Androgen receptor and osteoglycin gene expression predicting prognosis of metastatic prostate cancer

Abstract

This study aimed to identify the predictive factors associated with the oncological outcomes of metastatic hormone-sensitive prostate cancer-related genes. A nomogram for predicting prostate cancer-specific survival (CSS) was constructed based on biopsy samples obtained from 103 patients with metastatic hormone-sensitive prostate cancer. We analyzed the association between clinical data and mRNA expression levels. The nomogram was externally validated in another cohort (n = 50) by using a concordance index. Based on the cutoff value, determined by a receiver operating characteristic analysis, longer CSS was observed in the high osteoglycin and androgen receptor expression level groups (> 1.133 and > 0.00; median CSS, 85.3 vs. 52.7 months, p = 0.045, and 69.1 vs. 32.1 months, p = 0.034, respectively), compared with that of the low expression level groups. The nomogram predicting CSS included hemoglobin (≥ 13.7 g/dL or < 13.7 g/dL), serum albumin (≥ 3.1 g/dL or < 3.1 g/dL), serum lactate dehydrogenase (≥ 222 IU/L or < 222 IU/L), total Japan Cancer of the Prostate Risk Assessment score, androgen receptor expression level, and osteoglycin expression level. The concordance indices for the internal and external validations were 0.664 and 0.798, respectively. In this study, a nomogram that integrated the expression levels of androgen receptors and osteoglycin to predict CSS in metastatic hormone-sensitive prostate cancer was established.

Fig. 1

Kaplan–Meier curves for prostate cancer-specific survival comparing high and low levels of androgen receptor (AR) and osteoglycin (OGN) expressions measured based on biopsy samples from 103 patients with metastatic hormone-sensitive prostate cancer. Patients with AR expression levels of > 0.00 or 0.00 (A) and those with OGN expression levels of > 1.133 or ≤ 1.133 (B) are compared.

Fig. 2

A nomogram predicting 1-year, 3-year, and 5-year cancer-specific survival among patients with metastatic hormone-sensitive prostate cancer (mHSPC) constructed based on 103 patients with mHSPC. AR, androgen receptor; J-CAPRA, Japan Cancer of the Prostate Risk Assessment; OGN, osteoglycin

Fig. 3

Immunohistochemical staining for androgen receptor (AR) (A) and osteoglycin (OGN) (B) in prostate cancer. Immunoreactivity for anti-AR antibody is identified in the nuclei of cancer cells and stromal cells. Immunoreactivity for anti-OGN antibody is observed in the cytoplasm of cancer cells (arrow) and stromal cells (arrowhead). The average Allred scores (A-score) determined by two pathologists (A) were 8 points for the nuclei of the cancer cells and 3 points for stromal cells. The total A-score was 11 points. The average A-scores determined by two pathologists (B) were 6.5 points for the cytoplasm of cancer cells and 6 points for stromal cells. The total A-score was 12.5 points. The median A-scores of AR in the nuclei of cancer cells and stromal cells were 6.5 (range, 0–8) and 3 (range, 0–5), respectively. The median A-scores of OGN in the cytoplasm of cancer cells and stromal cell were 2 (range, 0–7) and 4 (range, 0–8), respectively.

Fig. 4

Correlation between Allred score and expression levels of androgen receptor (A) and osteoglycin (B) using the Spearman rank-correlation coefficient.