Introduction—heterogeneity in clinical outcomes and survival was observed in patients with papillary thyroid cancer (PTC) and distant metastases. Here, we investigated the effect of distant metastases sites on survival in PTC patients. Methods—patients with a diagnosis of PTC and known metastases were identified using the Surveillance, Epidemiology, and End Results database (1975–2016). Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on thyroid cancer-specific survival (TCSS) and overall survival (OS). Results—from 89,694 PTC patients, 1819 (2%) developed distant metastasis at the initial diagnosis, of whom 26.3% presented with the multiple-organ disease. The most common metastatic sites were lung (53.4%), followed by bone (28.1%), liver (8.3%), and brain (4.7%). In metastatic patients, thyroid cancer-specific death accounted for 73.2%. Kaplan–Meier curves showed decreased OS in patients with metastases to the brain (median OS = 5 months) and liver (median OS = 6 months) compared to lung (median OS = 10 months) and bone (median OS = 23 months). Moreover, multiple organ metastasis had a higher mortality rate (67.4%) compared to single organ metastasis (51.2%, p < 0.001). Using multivariate analysis, risk factors that significantly influence TCSS and OS were male gender (HR = 1.86, 95% CI = 1.17–2.94, p < 0.001, and HR = 1.90, 95% CI = 1.40–2.57, p = 0.009), higher tumor grade (HR = 7.31, 95% CI = 2.13–25.0, p < 0.001 and HR = 4.76, 95% CI = 3.93–5.76, p < 0.001), multiple organ involvement (HR = 6.52, 95% CI = 1.50–28.39, p = 0.026 and HR = 5.08, 95% CI = 1.21–21.30, p = 0.013), and brain metastasis (HR = 1.82, 95% CI = 1.15–2.89, p < 0.001 and HR = 4.21, 95% CI = 2.20–8.07, p = 0.010). Conclusion—the pattern of distant metastatic organ involvement was associated with variability in OS in PTC. Multi-organ metastasis and brain involvement are associated with lower survival rates in PTC. Knowledge of the patterns of distant metastasis is crucial to personalize the treatment and follow-up strategies.

Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis. Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCa-derived exosomes and the TME remains only partially understood. In this review, we provide new insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the molecular mechanisms of TME reprogramming by exosomes draws more practical and universal conclusions for the development of new therapeutic interventions when considering TME in the treatment of PCa patients.

Circulatory tumor-derived exosomal microRNAs (miRNAs) play key roles in cancer development/progression. We aimed to assess the diagnostic/prognostic value of circulating exosomal miRNA in thyroid cancer (TC). A search in PubMed, Scopus, Web of Science, and Science Direct up to 22 May 2021 was performed. The true/false positive (TP/FP) and true/false negative (TN/FN) rates were extracted from each eligible study to obtain the pooled sensitivity, specificity, positive/negative likelihood ratios (PLR/NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95%CIs). The meta-analysis included 12 articles consisting of 1164 Asian patients and 540 controls. All miRNAs were quantified using qRT-PCR assays. The pooled sensitivity was 82% (95%CI = 77–86%), pooled specificity was 76% (95%CI = 71–80%), and pooled DOR was 13.6 (95%CI = 8.8–21.8). The best biomarkers with high sensitivity were miR-16-2-3p (94%), miR-223-5p (91%), miR-130a-3p (90%), and miR182-5p (94%). Similarly, they showed high specificity, in addition to miR-34c-5p. Six panels of two to four exosomal miRNAs showed higher diagnostic values with an area under the curve (AUC) ranging from 0.906 to 0.981. The best discriminative ability to differentiate between cancer and non-cancer individuals was observed for miR-146b-5p + miR-223-5p + miR-182-5p (AUC = 0.981, sensitivity = 93.8% (84.9–98.3), specificity = 92.9% (76.5–99.1)). In conclusion, the expression levels of exosomal miRNAs could predict TC.

