Hong Jian-Hua, Liang Sung-Tzu, Wang Alexander Sheng-Shin, Yeh Chia-Ming, Huang Hsiang-Po, Sun Chia-Dong, Zhang Zong-Han, Lu Shih-Yu, Chao Yen-Hsiang, Chen Chung-Hsin, Pu Yeong-Shiau
Department of Urology, National Taiwan University Hospital Taipei, Taiwan.
Institute of Biomedical Engineering, National Taiwan University Taipei, Taiwan.
Am J Cancer Res. 2022 Jul 15;12(7):3390-3404. eCollection 2022.
Although prostate cancer (PC) is the most common cancer among men in the Western world, there are no good biomarkers that can reliably differentiate between potentially aggressive and indolent PC. This leads to overtreatment, even for patients who can be managed conservatively. Previous studies have suggested that nuclear lamin proteins-especially lamin B1 (LMNB1)-play important roles in PC progression. However, the results of these studies are inconsistent. Here, we transfected the gene into the telomerase reverse transcriptase-immortalized benign prostatic epithelial cell line, EP156T to generate a LMNB1-overexpressing EP156T (LMN-EP156T) cell line with increased cellular proliferation. However, LMN-EP156T cells could neither form colonies in soft agar, nor establish subcutaneous growth or metastasis in the xenograft NOD/SCID mouse model. In addition, immunohistochemical staining of LMNB1 in PC specimens from 143 patients showed a statistically significant trend of stronger LMNB1 staining with higher Gleason scores. A univariate analysis of the clinicopathological parameters of 85 patients with PC who underwent radical prostatectomy revealed that pathological stage, resection margin, and extracapsular extension were significant predictors for biochemical recurrence (BCR). However, LMNB1 staining showed only a non-significant trend of association with BCR (high vs. low staining: hazard ratio (HR), 1.83; 95% confidence interval (CI), 0.98-3.41; = 0.059). In multivariate analysis, only pathological stage was a significant independent predictor of BCR (pT3 vs. pT2: HR, 2.29; 95% CI, 1.18-4.43; = 0.014). In summary, LMNB1 may play a role in the early steps of PC progression, and additional molecular alterations may be needed to confer full malignancy potential to initiated cells.
尽管前列腺癌(PC)是西方世界男性中最常见的癌症,但目前尚无能够可靠区分潜在侵袭性和惰性PC的良好生物标志物。这导致了过度治疗,即使是对于那些可以保守治疗的患者也是如此。先前的研究表明,核纤层蛋白——尤其是核纤层蛋白B1(LMNB1)——在PC进展中起重要作用。然而,这些研究的结果并不一致。在此,我们将该基因转染到端粒酶逆转录酶永生化的良性前列腺上皮细胞系EP156T中,以生成具有增强细胞增殖能力的LMNB1过表达EP156T(LMN-EP156T)细胞系。然而,LMN-EP156T细胞既不能在软琼脂中形成集落,也不能在异种移植NOD/SCID小鼠模型中建立皮下生长或转移。此外,对143例患者的PC标本进行LMNB1免疫组化染色显示,随着Gleason评分升高,LMNB1染色呈统计学显著增强趋势。对85例行根治性前列腺切除术的PC患者的临床病理参数进行单因素分析显示,病理分期、手术切缘和包膜外侵犯是生化复发(BCR)的重要预测因素。然而,LMNB1染色与BCR仅呈现非显著的关联趋势(高染色与低染色:风险比(HR),1.83;95%置信区间(CI),0.98 - 3.41;P = 0.059)。在多因素分析中,只有病理分期是BCR的显著独立预测因素(pT3与pT2:HR,2.29;95% CI,1.18 - 4.43;P = 0.014)。总之,LMNB1可能在PC进展的早期阶段起作用,并且可能需要额外的分子改变才能赋予起始细胞完全的恶性潜能。