Mishra Alok, Shrivastava Ashutosh
Center for Advance Research, King George's Medical University, Lucknow, Uttar Pradesh, India.
Int J Appl Basic Med Res. 2020 Jan-Mar;10(1):43-48. doi: 10.4103/ijabmr.IJABMR_287_19. Epub 2020 Jan 3.
Thyroid hormones (THs) are critically important for development, homeostasis, and metabolic regulation in mammals. Iodine, one of the constituents of TH, is actively supplied by sodium iodide symporter (NIS) into the thyroid gland. TH is subsequently transported to distant organs where its activation and deactivation is catalyzed by isoforms of deiodinases (DIOs). NIS protein has been known to overexpress in cancer cases of the breast and gastrointestinal organs. Recent studies show a possible role of DIOs in various cancers.
In the present investigation, the prognostic significance of NIS and DIO-1, 2 and 3 was studied in gastric cancer using a data mining bioinformatic approach.
"The Kaplan-Meier plotter" database was used for direct validation in clinically relevant 876 gastric cancer patients with >15 years of follow-up information. After obtaining KM survival plots, hazard ratio and log-rank value were calculated.
Increased expression of NIS and DIO 1-3 is significantly associated with worsen overall survival of gastric cancer patients followed for 20 years. Prognostic roles of NIS and individual DIOs were assessed in different types of gastric cancer classified based on morphologies, human epidermal growth factor receptor-2 receptor status, treatment choices, and different clinicopathological features.
Based on these analyses, the present study found the indication of prognostic values of these genes. This information will contribute to better understanding of managing complex and heterogeneous gastric cancer. Further, these findings may be beneficial as a companion diagnostic tool predicting more accurate gastric cancer prognosis.
甲状腺激素(THs)对哺乳动物的发育、体内平衡和代谢调节至关重要。碘是TH的组成成分之一,通过碘化钠同向转运体(NIS)被主动转运至甲状腺。随后,TH被转运至远处器官,在那里其激活和失活由脱碘酶(DIOs)的同工型催化。已知NIS蛋白在乳腺癌和胃肠道器官的癌症病例中过表达。最近的研究表明DIOs在各种癌症中可能发挥作用。
在本研究中,使用数据挖掘生物信息学方法研究了NIS和DIO-1、2及3在胃癌中的预后意义。
“Kaplan-Meier绘图仪”数据库用于对876例有超过15年随访信息的临床相关胃癌患者进行直接验证。获得KM生存曲线后,计算风险比和对数秩值。
NIS和DIO 1-3表达增加与随访20年的胃癌患者总体生存率恶化显著相关。在根据形态学、人表皮生长因子受体2受体状态、治疗选择和不同临床病理特征分类的不同类型胃癌中评估了NIS和单个DIO的预后作用。
基于这些分析,本研究发现了这些基因具有预后价值的迹象。这些信息将有助于更好地理解复杂和异质性胃癌的管理。此外,这些发现作为预测更准确胃癌预后的伴随诊断工具可能是有益的。