Papillary Thyroid Carcinoma: Correlation Between Molecular and Clinical Features.

BACKGROUND: Thyroid cancer is prevalent worldwide, including in China, where its incidence is on the rise. Papillary thyroid carcinoma (PTC) is the predominant subtype. Investigating the relationship between clinical data associated with PTC and gene mutations is crucial for improving detection and treatment. PATIENTS AND METHODS: We collected samples and associated clinical data from 700 PTC patients at Shanxi Provincial People's Hospital. Using a panel of 57 genes linked to thyroid cancer, we sequenced the samples to determine the mutation frequency of thyroid cancer-associated genes in PTC. We further analyzed the correlation between gene variants and clinical information. RESULTS: The mean age of patients in this study was 42.5 years. Females predominated, comprising 507 of the total patient population, resulting in a female-to-male ratio of 2.63 (507:193). Tumor distribution revealed 198, 257, and 142 cases on the left, right, and both sides, respectively. Among the 57 thyroid cancer-related genes analyzed, we identified at least one driver gene in 83.6% of patients. Notably, 76.4% had BRAF mutations, mainly BRAFV600E, which constituted 90.9% of all BRAF mutations, with 535 cases exhibiting these mutations. Other significant driver genes included CHEK2 (n = 84), RET (n = 42), PIK3CA (n = 7), and EGFR (n = 7). RET fusions (n = 28) were also identified. Notably, patients under 55 years old exhibit a higher tendency towards advanced N staging, suggesting that younger individuals may be more prone to lymph node metastasis. Additionally, male patients were more likely to have advanced N stages. Importantly, a positive correlation was observed between higher BRAF allele frequencies and more advanced T and N stages. Similarly, correlation analysis revealed that a greater frequency of RET fusions correlated with later T and N stages. CONCLUSION: This study uncovered several significant insights. Younger PTC patients exhibited a higher propensity for lymph node metastasis. An elevated mutation frequency of BRAF was correlated with a higher occurrence of RET fusions, predisposing individuals to lymph node metastasis and potentially indicating a poorer prognosis.

Rh(III)-Catalyzed [4 + 1] Annulation of Benzamides with Vinyl Cyclic Carbonates for the Synthesis of Isoindolinones.

A Rh(III)-catalyzed C-H bond activation and subsequent [4+1] annulation of benzamides with vinyl cyclic carbonates have been developed for the synthesis of isoindolinones, in which the electron-rich alkenes could serve as one-carbon units. This reaction proceeds smoothly with high regioselectivity under oxidant- and silver-free conditions and exhibits broad substrate scope and functional group tolerance including some biological active materials. The scale-up reaction and derivatizations of the product further demonstrate the potential synthetic utility of this transformation.

Evaluating personalized circulating tumor DNA detection for early-stage lung cancer.

Circulating tumor DNA (ctDNA) has been widely used as a minimally invasive biomarker in clinical routine. However, a number of factors such as panel design, sample quality, patients' disease stages are known to influence ctDNA detection sensitivity. In this study, we systematically evaluated common factors associated with the variability of ctDNA detection in plasma and investigated ctDNA abundance in bronchoalveolar lavage (BAL). Whole exome profiling was conducted on 61 tumor tissue samples to identify tumor-specific variants, which were then used to design personalized assay MarRyDa® for ctDNA detection. DNA extracted from BAL fluid and plasma were genotyped using MarRyDa® platform. Our analysis showed that histological subtypes and disease stages had significant differences in ctDNA detection rate. Furthermore, we found that DNA purified from BAL supernatants contains the highest levels of ctDNA compared with BAL precipitates and plasma; therefore, utilizing BAL supernatants for tumor detection might provide additional benefits. Finally, we demonstrated that tumor cellularity played significant roles in the design of personalized ctDNA panel which eventually impacts ctDNA detection sensitivity. We suggest setting a flexible criteria for sample quality control and utilization of BAL might benefit more patients in clinics.

Climate change fostered rise and fall of the Tibetan Empire during 600-800 AD.

