Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.
Endocr Relat Cancer. 2018 Apr;25(4):407-420. doi: 10.1530/ERC-17-0470.
The clinical presentation of primary hyperparathyroidism (PHPT) varies widely, although the underlying mechanistic reasons for this disparity remain unknown. We recently reported that parathyroid tumors can be functionally segregated into two distinct groups on the basis of their relative responsiveness to ambient calcium, and that patients in these groups differ significantly in their likelihood of manifesting bone disability. To examine the molecular basis for this phenotypic variation in PHPT, we compared the global gene expression profiles of calcium-sensitive and calcium-resistant parathyroid tumors. RNAseq and proteomic analysis identified a candidate set of differentially expressed genes highly correlated with calcium-sensing capacity. Subsequent quantitative assessment of the expression levels of these genes in an independent cohort of parathyroid tumors confirmed that calcium-sensitive tumors cluster in a discrete transcriptional profile group. These data indicate that PHPT is not an etiologically monolithic disorder and suggest that divergent molecular mechanisms could drive the observed phenotypic differences in PHPT disease course, provenance, and outcome.
原发性甲状旁腺功能亢进症（PHPT）的临床表现差异很大，尽管这种差异的潜在机制原因尚不清楚。我们最近报道称，甲状旁腺瘤可以根据其对环境钙的相对反应性，在功能上分为两个不同的组，而这两组患者出现骨功能障碍的可能性有显著差异。为了研究 PHPT 中这种表型变异的分子基础，我们比较了钙敏感和钙抵抗性甲状旁腺瘤的全基因组表达谱。RNAseq 和蛋白质组学分析确定了一组候选差异表达基因，这些基因与钙感应能力高度相关。随后在另一批甲状旁腺瘤的独立队列中对这些基因的表达水平进行定量评估，证实钙敏感型肿瘤聚集在一个离散的转录谱群中。这些数据表明 PHPT 不是一种病因单一的疾病，并且表明不同的分子机制可能导致 PHPT 疾病过程、来源和结果中观察到的表型差异。
