Context Exosomal miRNAs are considered potential non-invasive biomarkers for thyroid cancer. However, the global exosomal miRNAs profile for papillary thyroid cancer (PTC) has not been revealed. Objective This study investigated the diagnostic value of plasma and serum exosomal miRNAs for PTC. Methods Plasma and serum samples were collected from ten patients with benign thyroid nodules and 17 with PTC for small RNA sequencing. Plasma samples were collected from two independent cohorts, including 119 patients with PTC, 51 healthy people and 82 patients with benign thyroid nodules, for validation by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Results Small RNA sequencing identified 41 putative exosomal miRNA biomarkers for PTC. Twelve miRNAs were selected for validation. miR-376a-3p, miR-4306, miR-4433a-5p, and miR-485-3p expression significantly increased in patients with PTC compared to that in healthy people and patients with benign thyroid nodules (P ˂ 0.05). Moreover, miR-485-3p and miR-4433a-5p presented larger areas under the curve (AUCs). The high expression of exosomal miR-485-3p correlated with tumor size greater than or equal to 1 cm, advanced clinical stage, extrathyroidal extension, BRAF mutation, and lymph node metastasis. Besides, miR-485-3p exhibited the highest AUCs in diagnosing PTC patients with high-risk factors. Conclusions Plasma exosomal miR-485-3p and miR-4433a-5p might serve as biomarkers for PTC diagnosis. Plasma exosomal miR-485-3p could enable discrimination between high-risk and low-risk PTC.

The expression and functions of microRNA (miR)-411 have been investigated in several types of cancer. However, until now, miR-411 in human breast cancer has not been examined. The present study investigated the expression, biological functions and molecular mechanisms of miR-411 in human breast cancer, discussing whether it offers potential as a therapeutic biomarker for breast cancer in the future. The expression levels of miR-411 in human breast cancer tissues and cells were measured using reverse transcription-quantitative polymerase chain reaction analysis. Following transfection with miR-411 mimics, an MTT assay, cell migration and invasion assay, western blot analysis and luciferase assay were performed in human breast cancer cell lines. According to the results, it was found that miR-411 was significantly downregulated in breast cancer, and associated with lymph node metastasis and histological grade. Additionally, it was observed that miR-411 suppressed cell growth, migration and invasion in the breast cancer cells. The present study also provided the first evidence, to the best of our knowledge, that miR-411 was likely to directly target specificity protein 1 in breast cancer. These findings indicated that miR-411 may be used a therapeutic biomarker for the treatment of breast cancer in the future.

Context Papillary thyroid cancer (PTC) has been one of the most frequent endocrine malignancies around the world. Although most PTC patients have a favorable prognosis, a subgroup of patients die, especially when disease recurrence occurs. There is a pressing need for clinically relevant preclinical thyroid cancer models for personalized therapy due to the lack of in vitro models that faithfully represent the biology of the parental tumors. Objective To understand thyroid cancer and translate this knowledge to clinical applications, the patient-derived PTC organoids as a promising new preclinical model were established. Design Surgically resected PTC primary tissues were dissociated and processed for organoid derivation. Tumor organoids were subsequently subjected to histological characterization, DNA-sequencing, drug screen, and cell proliferation assay, respectively. Results We describe a three-dimensional culture system for the long-term expansion of patient-derived PTC organoid lines. Notably, PTC organoids preserve the histopathological profiles and genomic heterogeneity of the originating tumors. Drug sensitivity assays of PTC organoids demonstrate patient-specific drug responses, and large correlations with the respective mutational profiles. Estradiol was shown to promote cell proliferation of PTC organoids in the presence of estrogen receptor α (ERα), regardless of the expression of estrogen receptor β (ERβ) and G protein-coupled estrogen receptor (GPER). Conclusions These data suggest that this newly developed PTC-derived organoids may be an excellent preclinical model for studying clinical response to anticancer drugs in a personalized way, as well as provide a potential strategy to develop the prevention and treatment options for thyroid cancer with ERα-specific antagonists.

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The breast cancer resistance protein (BCRP) is a recently characterized xenobiotic half-transporter protein that acts as an energy-dependent efflux pump and may be associated with the multidrug-resistant phenotype. The aim of this study was to determine the association between BCRP expression and 5-fluorouracil (5-FU) resistance in clinical breast cancer tissue specimens. The BCRP expression was investigated using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) by use of the Master SYBR-Green I reagent and immunohistochemistry (IHC) by use of the BXP-21 anti-BCRP monoclonal antibody in clinical breast cancer tissue specimens. Chemosensitivity to 5-FU for BCRP-positive clinical breast cancer tissue specimens was colorimetrically assessed with the cytotoxicity assay through methyl thiazolyl tetrazolium (MTT) reduction. A total of 37 BCRP-positive clinical breast cancer tissue specimens were identified with quantitative RT-PCR and IHC. There was a significant correlation in BCRP expression between the results of quantitative RT-PCR and IHC in the specimens. The fold resistance to 5-FU was 7–12 compared to sensitivity to paclitaxel as determined by the colorimetric assay through MTT reduction in the 37 specimens. Our study results indicated that 5-FU resistance may be mediated by BCRP expression in clinical breast cancer tissue specimens, which may help optimize the design of breast cancer clinical chemotherapy schemes in BCRP-positive specimens.