Current biomarkers of invasive sporadic pituitary adenomas

Zheng, Xin; Li, Song; Zhang, Weihua; Zang, Zhenle; Hu, Jintao; Yang, Hui

doi:10.1016/j.ando.2016.02.004

Cited by 16 publications

(9 citation statements)

References 120 publications

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“…This inconsistency of data from different investigations is in line with a more general, apparent low reproducibility of the results of the research on invasion-related molecules. The results of most studies, including those with high-throughput methods, are not consistent with the other ones, as highlighted in recently published review articles [ 4 , 26 ]. This may reflect different methodological problems including patients' numbers, heterogeneity of patient groups, and differences between laboratory techniques.…”

Section: Discussionmentioning

confidence: 91%

The Search of miRNA Related to Invasive Growth of Nonfunctioning Gonadotropic Pituitary Tumors

Boresowicz

Kober

Rusetska

et al. 2020

International Journal of Endocrinology

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Purpose. Nonfunctioning gonadotropic pituitary neuroendocrine tumors (PitNETs) are among the most frequent neoplasms of pituitary gland. Although PitNETs are commonly considered benign, a notable part of patients suffer from tumor recurrence after treatment. Invasive growth of pituitary tumor is among the most important prognostic factors. Since molecular features of invasiveness are of potential clinical usefulness, this study was aimed to verify whether invasive and noninvasive nonfunctioning gonadotropic PitNETs differ in the miRNA expression profile and whether the differences could provide a possible molecular classifier. Methods. miRNA profiles were determined in 20 patients (11 invasive and 9 noninvasive tumors) using next-generation sequencing. The expression of selected miRNAs was assessed in the independent cohort of 80 patients with qRT-PCR. Results. When miRNA profiles of invasive and noninvasive tumors were compared, 29 miRNAs were found differentially expressed. Hsa-miR-184, hsa-miR-181a-2-3p, hsa-miR-93-3p, hsa-miR-574-5p, hsa-miR-185-5p, and hsa-miR-3200-5p showed a potential clinical value according to ROC curve analysis. Unfortunately, differential expression of only hsa-miR-185-5p was confirmed in the validation cohort, with AUG at 0.654. Conclusion. Differences in miRNAs expression profiles in invasive and noninvasive gonadotropic PitNETs are slight and the level of miRNA expression seems not to be applicable as useful classifier of tumor invasiveness.

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Section: Discussionmentioning

confidence: 91%

The Search of miRNA Related to Invasive Growth of Nonfunctioning Gonadotropic Pituitary Tumors

Boresowicz

Kober

Rusetska

et al. 2020

International Journal of Endocrinology

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“…Invasiveness of pituitary tumors is one of the most important prognostic features which is believed to be determined by tumor biology [ 5 ]. Our results show that invasive nonfunctioning gonadotroph PitNETs have lower LINE-1 methylation than noninvasive ones.…”

Section: Discussionmentioning

confidence: 99%

“…These data are concordant with findings from other human cancers where lower LINE-1 methylation is related to aggressive growth and worse prognosis [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. The molecular markers of nonfunctioning gonadotroph PitNET aggressive growth are needed as they could be useful in the clinical decision-making process [ 5 ]. Patients with rationally determined increased risk of recurrence could benefit from more individual treatment—more frequent follow-up visits or adjuvant therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Postmortem interval (PMI) for the samples was in the range of 25-46 h (median 35.5). According to previously reported data, this PMI does not affect DNA methylation assessment with bisulfite-based methods [5]. Three formalin-fixed, paraffin-embedded (FFPE) samples of histopathologically confirmed normal pituitaries obtained from resected Rathke's cleft cyst were used for immunohistochemical staining.…”

Section: Patients and Samplesmentioning

confidence: 94%

“…It is also one of the most important prognostic features for patients suffering from PitNETs [ 4 ]. Identification of biological determinants of aggressive growth of pituitary tumors could provide clinical benefit in regard to patient prognosis, adjuvant treatment and recommendation of more frequent follow-up visits for some patients [ 5 ]. Importantly, analysis of invasive and noninvasive nonfunctioning gonadotroph PitNETs revealed some differences in DNA methylation patterns [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive Elements

Rusetska

Kober

Król

et al. 2021

JCM

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Purpose: Epigenetic dysregulation plays a role in pituitary tumor pathogenesis. Some differences in DNA methylation were observed between invasive and noninvasive nonfunctioning gonadotroph tumors. This study sought to determine the role of DNA methylation changes in repetitive LINE-1 elements in nonfunctioning gonadotroph pituitary tumors. Methods: We investigated LINE-1 methylation levels in 80 tumors and normal pituitary glands with bisulfite-pyrosequencing. Expression of two LINE-1 open reading frames (L1-ORF1 and L1-ORF2) was analyzed with qRT-PCR in tumor samples and mouse gonadotroph pituitary cells treated with DNA methyltransferase inhibitor. Immunohistochemical staining against L1-ORF1p was also performed in normal pituitary glands and tumors. Results: Hypomethylation of LINE-1 was observed in pituitary tumors. Tumors characterized by invasive growth revealed lower LINE-1 methylation level than noninvasive ones. LINE-1 methylation correlated with overall DNA methylation assessed with HM450K arrays and negatively correlated with L1-ORF1 and L1-ORF2 expression. Treatment of αT3-1 gonadotroph cells with 5-Azacytidine clearly increased the level of L1-ORF1 and L1-ORF2 mRNA; however, its effect on LβT2 cells was less pronounced. Immunoreactivity against L1-ORF1p was higher in tumors than normal tissue. No difference in L1-ORF1p expression was observed in invasive and noninvasive tumors. Conclusion: Hypomethylation of LINE-1 is related to invasive growth and influences transcriptional activity of transposable elements.

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The use of mass spectrometry in a proteome‐centered multiomics study of human pituitary adenomas

Desiderio

Zhan

2021

Mass Spectrometry Reviews

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A pituitary adenoma (PA) is a common intracranial neoplasm, and is a complex, chronic, and whole-body disease with multicausing factors, multiprocesses, and multiconsequences. It is very difficult to clarify molecular mechanism and treat PAs from the single-factor strategy model. The rapid development of multiomics and systems biology changed the paradigms from a traditional single-factor strategy to a multiparameter systematic strategy for effective management of PAs.A series of molecular alterations at the genome, transcriptome, proteome, peptidome, metabolome, and radiome levels are involved in pituitary tumorigenesis, and mutually associate into a complex molecular network system. Also, the center of multiomics is moving from structural genomics to phenomics, including proteomics and metabolomics in the medical sciences. Mass spectrometry (MS) has been extensively used in phenomics studies of human PAs to clarify molecular mechanisms, and to discover biomarkers and therapeutic targets/drugs. MS-based

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Current biomarkers of invasive sporadic pituitary adenomas

Cited by 16 publications

References 120 publications

The Search of miRNA Related to Invasive Growth of Nonfunctioning Gonadotropic Pituitary Tumors

The Search of miRNA Related to Invasive Growth of Nonfunctioning Gonadotropic Pituitary Tumors

Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive Elements

The use of mass spectrometry in a proteome‐centered multiomics study of human pituitary adenomas

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