Background

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at post-transcriptional level, having a role in many biological processes, such as control of cell proliferation, cell cycle, and cell death. Altered miRNA expression has been reported in many neoplasms, including pituitary adenomas (PAs).

Purpose

In this study, we aimed to evaluate the expression of 20 miRNAs involved in pathways relevant to pituitary pathophysiology, in PAs and normal pituitary tissue and to correlate their expression profile with clinical and pathological features.

Methods

Pituitary tumor samples were obtained during transphenoidal surgery from patients with non-functioning (NFPA, n = 12) and functioning (n = 11, 5 GH-, 3 ACTH-, 3 PRL-omas) PAs. The expression of selected miRNAs in PAs and in normal pituitary was analyzed by RT-qPCR. miRNAs expression was correlated with demographic, clinical, and neuroradiological data and with histopathological features including pituitary hormones immunostaining, Ki-67 proliferation index, and p53 immunohistochemistry evaluation.

Results

All evaluated miRNAs except miR-711 were expressed in both normal and tumor pituitary tissue. Seventeen miRNAs were significantly down-regulated in pituitary tumors compared to normal pituitary. miRNAs were differentially expressed in functioning PAs or in NFPAs, as in the latter group miR-149-3p (p = 0.036), miR-130a-3p (p = 0.014), and miR-370-3p (p = 0.026) were significantly under expressed as compared to functioning tumors. Point-biserial correlation analysis demonstrated a negative correlation between miR-26b-5p and Ki-67 (p = 0.031) and between miR-30a-5p and ‘atypical’ morphological features (p = 0.038) or cavernous sinus invasion (p = 0.049), while 508-5p was inversely correlated with clinical aggressiveness (p = 0.043).

Conclusions

In this study, we found a significant down-regulation of 17 miRNAs in PAs vs normal pituitary, with differential expression profile related to functional status and tumor aggressiveness.

中文翻译：

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垂体肿瘤中MicroRNA的表达：与功能状态，病理特征和临床行为有关的差异。

背景

微小RNA（miRNA）是小的非编码RNA分子，可在转录后水平调节基因表达，在许多生物学过程中发挥作用，例如控制细胞增殖，细胞周期和细胞死亡。在许多肿瘤，包括垂体腺瘤（PAs）中，已经报道了改变的miRNA表达。

目的

在这项研究中，我们旨在评估与垂体病理生理相关的途径，PA和正常垂体组织中20种miRNA的表达，并将其表达谱与临床和病理特征相关联。

方法

垂体肿瘤样品是在经蝶骨手术期间从功能异常（NFPA，n  = 12）和功能 异常（n = 11，5 GH-，3 ACTH-，3 PRL-omas）的患者获得的。通过RT-qPCR分析选定的miRNA在PAs和正常垂体中的表达。miRNA的表达与人口统计学，临床和神经放射学数据以及组织病理学特征（包括垂体激素免疫染色，Ki-67增殖指数和p53免疫组化评估）相关。

结果

除miR-711外，所有评估的miRNA均在正常和肿瘤垂体组织中表达。与正常垂体相比，垂体肿瘤中有17种miRNA显着下调。miRNA在功能性PA或NFPA中差异表达，如后者的miR-149-3p（p  = 0.036），miR-130a-3p（p  = 0.014）和miR-370-3p（p  = 0.026）与功能性肿瘤相比，表达明显不足。点-双序列相关分析表明，miR-26b-5p和Ki-67之间呈负相关（p  = 0.031），miR-30a-5p与'非典型'形态特征（p  = 0.038）或海绵窦浸润（p = 0.049），而508-5p与临床攻击性呈负相关（p  = 0.043）。

结论

在这项研究中，我们发现PAs中的17个miRNA与正常的垂体相比显着下调，其差异表达谱与功能状态和肿瘤侵袭性有关。