Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease

Abstract

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.

Keywords: chronic obstructive pulmonary disease; inductively coupled plasma; lung cancer; mass spectrometry; metallomics; metals.

Figure 1

Impact of LC and COPD on the human serum metallomic profile. (A) Heatmap showing the serum elemental profiles of the different groups under study (p < 0.05) (adjusted by FDR correction). (B) Principal component analysis (PCA). (C) Scatter plot of partial least squares-discriminant analysis (PLS−DA). Classification of HC, LC, COPD and COPD-LC groups based on their elemental profile of human serum. (D) Scatter plot of partial least squares-discriminant analysis (PLS-DA). Classifications of HC, LC, COPD of varying severity (COPD−mi, COPD−mo, COPD−s, and COPD−vs), and COPD−LC groups based on their serum elemental profiles. (E) Box plots of levels determined for the most significantly altered elements in the serum samples of the groups under study.

Figure 2

ROC curves showing significant differences between elements in the (A) LC, (B) COPD-mo, (C) COPD-s, and (D) COPD-LC groups compared with those in the HC group (AUC values higher than 0.75).

Figure 3

Spearman correlation heatmap showing correlations between metals in the (a) HC, (b) LC, (c) COPD, and (d) COPD-LC groups. * significant (p < 0.05) and strong (rho > 0.5) correlations.