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Tumor-Dependent and -Independent Serum/Plasma Biomarkers for Early Diagnosis of Lung Cancer

Alexander Lu and Lijuan Zhang*

Lung cancer continually leads in mortality among cancer patients in the world. In order to reduce the lung cancer mortalities, early treatment is required but early diagnosis is still farfetched because the hopeful serum/plasma biomarkers identified so far lack sufficient sensitivity, specificity, and reproducibility even for diagnosis of lung cancer at late stage. During the past decades, the realization that the genetic mutations are not the only blame and the abnormal lung tissue instigated by aging, cigarette smoking, and environmental toxins plant the “soil” for lung cancer. Such discovery leads to the successful development of novel anti-cancer drugs that target the “soil” by either inhibiting angiogenesis process required for cancer cells to expand or by empowering the immune cells to kill the cancer cells in tumor. Based on the literature search, there have been no reports using the same concept to identify the “soil”- dependent cancer biomarkers. However, in recent years, the “OMICS” technologies including genomics, epigenomics, proteomics, glycomics, lipidomics, and metabolomics have been used to compare the molecular differences between the serum/plasma samples from normal and cancer patients systematically and generated large amounts of data. By reviewing the published data, we picked and discussed 12 lung cancer biomarkers and proposed them to be tumordependent and tumor-independent biomarkers released by liver, immune cells, or other organs/tissues. The existence of tumor-independent biomarkers indicates that the “lung cancer soil” is planted beyond the lung. Furthermore, the biomarkers can be proteins/peptides, DNA, RNA, glycans, lipids, metabolites, or any combinations of them.