In this study, serum metabolic profiling of patients diagnosed with papillary thyroid carcinoma (PTC) and benign thyroid pathologies (BT) aimed to identify specific biomarkers and altered pathways when compared with healthy controls (C). The blood was collected after a histological confirmation from PTC (n = 24) and BT patients (n = 31) in parallel with healthy controls (n = 81). The untargeted metabolomics protocol was applied by UHPLC-QTOF-ESI⁺-MS analysis and the statistical analysis was performed using the MetaboAnalyst 5.0 platform. The partial least squares-discrimination analysis, including VIP values, random forest graphs, and heatmaps (p < 0.05), was complemented with biomarker analysis (with AUROC ranking) and pathway analysis, suggesting a model for abnormal metabolic pathways in PTC and BT based on 166 identified metabolites. There were 11 classes of putative biomarkers selected that were involved in altered metabolic pathways, e.g., polar molecules (amino acids and glycolysis metabolites, purines and pyrimidines, and selenium complexes) and lipids including free fatty acids, bile acids, acylated carnitines, corticosteroids, prostaglandins, and phospholipids. Specific biomarkers of discrimination were identified in each class of metabolites and upregulated or downregulated comparative to controls, PTC group, and BT group. The lipidomic window was revealed to be more relevant for finding biomarkers related to thyroid carcinoma or benign thyroid nodules, since our study reflected a stronger involvement of lipids and selenium-related molecules in metabolic discrimination.

There are still many questions remaining about the etiopathogenesis of thyroid cancer, the most common type of endocrine neoplasia. Numerous occupational and environmental exposures have been shown to represent important risk factors that increase its incidence. Updated information about thyroid cancer diagnostics related to occupational and environmental risk factors is reviewed here, considering an integrated risk assessment approach; new data concerning thyroid cancer etiology and pathogenesis mechanisms, diagnostic biomarkers and methodologies, and risk factors involved in its pathogenesis are presented. A special emphasis is dedicated to specific occupational risk factors and to the association between environmental risk agents and thyroid cancer development. The occupational environment is taken into consideration, i.e., the current workplace and previous jobs, as well as data regarding risk factors, e.g., age, gender, family history, lifestyle, use of chemicals, or radiation exposure outside the workplace. Finally, an integrative approach is presented, underlying the need for an accurate Risk Assessment Matrix based on a systematic questionnaire. We propose a complex experimental design that contains different inclusion and exclusion criteria for patient groups, detailed working protocols for achieving coherent and sustainable, well-defined research stages from sample collection to the identification of biomarkers, with correlations between specific oncometabolites integrated into the Risk Assessment Matrix.

Background: Identification of specific urine metabolic profiles for patients diagnosed with papillary thyroid carcinoma (TC) vs. benign nodules (B) to identify specific biomarkers and altered pathways compared to those of healthy controls (C). Methods: Patient urine samples were collected, before surgery and after a histological confirmation of TC (n = 30) and B (n = 30), in parallel with sample collection from healthy controls (n = 20). The untargeted and semi-targeted metabolomic protocols were applied using UPLC-QTOF-ESI⁺-MS analysis, and the statistical analysis was performed using the Metaboanalyst 6.0 platform. The results for the blood biomarkers, previously published, were compared with the data obtained from urine sampling using the Venny algorithm and multivariate statistics. Results: Partial least squares discrimination, including VIP values, random forest graphs, and heatmaps (p < 0.05), together with biomarker analysis (AUROC ranking) and pathway analysis, suggested a specific model for the urinary metabolic profile and pathway alterations in TC and B vs. C, based on 190 identified metabolites in urine that were compared with the serum metabolites. By semi-targeted metabolomics, 10 classes of metabolites, considered putative biomarkers, were found to be responsible for specific alterations in the metabolic pathways, from polar molecules to lipids. Specific biomarkers for discrimination were identified in each class of metabolites that were either upregulated or downregulated when compared to those of the controls. Conclusions: The lipidomic window was the most relevant for identifying biomarkers related to thyroid cancer and benign conditions, since this study detected a stronger involvement of lipids and selenium-related molecules for metabolic discrimination.

Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP, but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.

Desmoid tumors are rare mesenchymal neoplasms arising from locally invasive fibroblasts. While they lack metastatic potential, they exhibit high local recurrence rates and can cause significant tissue destruction. We present the case of a 39-year-old female patient who initially presented with epigastric pain, pyrosis, and a palpable, firm, painless mass in the left upper quadrant, extending to the left hemithorax. Her medical history included treated cervical neoplasia. Clinical evaluation, imaging studies, and histopathological analysis suggested aggressive fibromatosis. The patient opted for a partial surgical excision, which resulted in tumor recurrence one year later, with infiltration of the ribs near the sternum. Despite oncological recommendations favoring conservative management, she opted for a second surgical intervention, involving an en-bloc resection of the tumor, the affected sternum and ribs, followed by thoracic wall reconstruction.

Desmoid tumors are rare mesenchymal neoplasms arising from locally invasive fibroblasts. While they lack metastatic potential, they exhibit high local recurrence rates and can cause significant tissue destruction. We present the case of a 39-year-old female patient who initially presented with epigastric pain, pyrosis, and a palpable, firm, painless mass in the left upper quadrant, extending to the left hemithorax. The patient’s medical history included treated cervical neoplasia. Clinical evaluation, imaging studies, and histopathological analysis suggested aggressive fibromatosis. The patient opted for a surgical excision, which resulted in tumor recurrence one year later, with infiltration of the ribs near the sternum. Despite oncological recommendations favoring conservative management, the patient opted for a second surgical intervention, involving an en-bloc resection of the tumor and the affected sternum and ribs, followed by thoracic wall reconstruction.