A Panel of Bile Volatile Organic Compounds Servers as a Potential Diagnostic Biomarker for Gallbladder Cancer

Abstract

As no reliable diagnostic methods are available, gallbladder cancer (GBC) is often diagnosed until advanced stages, resulting in a poor prognosis. In the present study, we assessed whether volatile organic compounds (VOCs) could be used as a diagnostic tool for GBC. The VOCs in bile samples collected from 32 GBC patients were detected by gas chromatography-ion mobility spectrometry (GC-IMS), and 54 patients with benign gallbladder diseases (BGD) were used as controls. Both principal component analysis and unsupervised hierarchical clustering analysis gave a clear separation of GBC and BGD based on the bile VOC data collected from GC-IMS. A total of 12 differentially expressed VOCs were identified, including four upregulated (cyclohexanone, 2-ethyl-1-hexanol, acetophenone, and methyl benzoate) and eight downregulated [methyl acetate, (E)-hept-2-enal, hexanal, (E)-2-hexenal, (E)-2-pentenal, pentan-1-ol, 1-octen-3-one, and (E)-2-octenal] in GBC compared with BGD. ROC analysis demonstrated a 12-VOC panel con-structed by four machine learning algorithms, which was superior to the traditional tumor marker, CA19-9. Among them, support vector machines and linear discriminant analysis provided the highest AUCs of 0.972, with a sensitivity of 100% and a specificity of 94.4% in the diagnosis of GBC. Collectively, VOCs might be used as a potential tool for the diagnosis of GBC.

Identification of urinary volatile organic compounds as a potential non-invasive biomarker for esophageal cancer

“…Similar to our previous studies, substances were characterized by the retention index of the molecule and the drift time of its ions before being quantified by the intensity of the signal peaks 24 . Therefore, for each sample to be measured, three-dimensional data (retention index, drift time, peak strength) was obtained (Fig.…”

“…Similarly, studies investigating diagnostic models based on VOCs detected in exhaled breath have been reported in lung cancer 23 . VOCs in bile and other samples have further been demonstrated to be useful for the diagnosis of tumors 24 .…”

A Systematic Review and Meta-Analysis: Volatile Organic Compound Analysis in the Detection of Hepatobiliary and Pancreatic Cancers

“…This is further supported by a previous study, reporting higher concentration of intramural bacteria in pancreatic cancer patients who had biliary obstructions and subsequently biliary decompression [ 70 ]. An added advantage over other matrices is that the bile VOC concentration is less affected by external factors [ 43 ]. For the aforementioned reasons, bile-based VOCs showed the highest performance indices in our subgroup analysis.…”

“… Forest plot illustrating the performance of volatile organic compounds for the detection of hepatobiliary and pancreatic cancer [ 30 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. …”

“…The following supporting information can be downloaded at: , Figure S1: Funnel plot assessing the publication bias; Figure S2: Forest plot illustrating the performance of breath based volatile organic compounds for the detection of hepatobiliary and pancreatic cancer; Figure S3: Forest plot illustrating the performance of urine based volatile organic compounds for the detection of hepatobiliary and pancreatic cancer; Figure S4: Forest plot illustrating the performance of blood based volatile organic compounds for the detection of hepatobiliary and pancreatic cancer; Figure S5: Forest plot illustrating the performance of bile based volatile organic compounds for the detection of hepatobiliary and pancreatic cancer; Table S1: Risk of bias assessment using QUADAS-2 tool; Table S2: Regression coefficient and its p values by meta-regression analysis (fixed-effect model) for covariates sample media, analytical methods and cancer type. References [ 30 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ] are cited in the supplementary materials…”