Cancer remains a major public health concern, mainly because of the incompletely understood dynamics of molecular mechanisms for progression and resistance to treatments. The link between melanoma and thyroid cancer (TC) has been noted in numerous patients. Nucleocytoplasmic transport of oncogenes and tumor suppressor proteins is a common mechanism in melanoma and TC that promotes tumorigenesis and tumor aggressiveness. However, this mechanism remains poorly understood. Papillary TC (PTC) patients have a 1.8-fold higher risk for developing cutaneous malignant melanoma than healthy patients. Our group and others showed that patients with melanoma have a 2.15 to 2.3-fold increased risk of being diagnosed with PTC. The BRAF V600E mutation has been reported as a biological marker for aggressiveness and a potential genetic link between malignant melanoma and TC. The main mechanistic factor in the connection between these two cancer types is the alteration of the RAS-RAF-MEK-ERK signaling pathway activation and translocation. The mechanisms of nucleocytoplasmic trafficking associated with RAS, RAF, and Wnt signaling pathways in melanoma and TC are reviewed. In addition, we discuss the roles of tumor suppressor proteins such as p53, p27, forkhead O transcription factors (FOXO), and NF-_KB within the nuclear and cytoplasmic cellular compartments and their association with tumor aggressiveness. A meticulous English-language literature analysis was performed using the PubMed Central database. Search parameters included articles published up to 2021 with keyword search terms melanoma and thyroid cancer, BRAF mutation, and nucleocytoplasmic transport in cancer.

Previously, we demonstrated that inhibition of poly(ADP-ribose) polymerase (PARP) exerts protective effects against high-fat (HF) diet-induced atherogenesis in part by increasing tissue inhibitor of metalloproteinase (TIMP)-2 expression. Given that characteristics of dilated cardiomyopathy closely associate with atherosclerosis and are mediated by an imbalance between matrix metalloproteinases (MMPs) and TIMPs, we hypothesized that PARP-1 gene deletion may protect against HF-induced cardiac hypertrophy and dilatations by altering TIMP-2/MMPs balance in favor of a maintenance of tissue homeostasis. Hemodynamic parameters determined by echocardiography were similar in ApoE(-/-) mice and PARP-1-deficient ApoE(-/-) mice (DKO) fed a regular diet (RD). However, histological analysis revealed that cardiomyocytes of ApoE(-/-) mice on RD were hypertrophied, displaying an enlarged cell body and nucleus, traits that were absent in DKO animals. HF diet-fed ApoE(-/-) mice exhibited increased interventricular septum, left ventricular (LV) internal dimension, LV volume, and LV mass in addition to a separation of myocardial fibers suggestive of dilated cardiomyopathy. PARP-1 gene deletion protected against these degenerative changes. MMP activity was dramatically increased in hearts of ApoE(-/-) mice on HF diet and was accompanied by increased collagen degradation, mast cell degranulation, and increased myocyte cell death. PARP-1 gene knockout was associated with increased TIMP-2 expression antagonizing, as a result, the damaging effects of active MMPs. The present study demonstrates that PARP-1 gene deletion exerts protective effects against HF diet-induced dilated cardiomyopathy by maintaining increased expression of TIMP-2. With additional protective effects against cell death and inflammation, PARP-1 deficiency preserves cardiac tissue homeostasis.

Papillary thyroid carcinomas (PTCs) account for most endocrine tumors; however, screening and diagnosing the recurrence of PTC remains a clinical challenge. Using microRNA sequencing (miR-seq) to explore miRNA expression profiles in PTC tissues and adjacent normal tissues, we aimed to determine which miRNAs may be associated with PTC recurrence and metastasis. Public databases such as TCGA and GEO were utilized for data sourcing and external validation, respectively, and miR-seq results were validated using quantitative real-time PCR (qRT-PCR). We found miR-145 to be significantly downregulated in tumor tissues and blood. Deregulation was significantly related to clinicopathological features of PTC patients including tumor size, lymph node metastasis, TNM stage, and recurrence. In silico data analysis showed that miR-145 can negatively regulate multiple genes in the TC signaling pathway and was associated with cell apoptosis, proliferation, stem cell differentiation, angiogenesis, and metastasis. Taken together, the current study suggests that miR-145 may be a biomarker for PTC recurrence. Further mechanistic studies are required to uncover its cellular roles in this regard.