Abstract
BackgroundLung cancer remains the leading cause of mortality from malignant tumors, non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, and individualized diagnosis and treatment is an effective trend. The individual characteristics of different traditional Chinese medicine (TCM) syndromes of NSCLC patients may be revealed by highly specific molecular profiles.MethodsIn this study, 10 NSCLC patients with Qi deficiency and Yin deficiency (QDYD) syndrome and 10 patients with Qi deficiency of lung-spleen (QDLS) syndrome in TNM stage III-IV as well as 10 healthy volunteers were enrolled. Aiming at the varied syndromes of NSCLC patients with “Yin deficiency” as the main difference, a proteomics research based on data-independent acquisition (DIA) was developed. Of the dysregulated proteins in NSCLC patients, lipid metabolism was significantly enriched. Thereafter, nontargeted lipidomics research based on UPLC-Q-TOF/MS was performed in 16 patients, with 8 individuals randomly selected from each syndrome group. Furthermore, the considerably different characteristics between the syndromes and pathological mechanisms of NSCLC were screened by statistical and biological integrations of proteomics and lipidomics and the differential metabolic pathways of the two similar syndromes were further explored. Besides, lipids biomarkers were verified by a clinically used anticancer Chinese medicine, and the level of key differential proteins in the two syndromes was also validated using ELISA.ResultsThe results showed that glycerophospholipid metabolism, sphingolipid metabolism, glycolipid metabolism, and primary bile acid biosynthesis were altered in NSCLC patients and that glycerophospholipid metabolism was significantly changed between the two syndromes in lipidomics analysis. Among the proteins and lipids, ALDOC and lysophosphatidylcholine (LPCs) were revealed to have a strong relationship by statistical and biological integration analysis, and could effectively distinguish QDLS and QDYD syndromes. Notably, the patients with different syndromes had the most typical metabolic patterns in glycerophospholipid metabolism and glycolysis, reflecting the differences in the syndromes dominated by “Yin deficiency”.ConclusionsALDOC and LPCs could be employed for the differentiation of NSCLC patients with QDLS and QDYD syndromes, and “Yin deficiency” might be associated with glycerophospholipid metabolism and glycolysis pathway. The results provided a theoretical basis for “Syndrome differentiation” in TCM diagnosis. Moreover, the developed integrated strategy could also provide a reference for individualized diagnosis and treatment of other diseases.
Highlights
Lung cancer remains the leading cause of mortality from malignant tumors, non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, and individualized diagnosis and treatment is an effective trend
Dysregulated proteins in lung cancer patients and proteome differences between syndromes To explore the effect of Qi deficiency and Yin deficiency (QDYD) and Qi deficiency of lung-spleen (QDLS) NSCLC on human plasma proteomics, data-independent acquisition (DIA) technology was applied to collect protein data from patients and healthy subjects
For quality control of the proteomics analysis, the results suggested that the mass spectrometry performance was stable, the accuracy of mass spectrometry was perfect, and that the data was globally normalized to the median peptide signal, leading to reliable proteomics data. (Additional file 1: Figure S1)
Summary
Lung cancer remains the leading cause of mortality from malignant tumors, non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, and individualized diagnosis and treatment is an effective trend. The individual characteristics of different traditional Chinese medicine (TCM) syndromes of NSCLC patients may be revealed by highly specific molecular profiles. Traditional Chinese medicine (TCM) is a time-honored practice and is gaining in popularity in Asia, where it plays an important role in the treatment of lung cancer, as well as other countries in the West. Evidence on improving quality of life, prolonging survival time and reducing chemotherapy induced toxicity has demonstrated the effectiveness of TCM, especially for patients with advanced-stage lung cancer [2]. Through the description of TCM syndrome, the subjective feeling of patients as well as clinical manifestations of diseases can be reflected, and the essence of pathological changes at certain stages of a disease can be revealed [3]
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