Salivary protein candidates for biomarkers of oral disorders in people with a crack cocaine use disorder

Abstract The use of cocaine and its main derivative, crack, can cause some systemic effects that may lead to the development of some oral disorders. Objective To assess the oral health of people with a crack cocaine use disorder and identify salivary protein candidates for biomarkers of oral disorders. Methodology A total of 40 volunteers hospitalized for rehabilitation for crack cocaine addiction were enrolled; nine were randomly selected for proteomic analysis. Intraoral examination, report of DMFT, gingival and plaque index, xerostomia, and non-stimulated saliva collection were performed. A list of proteins identified was generated from the UniProt database and manually revised. Results The mean age (n=40) was 32 (±8.88; 18–51) years; the mean DMFT index was 16±7.70; the mean plaque and gingival index were 2.07±0.65 and 2.12±0.64, respectively; and 20 (50%) volunteers reported xerostomia. We identified 305 salivary proteins (n=9), of which 23 were classified as candidate for biomarkers associated with 14 oral disorders. The highest number of candidates for biomarkers was associated with carcinoma of head and neck (n=7) and nasopharyngeal carcinoma (n=7), followed by periodontitis (n=6). Conclusions People with a crack cocaine use disorder had an increased risk of dental caries and gingival inflammation; less than half had oral mucosal alterations, and half experienced xerostomia. As possible biomarkers for 14 oral disorders, 23 salivary proteins were identified. Oral cancer and periodontal disease were the most often associated disorders with biomarkers.


Introduction
The use of cocaine and its main derivative, crack, has become a huge public health concern worldwide due to the medical, psychological, and social issues associated with its abuse. The estimation of people using cocaine worldwide is 17 to 20 million. 1 The systemic effects of crack cocaine addiction include cardiovascular, neurological, respiratory, pulmonary, and gastrointestinal complications. 2 People with a cocaine use disorder have a high prevalence of anorexia and malnutrition, which may lead to the development of secondary lesions in the oral mucosa, 3,4 with glossalgia, angular cheilitis, and other forms of candidiasis being the most common. [5][6][7] Several studies have reported alteration in taste perception in people with a crack cocaine use disorder. 8 Cytological examinations have shown alterations in their mucosal cells, suggesting DNA damage, inflammation, enucleated cell enlargement, and in the number of nucleolar organizer regions. In addition to inflammation, these results suggest intense tissue proliferation and differentiation, disregarding drug aggression. [9][10][11][12] Human tissues and biological fluids contain proteins and other molecules that can be used as biomarkers.
The comparative and mass spectrometry-based proteomic analysis of body fluids can be particularly instrumental for the targeted identification of novel protein biomarkers with pathological relevance. 13 A biomarker can be defined as an indicator of physiological process, disease, or response to a therapeutic agent. 14,15 Although the presence or change in concentration of a biomarker is detected during a disease process, it does not guarantee disease occurrence. Careful evaluation of clinical parameters in the patient should be considered. 16 Saliva is an excellent diagnostic fluid due to its noninvasive method of collection; 17,18 the proximity to tumors of the head and neck offers great potential for biomarker detection in saliva. Proteomic analysis of this fluid allows identification of proteins that function as early diagnostic tools or prognostic markers for diseases. 17 Table 1 shows all clinical changes along with the drug use profile, PI, and GI of the participants.
The nine individuals selected for salivary proteomics analysis had a mean age of 36.39 (±7.78; 28-51) years. A total of 305 salivary proteins were identified by proteomic analysis. From that, 32 proteins were found to be candidate for biomarkers of oral disorders; 19 different oral disorders were identified.
After manual review, all articles related to "pleomorphic adenoma of salivary gland," which focused on other types of adenomas, were excluded since the biomarkers were not related to oral disorders   index, in addition to the presence of dental plaque and gingival inflammation, which agrees with other studies conducted on similar populations and age groups. 31,32 The study sample presented a gingival index (score 2) indicating moderate inflammation (score 2) without a large accumulation of dental biofilm. These clinical findings may explain the presence of salivary protein biomarkers of gingivitis, periodontitis, periodontal disease, and periodontal pocket in the tested sample.
In this study, a biomarker for hyposalivation (Spectrin alpha -A0A1B0GV13) was identified by salivary proteomics analysis, which agrees with a high The albumin biomarker (P02768) was related to leukoplakia, as reported in two previous studies. 37,38 Tobacco use is associated with a decrease in serum albumin concentration, as this protein is reduced in Upon manual review, we found that some biomarkers were associated with other diseases or were mentioned in the articles but not related to the target process of the study. This suggests that while researchers can use these search tools for preanalysis, the results should be critically and manually checked before being included in their review. Another

Conflict of interest
The authors declare no conflict of interest.

Data availability statement
All data generated and analyzed during this study are included in this published article.