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Lower PRDM2 expression is associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

ABSTRACT: Dopamine agonists (DAs) are the first-line treatment for prolactinomas, which account for 25-30% of functioning pituitary adenomas, and bromocriptine (BRC) is the only commercially available DAs in China. However, tumors are resistant to therapy in 5-18% of patients.The exomes of six responsive prolactinomas and six resistant prolactinomas were analyzed by whole-exome sequencing.Using stringent variant calling and filtering parameters, ten somatic variants that were mainly associated with DNA repair or protein metabolic processes were identified. New resistant variants were identified in multiple genes including PRDM2, PRG4, MUC4, DSPP, DPCR1, RP1L1, MX2, POTEF, C1orf170, and KRTAP10-3. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT-qPCR) in 12 prolactinomas and 3 normal pituitary glands. The mRNA levels of PRDM2 were approximately five-fold lower in resistant prolactinomas than in responsive tumors (p?

SUBMITTER: Gao H

PROVIDER: S-EPMC4407330 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Lower PRDM2 expression is associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

Gao Hua H Wang Fei F Lan Xiaolei X Li Chuzhong C Feng Jie J Bai Jiwei J Cao Lei L Gui Songbai S Hong Lichuan L Zhang Yazhuo Y

BMC cancer 20150412

<h4>Background</h4>Dopamine agonists (DAs) are the first-line treatment for prolactinomas, which account for 25-30% of functioning pituitary adenomas, and bromocriptine (BRC) is the only commercially available DAs in China. However, tumors are resistant to therapy in 5-18% of patients.<h4>Methods</h4>The exomes of six responsive prolactinomas and six resistant prolactinomas were analyzed by whole-exome sequencing.<h4>Results</h4>Using stringent variant calling and filtering parameters, ten somat ...[more]

PMID: 25884948

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Project description:BackgroundMany studies have reported the presence of Positive Regulatory/Su(var)3-9, Enhancer-of-zeste and Trithorax Domain 2 (PRDM2) downregulation in cancer. However, its potential as a diagnostic biomarker is still unclear. Hence, a systematic review and meta-analysis were conducted to address this issue.IntroductionAs of 2018, cancer has become the second leading cause of death worldwide. Thus, cancer control is exceptionally vital in reducing mortality. One such example is through early diagnosis of cancer using tumor biomarkers. Having a function as a tumor suppressor gene (TSG), PRDM2 has been linked with carcinogenesis in several solid tumor. This study aims to assess the relationship between PRDM2 downregulation and solid tumor, its relationship with clinicopathological data, and its potential as a diagnostic biomarker. This study also aims to evaluate the quality of the studies, data reliability and confidence in cumulative evidence.Materials & methodsA protocol of this study is registered at the International Prospective Register of Systematic Reviews (PROSPERO) with the following registration number: CRD42019132156. PRISMA was used as a guideline to conduct this review. A comprehensive electronic search was performed from inception to June 2019 in Pubmed, Cochrane Library, ProQuest, EBSCO and ScienceDirect. Studies were screened and included studies were identified based on the criteria made. Finally, data synthesis and quality assessment were conducted.ResultsThere is a significant relationship between PRDM2 downregulation with solid tumor (RR 4.29, 95% CI [2.58-7.13], P < 0.00001). The overall sensitivity and specificity of PRDM2 downregulation in solid tumors is 84% (95% CI [39-98%]) and 86% (95% CI [71-94%]), respectively. There is a low risk of bias for the studies used. TSA results suggested the presence of marked imprecision. The overall quality of evidence for this study is very low.DiscussionWe present the first meta-analysis that investigated the potential of PRDM2 downregulation as a diagnostic biomarker in solid tumor. In line with previous studies, our results demonstrated that PRDM2 downregulation occurs in solid tumor. A major source of limitation in this study is the small number of studies.ConclusionsOur review suggested that PRDM2 is downregulated in solid tumor. The relationship between PRDM2 downregulation and clinicopathological data is still inconclusive. Although the sensitivity and specificity of PRDM2 downregulation are imprecise, its high values, in addition to the evidence that suggested PRDM2 downregulation in solid tumor, hinted that it might still have a potential to be used as a diagnostic biomarker. In order to further strengthen these findings, more research regarding PRDM2 in solid tumors are encouraged.

Dataset Information

Lower PRDM2 expression is associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

Publications

Lower PRDM2 expression is associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

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