Risk factors for cervical lymph node metastasis in the central or lateral cervical region in medullary thyroid carcinoma: a systematic review and meta-analysis.

PURPOSE: Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was conducted to clarify the risk factors for cervical lymph node metastasis (central lymph node metastasis or lateral cervical lymph node metastasis) in MTC by meta-analysis, and to provide evidence-based basis for the treatment and prognosis of MTC. METHODS: The literatures related to cervical lymph node metastasis in medullary thyroid carcinoma were searched in PubMed, Embase, Web of Science, Cochrane, CNKI and Wanfang databases, and statistical analysis was performed using Revman 5.3 and Stata 14.0 software. RESULTS: A total of 28 papers were included in this paper, and meta-analysis showed that the occurrence of central lymph node metastasis (CLNM) in MTC patients was significantly associated with tumor size (OR = 3.07, 95%CI: 2.04-4.63, P < 0.00001), multifocality (OR = 0.29, 95%CI: 0.19-0.44, P < 0.00001), bilaterality (OR = 3.75, 95% CI: 1.95-7.14, P < 0.0001), capsular invasion (OR = 9.88, 95% CI: 5.93-16.45, P < 0.00001) and extrathyroidal extension (OR = 5.48, 95% CI: 2.61-11.51, P < 0.00001). While the occurrence of lateral cervical lymph node metastasis (LLNM) in MTC patients was strongly correlated with gender (OR = 2.97, 95%CI: 2.46-3.58, P < 0.00001), tumor size (OR = 3.88, 95%CI: 1.90-7.92, P = 0.0002 < 0.05), multifocality (OR = 0.43, 95%CI: 0.35-0.51, P < 0.00001), bilaterality (OR = 2.93, 95% CI: 1.72-4.98, P < 0.0001), capsular invasion (OR = 8.44, 95% CI: 6.11-11.64, P < 0.00001), extrathyroidal extension (OR = 7.04, 95% CI: 5.54-8.94, P < 0.00001), margin of the tumor (OR = 4.47, 95% CI: 2.37-8.44, P < 0.00001), shape of the tumor (OR = 6.81, 95% CI: 3.64-12.73, P < 0.00001), preoperative calcitonin level (SMD = 1.39, 95% CI: 0.98-1.80, P < 0.00001), preoperative carcinoembryonic antigen level (SMD = 0.97, 95% CI: 0.74-1.20, P < 0.00001) and CLNM (OR = 19.70, 95% CI: 14.16-27.43, P < 0.00001). CONCLUSION: Tumor size, multifocality, bilaterality, capsular invasion and extrathyroidal extension are the main risk factors for developing CLNM in MTC patients; And risk factors for developing LLNM in MTC patients include: gender, tumor size, multifocality, bilaterality, capsular invasion, extrathyroidal extension, margin of the tumor, shape of the tumor, preoperative calcitonin level, preoperative carcinoembryonic antigen level and central lymph node metastasis. These risk factors can guide the individualized treatment plan and improve the prognosis of MTC patients.

Exosomal microRNAs as novel diagnostic biomarkers in breast cancer: A systematic evaluation and meta-analysis.

Circulating tumor-derived exosomal microRNAs (miRNAs) play a key role in the development of cancer. We aimed to assess the diagnostic value of circulating exosomal miRNAs in breast cancer (BC). A computer search was conducted for clinical studies on exosomal miRNA diagnosis of breast cancer published in Wanfang, CNKI, China Biology Medicine disc, VIP, Web of Science, Cochrane Library, PubMed, and Embase built up to August 16, 2022. True/false positive (TP/FP) and true/false negative (TN/FN) rates were extracted from each eligible study to obtain pooled sensitivities, specificities, positive/negative likelihood ratios (PLR/NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95% CI). The meta-analysis included 7 articles including 348 Asian patients and 260 controls. All miRNAs were quantified using qRT-PCR assays. The sensitivity and specificity of the combination were 0.67 (95% CI = 0.64-0.71) and 0.81 (95% CI = 0.77-0.86), respectively. The combined DOR was 10.2 (95% CI = 6.00-16.74). The combined AUC(area under the subject operating characteristic curve) was 0.83 (0.91-0.96). In conclusion, exosomal-derived miRNA can be a good indicator to improve the diagnosis of breast cancer.

The predictive value of circular RNAs in the diagnosis, prognosis and clinicopathological features of thyroid cancer: A systematic review and meta-analysis.

