Similar Source of Differential Blood mRNAs in Lung Cancer and Pulmonary Inflammatory Diseases: Calls for Improved Strategy for Identifying Cancer-Specific Biomarkers

Background: Many studies try to identify cancer diagnostic biomarkers by comparing peripheral whole blood (PWB) of cancer samples and healthy controls, explicitly or implicitly assuming that such biomarkers are potential candidate biomarkers for distinguishing cancer from nonmalignant inflammation-associated diseases. Methods: Multiple PWB gene expression profiles for lung cancer/inflammation-associated pulmonary diseases were used for differential mRNAs identification and comparison and for proportion estimation of PWB cell subtypes. Results: The differentially expressed genes (DE genes) between lung cancer/inflammation-associated pulmonary patients and healthy controls were reproducibly identified in different datasets. For these DE genes observed in lung cancer/ inflammation-associated pulmonary diseases, more than 90.2% were differentially expressed between myeloid cells and lymphoid cells, with at least 96.8% having consistent directions of regulation (up- or down-regulations) in myeloid cells compared to lymphoid cells, explainable by the shifted populations of PWB cell subtypes under the disease conditions. The comparison of DE genes for lung cancer and inflammation-associated pulmonary diseases showed that the overlapping genes were 100% consistent in the sense of direction of regulation. Conclusions: The differential blood mRNAs observed in lung cancer and in inflammation-associated pulmonary diseases were similar, both mainly reflecting the difference between myeloid cells and lymphoid cells predominantly determined by PWB cell population shifts. Thus, the strategy of comparing cancer with healthy controls may provide little information of the ability of the identified candidate biomarkers in discriminating cancer from inflammation-associated pulmonary diseases.