During the 7-9th century, the Tibetan Empire constituted a superpower between the Tang Empire and Abbasid Caliphate: one that played significant roles in geopolitics in Asia during the Early Medieval Period. The factors which led to the rise and rapid decline of this powerful Empire, the only united historical regime on the Tibetan Plateau (TP), remain unclear. Sub-annual scale precipitation and decadal-scale temperature records of the central TP are presented, indicating that the height of this Empire coincided with a two-century long interval of uncharacteristically warm and humid climate. The ameliorated climate enabled the expansion of arable land and increased agricultural production. The close relationship between the precipitation records and historical events implied that the Empire implemented flexible strategies to tackle the effects of climate changes. This has implications for agricultural production in alpine regions including the TP, in the context of current global warming.

[Retracted] MicroRNA­509 targets PAX6 to inhibit cell proliferation and invasion in papillary thyroid carcinoma.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that several of the panels shown for the cell invasion assays in Figs. 2C and 5D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 1403­1409, 2019; DOI: 10.3892/mmr.2018.9750].

CircSND1/miR-182-5p Axis Promotes Proliferative and Invasive Abilities of Thyroid Cancer via Binding Targeting MET.

Objective: To monitor the impacts of circSND1 upon thyroid cancer (TC) tissues and cells and its mechanisms. Methods: Thiazole blue (MTT) was adopted to monitor the impacts of circSND1 upon the proliferative abilities of TPC-1 and SW1736 cells. 5-Bromodeoxyuridine (BrdU) combined with flow cytometry was adopted to monitor the impacts of circSND1 upon the DNA synthesis of TPC-1 and SW1736 cells. We adopted transwell experiment to examine the impacts of circSND1 on cell invasive abilities of TPC-1 and SW1736 cells. The mRNA quantitative levels of circSND1, miR-182-5p, and mesenchymal epidermal transformation factor (MET) in TC tissues were detected by qRT-PCR experiment. We also adopted luciferase assay to verify the targeting interaction between miR-182-5p and MET or miR-182-5p and circSND1. Results: CircSND1 mRNA and MET mRNA were upregulated in thyroid cancer tissues. MiR-182-5p quantification was attenuated in thyroid cancer tissues. Downregulation of circSND1 suppressed TC progression in vivo and in vitro. Furthermore, luciferase report assay uncovered that miR-182-5p was a direct binding target of circSND1 and MET was a direct binding target of miR-182-5p. Besides, circSND1 regulated MET expression and thyroid cancer cell function via binding miR-182-5p. Conclusion: Overexpression of circSND1 in TC tissues and cells facilitates TC tumorigenesis and metastasis via suppressing the quantitative level of miR-182-5p and inducing the upregulation of MET mRNA and protein expression, which expected to offer fresh clues for the administration of TC.

Oncolytic Vaccinia Virus-Mediated Antitumor Effect and Cell Proliferation Were Promoted in PTC by Regulating circRNA_103598/miR-23a-3p/IL-6 Axis.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy, and cases have been rising steadily worldwide in the past few decades. Despite great progress having been made in surgery and chemotherapy for PTC, the survival rate of PTC patients has not increased significantly. Therefore, there is an urgent need to explore novel treatment strategies. MATERIALS AND METHODS: The levels of circRNA_103598, miR-23a-3p and IL-6 mRNA in PTC tissues and cells were examined by qRT-PCR assay. Cell proliferation and IC50 values of oncolytic vaccinia virus (OVV) were detected by CCK-8 assay. A dual-luciferase reporter assay was performed to detect the relationships among circRNA_103598, miR-23a-3p and IL-6. ELISA was carried out to detect the expression of IL-6. RESULTS: We found that circRNA_103598 was increased in PTC tissues and cell lines and acted as a sponge for miR-23a-3p. Moreover, knockdown of miR-23a-3p suppressed the OVV-mediated antitumor effect and cell proliferation in PTC. In addition, we revealed that circRNA_103598 bound to miR-23a-3p as a sponge to promote IL-6 expression. CONCLUSION: Our study first revealed the high expression and oncogenic function of circRNA_103598 in PTC cells. Then, circRNA_103598 sponged miR-23a-3p to upregulate IL-6 expression, with the resulted that cell proliferation was promoted and the OVV-mediated antitumor effect was enhanced by strengthening the viral replication, providing new insights into future therapy for PTC.

Alteration of the abundance of Parvimonas micra in the gut along the adenoma-carcinoma sequence.

