Plasma metabolomics study in screening and differential diagnosis of multiple primary lung cancer

Abstract

Background: Multiple primary lung cancer (MPLC) is becoming increasingly common in clinical practice. Imaging examination is sometimes difficult to differentiate from intrapulmonary metastasis (IM) or single primary lung cancer (SPLC) before surgery. There is a lack of effective blood biomarkers as an auxiliary diagnostic method. Participants and Methods A total of 179 patients who were hospitalized and operated in our department from January to June 2019 were collected, and they were divided into SPLC with 136 patients, MPLC with 24 patients, and IM with 19 patients. In total, 96 healthy people without lung cancer were enrolled. Medical history, imaging, and pathology data were assembled from all participants. Plasma metabolomics analysis was performed by quadrupole time-of-flight tandem mass spectrometry, and data were analyzed using SPSS19.0/Simca 14.1/MetaboAnalyst5.0 software. Significant metabolites were selected by variable importance in projection, P value, and fold change. The area under the receiver operating characteristic curve was used to evaluate their diagnostic ability. Results There were significant differences in plasma metabolite profiles between IM and MPLC. Seven metabolites were screened out. Two metabolites had higher levels in IM, and five metabolites had higher levels in MPLC. All had favorable discriminating capacity. Phosphatidyl ethanolamine (38:5) showed the highest sensitivity (0.95) and specificity (0.92). It was followed by l-histidine with sensitivity 0.92 and specificity 0.84. l-tyrosine can be used to identify SPLC and MPLC. The panel composed of related metabolites exhibited higher diagnostic ability. Eight principal metabolites caused remarkable differences between healthy people and MPLC, and five of them had area under the curves greater than 0.85, showing good discriminating power. Conclusion Through the study of plasma metabolomics, it was found that there were obvious differences in the metabolite profiles of MPLC, IM, SPLC, and the healthy population. Some discovered metabolites possessed excellent diagnostic competence with high sensitivity and specificity. They had the potential to act as biomarkers for the screening and differential diagnosis of MPLCs.

Comment on ‘Plasma metabolomics study in screening and differential diagnosis of multiple primary lung cancer’

“…Specifically, we are concerned about the potential impact of differences in pathological stage and tumor grade between groups, which were not accounted for in the study. As shown in 1 , there were significant differences in pathological stage ( P =0.027) and tumor grade ( P =0.014) between the groups. Therefore, the differences observed in plasma metabolomics may have been caused by differences in these variables rather than the group differences between MPLC, intrapulmonary metastasis (IM), and synchronous primary lung cancer (SPLC).…”

“…Secondly, the conclusions drawn in this study 1 may be flawed due to confounding variables that were not properly addressed. Specifically, we are concerned about the potential impact of differences in pathological stage and tumor grade between groups, which were not accounted for in the study.…”

“…We read with great interest the study titled ‘ Plasma metabolomics study in screening and differential diagnosis of multiple primary lung cancer ’ 1 . The study investigates the potential of plasma metabolomics as a tool for screening and diagnosing multiple primary lung cancer (MPLC).…”

“…As we all know, the use of a control group is essential in medical studies to provide a comparison group that is not affected by the variable under investigation. In this study 1 , the control group consisted of patients who underwent thoracic surgery but were found to be healthy after the surgery. However, this study did not provide sufficient information about the underlying diseases of the control group, which could potentially affect the study’s conclusions.…”

A commentary on “plasma metabolomics study in screening and differential diagnosis of multiple primary lung cancer”

“…Liu et al 4 conducted an original research to screen out metabolites with diagnostic significance as potential biomarkers for MPLC, by comparing different plasma samples from MPLC, intrapulmonary metastasis, single primary lung cancer, and healthy people. They found that there were obvious differences in the metabolite profiles among them.…”