Overexpression of MiR-155-5p and increased number of macrophage population in precancerous prostatic disease

Latar Belakang: Gangguan regulasi mikroRNA(miR) dan inflamasi kronik dapat mengubah tumor menjadi karsinoma dan kanker dengan metastasis melalui perubahan seluler dan genomik. Lesi prekanker memiliki peluang 33,3 persen menjadi kanker. Penelitian ini bertujuan untuk mengkaji peran miR-155-5p terhadap mRNA SOCS1 dan populasi makrofag terhadap progresivitas penyakit yang berhubungan dengan Benign Prostate Hyperplasia (BPH), High Grade Prostatic Intraepithelial Neoplasia (HGPIN), dan Prostate Adenocarcinoma (PRAD). Metode: Penelitian ini merupakan penelitian potong lintang dengan 3 kelompok, yaitu BPH,HGPIN, dan PRAD. Sampel jaringan didapatkan dari Tindakan TURP. Ekspresi miR-155 dianalisis menggunakan qPCR dan dikalkulasi menggunakan metode Livak. Ekspresi mRNA SOCS-1 dianalisis menggunakan reverse transcriptase PCR. Penanda pan makrofag, anti CD-68 monoclonal antibody(MoAb) digunakan untuk mendeteksi populasi makrofag pada jaringan dengan imunohistokimia. Hasil: Ekspresi miR-155 lebih tinggi pada HGPIN dibandingkan BPH dan PRAD (p=0,14). Ekspresi mRNA SOCS1 pada HGPIN paling rendah diantara ketiga sampel (p=0,96). Terdapat korelasi negative antara miR-155 dan mRNA SOCS1 (p=0,02). Terdapat peningkatan persentase populasi makrofag yang signifikan pada HGPIN (6,03 persen) dibandingkan BPH (0.89 persen) dengan p=0,00. Kesimpulan: Pada penelitian ini, terdapat perubahan persentase makrofag dan miR-155 pada HGPIN. Variasi ekspresi miR-155 dan persentase populasi makrofag dapat disebabkan karena perubahan epigenetik. Oleh sebab itu, perlu penelitian lebih lanjut untuk memvalidasi hasil tersebut dan memahami kemungkinan menjadi biomarker pada penyakit prekanker pada prostat. Kata Kunci: Prostatic Intaepithelial Neoplasia, miR-155, Makrofag Abstract Background: Impaired microRNA(miR) regulation and chronic inflammation could transform tumors into carcinoma and cancer by metastasis through cellular and genomic changes. Precancerous lesions have a 33.3 percent chance of becoming cancerous. This study investigated the role of miR-155 related to SOCS1 mRNA and macrophage population in disease progression associated with Benign Prostate Hyperplasia (BPH), High-Grade Prostatic Intraepithelial Neoplasia (HGPIN), and Prostate Adenocarcinoma (PRAD). Methods: This was a cross-sectional study using three groups of samples, namely BPH, HGPIN, and PRAD. Tissue samples were obtained from TURP Action. The expression of miR-155 was analyzed using real-time qPCR and calculated using the Livak method. The expression of SOCS1 mRNA was analyzed using reverse transcriptase PCR. The macrophage pan-marker, anti-CD68 monoclonal antibody (MoAb), was used to detect macrophage population in tissues by immunohistochemistry. Results: The expression of miR-155 was higher in HGPIN than BPH and PRAD (p=0.14). The expression of SOCS1 mRNA in HGPIN was the lowest among the three samples (p=0.96). There was a negative correlation between miR-155 and SOCS1 mRNA (p=0.02). There was a significant increase in the percentage of the macrophage population in HGPIN (6.03 percent) compared to BPH (0.89 percent) with p=0.00. Conclusion: In this study, there were changes in the percentage of macrophage and miR-155 in HGPIN. The variation in miR-155 expression and the percentage of the macrophage may be caused by epigenetic changes. Therefore, further research is needed to validate these results and understand the possibility of being a biomarker in precancerous disease of the prostate. Keywords: Prostatic Intraepithelial Neoplasia, miR-155, Macrophage

Download Full-text

Plasma Sarcosine Measured by Gas Chromatography-Mass Spectrometry Distinguishes Prostatic Intraepithelial Neoplasia and Prostate Cancer from Benign Prostate Hyperplasia

Laboratory Medicine ◽

10.1093/labmed/lmaa008 ◽

2020 ◽

Vol 51 (6) ◽

pp. 566-573 ◽

Cited By ~ 2

Author(s):

Pavel A Markin ◽

Alex Brito ◽

Natalia Moskaleva ◽

Miguel Fodor ◽

Ekaterina V Lartsova ◽

...

Keyword(s):

Prostate Cancer ◽

Mass Spectrometry ◽

Gas Chromatography ◽

Diagnostic Accuracy ◽

Benign Prostate Hyperplasia ◽

Intraepithelial Neoplasia ◽

Prostatic Intraepithelial Neoplasia ◽

Gas Chromatography Mass Spectrometry ◽

Prostate Hyperplasia ◽

Benign Prostate

Abstract Objective Sarcosine was postulated in 2009 as a biomarker for prostate cancer (PCa). Here, we assess plasma sarcosine as a biomarker that is complementary to prostate-specific antigen (PSA). Methods Plasma sarcosine was measured using gas chromatography-mass spectrometry (GC-MS) in adults classified as noncancerous controls (with benign prostate hyperplasia [BPH], n = 36), with prostatic intraepithelial neoplasia (PIN, n = 16), or with PCa (n = 27). Diagnostic accuracy was assessed using receiver operating characteristic curve analysis. Results Plasma sarcosine levels were higher in the PCa (2.0 µM [1.3–3.3 µM], P <.01) and the PIN (1.9 µM [1.2–6.5 µM], P <.001) groups than in the BPH (0.9 µM [0.6–1.4 µM]) group. Plasma sarcosine had “good” and “very good” discriminative capability to detect PIN (area under the curve [AUC], 0.734) and PCa (AUC, 0.833) versus BPH, respectively. The use of PSA and sarcosine together improved the overall diagnostic accuracy to detect PIN and PCa versus BPH. Conclusion Plasma sarcosine measured by GC-MS had “good” and “very good” classification performance for distinguishing PIN and PCa, respectively, relative to noncancerous patients diagnosed with BPH.

Download Full-text