RESUMO
Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.
RESUMO
Ovarian cancer (OC) is a major cause of cancer mortality in women worldwide. Due to the occult onset of OC, its nonspecific clinical symptoms in the early phase, and a lack of effective early diagnostic tools, most OC patients are diagnosed at an advanced stage. In this study, shallow whole-genome sequencing was utilized to characterize fragmentomics features of circulating tumor DNA (ctDNA) in OC patients. By applying a machine learning model, multiclass fragmentomics data achieved a mean area under the curve (AUC) of 0.97 (95% CI 0.962-0.976) for diagnosing OC. OC scores derived from this model strongly correlated with the disease stage. Further comparative analysis of OC scores illustrated that the fragmentomics-based technology provided additional clinical benefits over the traditional serum biomarkers cancer antigen 125 (CA125) and the Risk of Ovarian Malignancy Algorithm (ROMA) index. In conclusion, fragmentomics features in ctDNA are potential biomarkers for the accurate diagnosis of OC.