Parvimonas micra (P. micra) is reported to be associated with colorectal cancer (CRC). However, its association with colorectal adenoma (CRA) and its role in the initiation of colorectal tumors remain unknown. The present study aimed to clarify the relationship between P. micra and CRA and CRC by exploring the changes of P. micra abundance in an adenoma-carcinoma sequence in a new cohort and 4 public sequencing datasets. To investigate the alterations of P. micra abundance in the gut along the adenoma-carcinoma sequence, quantitative PCR (qPCR) was conducted to measure the relative abundance of P. micra in fecal samples from 277 subjects (128 patients with CRA, 66 patients with CRC and 83 healthy individuals, as controls) who underwent colonoscopy as outpatients. Then, the relative abundance of P. micra was analyzed in fecal samples from 596 subjects (185 healthy controls, 158 CRC, 253 CRA) in four public 16S rRNA sequencing datasets. The qPCR results demonstrated that the CRA group had an abundance of P. micra (P=0.2) similar to that of the healthy control group, while the CRC group had a significantly increased abundance (P=8.2×10-11). The level of P. micra effectively discriminated patients with CRC from healthy controls, while it poorly discriminated patients with CRA from healthy controls; with an area under the receiver operating characteristic curve of 0.867 for patients with CRC and 0.554 for patients with CRA. The same pattern of the alteration of P. micra abundance, which was low in healthy controls and patients with CRA but elevated in patients with CRC, was found in all four public sequencing datasets. These results suggested that P. micra was closely associated with, and may serve as a diagnostic marker for, CRC but not CRA. Moreover, it was indicated that P. micra may be an opportunistic pathogen of CRC, which may promote CRC development but serve a limited role in tumorigenesis.

MicroRNA­509 targets PAX6 to inhibit cell proliferation and invasion in papillary thyroid carcinoma.

MicroRNAs (miRNAs/miRs) negatively regulate the expression of numerous genes and therefore contribute to the occurrence and development of papillary thyroid carcinoma (PTC). Hence, further investigation into the specific roles of miRNAs in PTC is valuable for developing effective therapeutic methods for patients with this disease. MiRNA­509 is dysregulated and serves pivotal roles in several types of human cancer; however, the expression and roles of miR­509 in PTC and its underlying mechanism require further investigation. In the present study, the expression of miR­509 in PTC tissues and cell lines was detected and the specific functions of miR­509 in the progression of PTC were investigated. Additionally, the molecular mechanisms underlying the action of miR­509 in PTC were determined. The present study demonstrated that miR­509 was significantly downregulated in PTC tissues and cell lines. MiR­509 upregulation inhibited the PTC cell proliferation and invasion. Mechanistically, paired box 6 (PAX6) was identified as a novel target of miR­509 in PTC cells. In clinical PTC samples, miR­509 was significantly overexpressed and inversely correlated with PAX6 expression. PAX6 restoration effectively reversed the inhibitory effects of miR­509 overexpression on PTC cell proliferation and invasion. These results demonstrated that miR­509 may act as a tumor suppressor in PTC by directly targeting PAX6. Thus, miR­509 may be a potential therapeutic target for the treatment of patients with PTC.

miR­205 targets YAP1 and inhibits proliferation and invasion in thyroid cancer cells.

MicroRNA­205 (miR­205) has been reported to be downregulated, and serves critical roles in the pathogenesis and progression of several types of cancer, including breast, prostate and lung cancer. However, the underlying mechanism of miR­205 in thyroid cancer remains unclear. In the present study, it was demonstrated that the expression of miR­205 was reduced in thyroid cancer tissues compared with non­cancer tissues. In addition, miR­205­knockdown models in the BHT­101 cell line and ectopic expression models in the 8505­C cell line were used to measure the biological functions of miR­205. The results indicated that miR­205 inhibited certain aspects of thyroid cancer, including cell proliferation, migration and invasion. Furthermore, Yes­associated protein 1 (YAP1) was identified as a target gene of miR­205 and its expression was negatively correlated with that of miR­205 in thyroid cancer tissues. Depletion of YAP1 partially reduced the anti­miR­205­induced cell growth and invasion. The results of the present study suggested that the tumor suppressive functions of miR­205 via targeting YAP1 could be a novel target for the treatment of thyroid cancer.