Verification of candidate microRNA markers for parathyroid carcinoma

PurposeParathyroid carcinoma (PCa) is a rare endocrine malignancy with poor prognosis and is often difficult to accurately diagnose both before and after surgery. Dysregulated microRNA (miRNA) levels have been identified in PCa using a limited number of samples. The aim of the present study was to verify a group of miRNA markers in a new series of samples to explore their potential significance in PCa diagnosis.MethodsA total of 58 tissue samples, including 17 PCa lesions and 41 sporadic parathyroid adenomas (PAds), were obtained from 56 primary hyperparathyroidism (pHPT) patients. Candidate miRNAs (miR-139-5p, miR-155-5p, miR-222-3p, miR-26b-5p, miR-296-5p, miR-30b-5p, miR-372-3p, miR-503-5p, miR-517c-3p, miR-7-5p, and miR-126-5p) were quantified by TaqMan real-time quantitative PCR assays.ResultsUp-regulated miR-222 (p = 0.041) levels and down-regulated miR-139 (p = 0.003), miR-30b (p < 0.001), miR-517c (p = 0.038), and miR-126* (p = 0.002) levels were found in PCa relative to PAd. Binary logistic regression analysis showed that miR-139 and miR-30b were the best diagnostic markers. The combination of miR-139 and miR-30b yielded an area under the receiver operating characteristic curve of 0.888. Additionally, serum calcium (rs = −0.518, p < 0.001), intact parathyroid hormone (iPTH) (rs = −0.495, p < 0.001), and alkaline phosphatase (ALP) (rs = −0.523, p < 0.001) levels were negatively correlated with miR-30b levels.ConclusionsmiR-139, miR-222, miR-30b, miR-517c, and miR-126* were differentially expressed between PCa and PAd. The combined analysis of miR-139 and miR-30b may be used as a potential diagnostic strategy for distinguishing PCa from PAd.

[1]  L. Tian,et al.  The molecular mechanisms and therapeutic potential of microRNA-7 in cancer , 2015, Expert opinion on therapeutic targets.

[2]  Thomas D. Schmittgen,et al.  Analyzing real-time PCR data by the comparative CT method , 2008, Nature Protocols.

[3]  P. Leedman,et al.  MicroRNA-7: A miRNA with expanding roles in development and disease. , 2015, International Journal of Biochemistry and Cell Biology.

[4]  N. Kumari,et al.  Molecular Characteristics of Large Parathyroid Adenomas , 2016, World Journal of Surgery.

[5]  Nils Lid Hjort,et al.  Goodness‐of‐fit processes for logistic regression: simulation results , 2002, Statistics in medicine.

[6]  V. Vaira,et al.  MicroRNA deregulation in parathyroid tumours suggests an embryonic signature , 2015, Journal of Endocrinological Investigation.

[7]  E. Kebebew,et al.  Identification of Differentially Expressed MicroRNA in Parathyroid Tumors , 2011, Annals of Surgical Oncology.

[8]  Guanghua Chen,et al.  Identification of serum miR-139-3p as a non-invasive biomarker for colorectal cancer , 2017, Oncotarget.

[9]  S. Corbetta,et al.  Epigenetic Alterations in Parathyroid Cancers , 2017, International journal of molecular sciences.

[10]  Qizhan Liu,et al.  NF-kB-regulated exosomal miR-155 promotes the inflammation associated with arsenite carcinogenesis. , 2017, Cancer letters.

[11]  Jun Shen,et al.  Circular RNA participates in the carcinogenesis and the malignant behavior of cancer , 2017, RNA biology.

[12]  J. Carpten,et al.  HRPT2, encoding parafibromin, is mutated in hyperparathyroidism–jaw tumor syndrome , 2002, Nature Genetics.

[13]  R. Lloyd,et al.  WHO classification of tumours of endocrine organs , 2017 .