OBJECTIVE: An increasing number of studies have reported circular RNAs (circRNAs) as new potential diagnostic and prognostic biomarkers for thyroid cancer. However, the overall predictive value of circRNAs for thyroid cancer remains unclear. Therefore, we performed a comprehensive meta-analysis to investigate the predictive value of circRNAs in the diagnosis, prognosis and clinicopathological features of thyroid cancer (TC). METHODS: PubMed, Embase, Cochrane library and Web of science were searched systematically. The search time limit was from the establishment of the database to October 2021. We used the subject words combined with free words for the search. Furthermore, we used Review Manager 5.3 and Meta-Disc1.4 for relevant data analysis, and Stata 13.1 for sensitivity analysis and publication bias test. The combined sensitivity and specificity were used to evaluate the diagnostic value of circRNAs. The hazard ratio (HR) and its 95% confidence interval (95%CI) were used for statistical analysis of the prognosis of TC. The clinical characteristics were analyzed with Odds Ratio (OR) and its 95% CI. P = 0.05 for all analysis, Q test and I2 analysis were used for heterogeneity evaluation, I2 ≤ 50% and Q test P > 0.1, indicated the lack of heterogeneity. RESULTS: A total of 26 eligible studies including 18 on clinicopathological studies, 7 on prognostic and 6 diagnostic studies were enrolled in our meta-analysis. A total of 1911 patients with TC were included. For the clinicopathological and prognostic value, the results showed that a high expression of circRNAs was correlated with poor clinical parameters, such as the tumor size [OR = 2.79, 95%CI (1.88, 4.13)], extra-glandular metastasis (ETE) [OR = 0.74, 95%CI (0.45, 1.53),P = 0.24], TNM staging [OR = 3.82, 95%CI (2.86, 5.10)], lymph node metastasis (LNM) [OR = 3.88, 95% (2.90, 5.19)], tumor focality [OR = 31.87, 95%CI (1.05, 3.31)] and poor overall survival (OS)[ HR = 1.97, 95%CI (1.37, 2.83)]. For the diagnostic value, the sensitivity, specificity and Area Under Curve (AUC) of the combined group were 0.83 [95%CI (0.77-0.87)], 0.77 [95%CI (0.71-0.82)] and 0.91 respectively. CONCLUSIONS：: CircRNAs have a potential diagnostic value for TC. Meanwhile, an elevated expression of circRNAs has been linked to a poor OS in TC patients, and it also associates with poor prognosis of thyroid cancer patients. The expression of circRNAs is also correlated with certain clinical characteristics, suggesting that it may have important clinical significance.

Molecular characterization, expression analysis of 14-3-3 beta/alpha and the effect of RNA interference on ion transporter protein Na+-K+-ATPase, Na+-H+-exchanger and CFTR in turbot (Scophthalmus maximus).

To understand the role of 14-3-3 beta/alpha in hypoosmotic regulation of turbot (Scophthalmus maximus), we characterized the 14-3-3 beta/alpha gene and analyzed the tissue distribution and its gene transcriptional patterns in the main expressed tissues under low salt stress. The 14-3-3 beta/alpha cDNA is 892 bp in length, incorporating an ORF of 774 bp with a putative primary structure of 257 residues. The deduced amino acid sequences shared highly conserved structures with other eukaryotes. Quantitative real-time PCR results showed that the 14-3-3 beta/alpha transcripts were widely expressed in various tissues of turbot, with most abundant in the gill (P < .05), to a lesser extent in the kidney, intestine, brain and spleen, and at low levels in the pituitary and other tissues examined. And the expression of turbot 14-3-3 beta/alpha exhibited a trend of increasing first and then decreasing with the time of stress under low salt stress, and the highest value appeared in 12 h (P < .05). After injecting different concentrations of dsRNA, the mRNA expression of 14-3-3 gene decreased significantly during the monitoring period, and the best interference effect was achieved 12 h after injecting 4 µg/g dsRNA. For the first time, the gene was silenced in fish by intramuscular injection of dsRNA. It also provides a new and effective way to study gene function at the individual level. Moreover, the mRNA interference of 14-3-3 beta/alpha would cause changes in the expression of several ion channel proteins, for example, the decrease of Na+-K+-ATPase and Na+-H+-exchanger and the increase of CFTR. As a result, 14-3-3 beta/alpha appears to be an important molecular regulator for osmosensory signal transduction in gill of turbot.