Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Office K4/436 CSC-8550, 600 Highland Avenue, Madison, WI, 53792-8550, USA.
Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Endocr Pathol. 2019 Mar;30(1):56-63. doi: 10.1007/s12022-018-9564-1.
Recent studies suggest onco-regulatory roles for two long non-coding RNAs (lncRNAs), MALAT1 and HOTAIR, in various malignancies; however, these lncRNAs have not been previously examined in neuroendocrine neoplasms (NENs) of gastroenteropancreatic origins (GEP-NENs). In this study, we evaluated the expressions and prognostic significance of MALAT1 and HOTAIR in 83 cases of GEP-NENs (60 grade 1, 17 grade 2, and 6 grade 3 tumors) diagnosed during the years 2005-2017. Expression levels of MALAT1 and HOTAIR were digitally quantitated in assembled tissue microarray slides labeled by chromogenic in situ hybridization (ISH) using InForm 1.4.0 software. We found diffuse nuclear expression of both HOTAIR and MALAT1 in all primary tumors of GEP-NENs with variable intensities. By multivariate model which adjusted for age and histologic grade, high expression of HOTAIR was associated with lower presenting T and M stages and subsequent development of metastases (P < 0.05). MALAT1 expression was associated with presenting T stage and development of metastases (P < 0.05). In summary, MALAT1 and HOTAIR are commonly expressed in GEP-NENs. High expression of either lncRNA showed grade-independent associations with clinically less aggressive disease.
最近的研究表明，两种长链非编码 RNA（lncRNA）——MALAT1 和 HOTAIR——在各种恶性肿瘤中具有肿瘤调节作用；然而，这些 lncRNA 以前并未在胃肠胰神经内分泌肿瘤（GEP-NEN）中进行过研究。在这项研究中，我们评估了 MALAT1 和 HOTAIR 在 83 例 GEP-NEN（2005-2017 年诊断的 60 级 1 例、17 级 2 例和 6 级 3 例肿瘤）中的表达和预后意义。使用 InForm 1.4.0 软件，通过显色原位杂交（ISH）标记的组织微阵列载玻片对 MALAT1 和 HOTAIR 的表达水平进行数字定量。我们发现，所有 GEP-NEN 的原发肿瘤均表现出 HOTAIR 和 MALAT1 的弥漫性核表达，其强度不同。通过多变量模型，调整年龄和组织学分级，HOTAIR 的高表达与较低的 T 和 M 分期以及随后的转移发展相关（P<0.05）。MALAT1 表达与 T 分期和转移的发展相关（P<0.05）。总之，MALAT1 和 HOTAIR 在 GEP-NEN 中普遍表达。这两种 lncRNA 的高表达与临床侵袭性较低的疾病无关。
