Letter to the editor: For the core set of the bile lipidome and meta‐proteome signature, repeatability is the key
Authors: Shi‐Tao Jiang, Lei Zhang, Yi‐Yao Xu, Xin Lu
Journal: Hepatology (2022)

To the editor, We followed with interest the report by Sharma et al. on the identification of gallbladder carcinoma (GBC)–specific lipid species and microbial peptides using multi‐omics analysis.[1] As far as we know, there were few lipidomic studies using bile as the primary material in GBC. Sharma et al. showed us a relatively complete paradigm for bile lipidomics research. We really appreciated that their findings shed light on GBC diagnosis and pathogenesis. However, after reading this article, we would like to highlight some important issues about lipidomics in this study. Firstly, the authors performed an exploratory untargeted analysis of the samples with ultra‐high‐pressure liquid chromatography coupled with high‐resolution mass spectrometry technology. Comprehensive approaches using untargeted lipidomics could provide greater coverage of the lipidome but could sometimes result in ambiguous identifications. Because this method could generate a large amount of data containing unknown compounds, accurate quantification of each compound was not possible. Additionally, due to the complex composition of samples, matrix effects could have a significant impact on quantitative results.[2] Although the researchers added internal and external standards in the analytical process, they did not disclose the evaluation results. We thought this part should be clarified. Secondly, we observed that the authors only reported the age and gender of the enrolled patients, without information on whether the patients had metabolic syndrome, diabetes, hyperthyroidism, hypothyroidism, hepatitis, etc. They also did not describe whether the patients had used hormone drugs or lipid‐lowering medications. All these factors might affect the metabolic status of patients, thereby threatening the reproducibility of their findings.[3] We thought the authors should also disclose the timing of blood sample collection in the validation cohort. If the blood sample was not taken at the same time as the bile sample, the validation results might be unreliable. Thirdly, we noted that the authors did not report clinical staging for patients with GBC. There might be significant differences in bile composition for patients at different stages. Therefore, we believed that staging information should not be ignored and deserved further investigations. Furthermore, if the study included patients with advanced‐stage GBC, it would lead to an overestimation of sensitivity and specificity. In conclusion, although lipidomic approaches had provided profound evidence for altered metabolic pathways in GBC, we noted that few reported biomarkers had been validated and used in clinical practice. In addition to differences in lipid identification and quantification methods, heterogeneous populations were regarded as one of the major obstacles to the successful clinical application of this technology. FUNDING INFORMATION Supported by the CAMS Innovation Fund for Medical Sciences (2020‐I2M‐CT‐B‐026). CONFLICT OF INTEREST Nothing to report.