for imaging alongside with sputum cytology on lung cancer detection. These studies showed encouraging results about stage distribution in favor of earlier stage disease, better surgical resection of the tumors, and an increased survival rate, an improvement on overall mortality could not be determined [7,8,9,10,11,12,13,14,15,16]. Serological markers such as Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and Cyfra 21-1 are serological markers used for the monitoring of treatment response in lung cancer patients, but their application as screening biomarkers is still a challenging question [17,18,19]

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Conclusion