[14]  Xiaofeng Cui,et al.  Tumor Suppressor PTPRJ Is a Target of miR‐155 in Colorectal Cancer , 2017, Journal of cellular biochemistry.

[15]  C. Marcocci,et al.  Epidemiology, pathogenesis of primary hyperparathyroidism: Current data. , 2015, Annales d'endocrinologie.

[16]  M. Rugge,et al.  CDC73 mutational status and loss of parafibromin in the outcome of parathyroid cancer , 2013, Endocrine connections.

[17]  Yan Wang,et al.  MiR-30b-5p functions as a tumor suppressor in cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit α-13 in renal cell carcinoma. , 2017, Gene.

[18]  F. Cetani,et al.  The microRNA cluster C19MC is deregulated in parathyroid tumours. , 2012, Journal of molecular endocrinology.

[19]  V. Vaira,et al.  MicroRNAs in parathyroid physiopathology , 2017, Molecular and Cellular Endocrinology.

[20]  J. Chen,et al.  MiR-30b-5p acts as a tumor suppressor, repressing cell proliferation and cell cycle in human hepatocellular carcinoma. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[21]  N. Perrier,et al.  Epigenetic processes in sporadic parathyroid neoplasms , 2017, Molecular and Cellular Endocrinology.

[22]  C. Marcocci,et al.  Update on parathyroid carcinoma , 2016, Journal of Endocrinological Investigation.

[23]  G. Reid,et al.  microRNA-7 as a tumor suppressor and novel therapeutic for adrenocortical carcinoma , 2015, Oncotarget.

[24]  A. Godwin,et al.  Role of miR-139 as a surrogate marker for tumor aggression in breast cancer. , 2017, Human pathology.

[25]  C. Croce,et al.  MicroRNAs in Cancer. , 2009, Annual review of medicine.

[26]  E. Schadt,et al.  Genomic profiling reveals mutational landscape in parathyroid carcinomas. , 2017, JCI insight.

[27]  G. Westin Molecular genetics and epigenetics of nonfamilial (sporadic) parathyroid tumours , 2016, Journal of internal medicine.

[28]  J. Silver,et al.  Parathyroid‐specific deletion of dicer‐dependent microRNAs abrogates the response of the parathyroid to acute and chronic hypocalcemia and uremia , 2015, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[29]  M. Bisceglia,et al.  Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue. , 2010, Endocrine-related cancer.

[30]  N. Bhowmick,et al.  MicroRNA applications for prostate, ovarian and breast cancer in the era of precision medicine , 2017, Endocrine-related cancer.

[31]  K. Schulte,et al.  Diagnosis and management of parathyroid cancer , 2012, Nature Reviews Endocrinology.

[32]  Xuan Liang,et al.  MicroRNA‐155‐5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway , 2017, Cancer science.

[33]  K. Gopinath,et al.  Oncogenic MicroRNA-155 Down-regulates Tumor Suppressor CDC73 and Promotes Oral Squamous Cell Carcinoma Cell Proliferation , 2012, The Journal of Biological Chemistry.

[34]  M. Dowsett,et al.  miR-155 Drives Metabolic Reprogramming of ER+ Breast Cancer Cells Following Long-Term Estrogen Deprivation and Predicts Clinical Response to Aromatase Inhibitors. , 2016, Cancer research.

[35]  M. Nie,et al.  Novel HRPT2/CDC73 Gene Mutations and Loss of Expression of Parafibromin in Chinese Patients with Clinically Sporadic Parathyroid Carcinomas , 2012, PloS one.

[36]  W. Simonds,et al.  Parathyroid cancer. , 2010, Seminars in oncology.

[37]  J. Kjems,et al.  Circular RNA and miR-7 in cancer. , 2013, Cancer research.

[38]  Kai Wang,et al.  MiR‐139‐5p inhibits the tumorigenesis and progression of oral squamous carcinoma cells by targeting HOXA9 , 2017, Journal of cellular and molecular medicine.