Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Prostate. 2014 Apr;74(4):372-80. doi: 10.1002/pros.22758. Epub 2013 Dec 6.
Prostate cancer is the second leading cause of cancer-related death among men in North America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive cancers, which may lead to death. The current methods of detection include digital rectal examination and the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in aggressive prostate cancer.
In the current study, we assessed the diagnostic and prognostic potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy.
Using quantitative digital imaging software, we found that ACAT1 expression was significantly greater in cancerous cores compared to adjacent benign cores (P < 0.0001), in Gleason score (GS) ≥8 cancers versus GS≤6 cancers (P < 0.0001), GS≥8 cancers versus GS7 cancers (P = 0.001), as well as pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted biochemical recurrence in univariate (HR, 1.81, CI = 1.13-2.9, P = 0.0128), and multivariate models (HR, 1.69, CI = 1.01-2.81, P = 0.0431) including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases (P = 0.0025), whereas ERG positive cases did not display any differences.
Taken together, these findings indicate that ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in differentiating indolent and aggressive forms of cancer.
前列腺癌是北美男性癌症相关死亡的第二大主要原因。虽然大多数前列腺癌病例仍处于惰性状态，但有些患者的癌症会发展为侵袭性，这可能导致死亡。目前的检测方法包括直肠指检和血清 PSA 检测。然而，由于缺乏特异性，这两种方法都无法准确区分惰性和侵袭性癌症，因此需要额外的预后因素。之前，我们发现酮体途径的酶，特别是 ACAT1，在侵袭性前列腺癌中升高。
在本研究中，我们通过分析组织微阵列中 251 例接受根治性前列腺切除术的局限性前列腺癌患者的免疫组织化学表达，评估了 ACAT1 的诊断和预后潜力。
使用定量数字成像软件，我们发现与相邻良性核心相比，癌核心中的 ACAT1 表达明显更高（P < 0.0001），在 Gleason 评分（GS）≥8 与 GS≤6 癌症（P < 0.0001），GS≥8 与 GS7 癌症（P = 0.001），以及 pT3/pT4 与 pT2 癌症（P = 0.001）。此外，ACAT1 在单变量（HR，1.81，CI = 1.13-2.9，P = 0.0128）和多变量模型（HR，1.69，CI = 1.01-2.81，P = 0.0431）中预测了生化复发，包括术前 PSA 水平、Gleason 评分和病理分期。在单变量无复发生存分析中，ACAT1 表达预测了 ERG 阴性病例的复发（P = 0.0025），而 ERG 阳性病例则没有显示出任何差异。
总之，这些发现表明，ACAT1 表达可能成为前列腺癌的一个潜在预后标志物，特别是在区分惰性和侵袭性癌症方面。
