Purpose Central lymph node metastasis (CNM) are highly prevalent but hard to detect preoperatively in papillary thyroid carcinoma (PTC) patients, while the significance of prophylactic compartment central lymph node dissection (CLND) remains controversial as a treatment option. We aim to establish a nomogram assessing risks of CNM in PTC patients, and explore whether prophylactic CLND should be recommended. Materials and Methods One thousand four hundred thirty-eight patients from two clinical centers that underwent thyroidectomy with CLND for PTC within the period 2016-2019 were retrospectively analyzed. Univariate and multivariate analysis were performed to examine risk factors associated with CNM. A nomogram for predicting CNM was established, thereafter internally and externally validated. Results Seven variables were found to be significantly associated with CNM and were used to construct the model. These were as follows: thyroid capsular invasion, multifocality, creatinine > 70 μmol/L, age < 40, tumor size > 1 cm, body mass index < 22, and carcinoembryonic antigen > 1 ng/mL. The nomogram had good discrimination with a concordance index of 0.854 (95% confidence interval [CI], 0.843 to 0.867), supported by an external validation point estimate of 0.825 (95% CI, 0.793 to 0.857). A decision curve analysis was made to evaluate nomogram and ultrasonography for predicting CNM. Conclusion A validated nomogram utilizing readily available preoperative variables was developed to predict the probability of central lymph node metastases in patients presenting with PTC. This nomogram may help surgeons make appropriate surgical decisions in the management of PTC, especially in terms of whether prophylactic CLND is warranted.
Unveiling key oncogenic events in malignancies is the key to improving the prognosis and therapeutic outcome of malignancies. Lines of evidence have shown that super-enhancers control the expression of genes that determine the cell fate, but the oncogenic super-enhancers in colorectal cancer (CRC) and their impact on carcinogens remain largely unexplored. Here, we identified a new oncogenic super-enhancer-regulated gene, IL-20RA, in CRC. Using the integrative analysis of H3K27ac ChIP-seq and RNA-seq in CRC tumors and normal colon tissues, we obtained a series of oncogenic super-enhancers in CRC. We found that super-enhancer inhibition by JQ-1 or iBET-151 suppressed the growth of tumor cells and inhibited the expression of IL-20RA. We found that IL-20RA was highly expressed in the tumor tissue of CRC and related to the advanced stage. Further functional studies showed that knockdown of IL-20RA inhibited the growth and metastasis of CRC. In addition, we found that IL-20RA was involved in regulating oncogenic and immune pathways and affecting the expression of genes related to cell proliferation and immune evasion in CRC. Together, our study demonstrated a novel oncogene in CRC and shed new light on oncogenic super-enhancer contributions to cell proliferation and immune escape.
Skip metastasis is a specific type of papillary thyroid cancer lymph node metastasis (LNM). The present study aimed to clarify the typical clinical characteristics of skip metastasis and optimize the prediction model, so as to provide a more individual treatment mode for skip metastasis. We retrospectively analyzed 1075 PTC patients with different lymph node metastasis statuses from two clinical centers. Comparisons have been made between patients with skip metastasis and other types of LNM. Univariate and multivariate analyses were performed to detect the risk factors for skip metastasis with negative LNM, and a nomogram for predicting skip metastasis was established. The rate of skip metastasis was 3.4% (37/1075). Compared with other types of LNM, significant differences showed in tumor size, upper portion location, thyroid capsular invasion, and ipsilateral nodular goiter with the central lymph node metastasis (CLNM) group, and in age and gender with the lateral lymph node metastasis (LLNM) group. Four variables were found to be significantly associated with skip metastasis and were used to construct the model: thyroid capsular invasion, multifocality, tumor size > 1 cm, and upper portion. The nomogram had good discrimination with a concordance index of 0.886 (95% confidence interval [CI], 0.823 to 0.948). In conclusion, the significant differences between skip metastasis and other types of LNM indicated that the lymph node drainage pathway of skip metastasis is different from either CLNM or LLNM. Furthermore, we established a nomogram for predicting risk of skip metastasis, which was able to effectively predict the potential risk of skip metastasis in patients without preoperative LNM clue.
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