Proteomic profiling of human sera for discovery of potential biomarkers to monitor abstinence from alcohol abuse

Abstract

Although numerous biomarkers or biomarker candidates have been discovered to detect levels of drinking and intervals of time after last drinking episode, only a few biomarkers have been applied to monitor abstinence in a longer interval (≥6 wks) from alcohol abuse. Considering sample sources, sensitivity, and specificity, new biomarkers from blood with better accuracy are needed. To address this, serum proteomic profiles were compared between pre- and post- treatment samples from subjects seeking treatment for alcohol abuse and dependence in an intensive 6 wk daily outpatient program using high-abundance plasma protein immunodepletion and LC-MS/MS techniques. Protein identification, quantification, candidate biomarker selection, and prioritization analyses were carried out. Among the 246 quantified serum proteins, abundance of 13 and 45 proteins in female and male subjects were significantly changed (p ≤ 0.05), respectively. Of these biomarker candidate proteins, 2 (female) and 8 (male) proteins were listed in category 1, with high area under the receiver operating characteristic curve, sensitivity, specificity, and fold change. In summary, several new biomarker candidates have been identified to monitor abstinence from alcohol abuse.

Keywords: Alcohol Abuse; Biomarker; MS/MS; Proteomics.

Figure 1

Among the 30 proteins from male subjects that were submitted to IPA, 13 and 6 proteins are included in networks 1 and 2, respectively. Top diseases and functions involved in network 1 are cellular movement, hematological system development and function, and immune cell trafficking. Top diseases and functions involved in network 2 are lipid metabolism, molecular transport, and small molecule biochemistry.

Figure 2

The ROC curve, sensitivity and specificity, and box plot of APOC1 in female subjects. Its AUC is 0.906 with a sensitivity of 0.875 and specificity of 1.000, indicating that it is a good biomarker candidate.

Figure 3

The ROC curve, sensitivity and specificity, and box plot of APOD in female subjects. The AUC of APOD is 0.891 with a sensitivity of 0.750 and specificity of 0.875, establishing it as a good biomarker candidate.