Radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy with or without chemotherapy: Development of a nomogram based on the equivalent dose.

OBJECTIVE: The aim of this study was to establish a nomogram for predicting radiation-induced hypothyroidism (RHT) based on an equivalent dose at 2 Gy per fraction (EQD2) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) with or without chemotherapy. METHODS: Two hundred forty-four eligible patients with NPC were recruited for this study. Patients' clinical factors and dose-volume parameters of the thyroid gland were retrieved from medical records and the IMRT treatment planning system, respectively. The irradiation doses were converted into EQD2 for analysis. Least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate logistic regression analysis were performed to identify optimal predictors of RHT for constructing the nomogram. RESULTS: With a median follow-up of 63.0 months, the cumulative incidence rates of RHT at 3 months and 1-, 2-, 3-, 4- and 5- year after IMRT were 10.2%, 36.2%, 47.6%, 54.2%, 58.8% and 69.4%, respectively. Four independent factors for predicting RHT, including gender, age, pretreatment volume of the thyroid gland and V35Gy(3Gy) of the thyroid gland, were identified and incorporated into the nomogram. The area under the ROC curve of the nomogram was 0.747 (95% confidence interval 0.685 - 0.809). Calibration curves and DCA curves showed that the nomogram was in good agreement with the actual observations and clinical usefulness. CONCLUSIONS: The nomogram proposed in this study provides a reliable estimate of RHT risk in patients with NPC after IMRT and appears to have the potential to be a useful tool for widespread clinical applications.

Long non-coding RNA LINC01503 promotes the progression of hepatocellular carcinoma via activating MAPK/ERK pathway.

Background: Increasing evidence has implicated that lncRNAs (long non-coding RNAs) play significant roles in carcinogenesis and progression of HCC (hepatocellular carcinoma). LINC01503 is a new lncRNA related to several tumors. Nonetheless, its role in HCC still remains unclear. Methods: The expression levels of LINC01503 in HCC, normal liver tissues as well as HCC cell lines were evaluated by TCGA (The Cancer Genome Atlas) and real-time PCR assay, respectively. The relationship between LINC01503 levels and the prognosis of patients with HCC was evaluated using Kaplan-Meier survival analysis. Then the potential biological functions and pathways related to LINC01503 were investigated by GO (Gene Ontology) analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, and GSEA v4.0.1 software was employed. Furthermore, the influence of LINC01503 on the proliferation and apoptosis of HCC cells was confirmed using CCK8 assay, flow cytometry, and clone formation assay in cell experiments. Also the pro-tumor effect of LINC01503 was verified by mice xenograft experiment in vivo. In addition, the functional pathway of LINC01503 was proved by western blot and rescue experiments. Results: LINC01503 was highly expressed in HCC and positively correlated with large tumor size, high tumor grade, advanced tumor stage, and poor prognosis of HCC patients. Silencing LINC01503 with shRNA significantly restrained the proliferation of MHCC-97H HCC cells and strengthened the apoptosis, while up-regulation of LINC01503 in Huh7 HCC cells contributed to the contrary effects. Besides, LINC01503 promoted tumor growth of nude mice transplanted with liver cancer cells. Mechanistically, MAPK/ERK signaling pathway was activated by LINC01503, inhibition of which could alleviate the pro-tumor effect of LINC01503, consistent with the forecast of GSEA (Gene Set Enrichment Analysis). Conclusion: LINC01503 is highly expressed in HCC and promotes the progression of HCC via MAPK/ERK pathway, which maybe a new potential biomarker and therapeutic target for HCC.