Mangiola Stefano, Hong Matthew K H, Cmero Marek, Kurganovs Natalie, Ryan Andrew, Costello Anthony J, Corcoran Niall M, Macintyre Geoff, Hovens Christopher M
Departments of Urology and Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville 3050 Victoria, Australia.
Centre for Neural Engineering, 203 Bouverie St, Carlton 3053, Victoria, Australia.
Sci Rep. 2016 Sep 22;6:33918. doi: 10.1038/srep33918.
The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with metastases restricted to lymph nodes have a better prognosis than those with distant metastatic spread, suggesting the possibility of distinct aetiologies. To explore this, we traced patterns of cancer dissemination using tumour phylogenies inferred from genome-wide copy-number profiling of 48 samples across 3 patients with lymph node metastatic disease and 3 patients with osseous metastatic disease. Our results show that metastatic cells in regional lymph nodes originate from evolutionary advanced extraprostatic tumour cells rather than less advanced central tumour cell populations. In contrast, osseous metastases do not exhibit such a constrained developmental lineage, arising from either intra or extraprostatic tumour cell populations, at early and late stages in the evolution of the primary. Collectively, this comparison suggests that lymph node metastases may not be an intermediate developmental step for distant osseous metastases, but rather represent a distinct metastatic lineage.
淋巴结转移在远处前列腺癌扩散和致死率中的作用尚不明确。局限于淋巴结转移的患者比发生远处转移扩散的患者预后更好，这表明存在不同病因的可能性。为了探究这一点，我们利用肿瘤系统发育树追踪癌症扩散模式，该系统发育树是通过对3例淋巴结转移疾病患者和3例骨转移疾病患者的48个样本进行全基因组拷贝数分析推断得出的。我们的结果表明，区域淋巴结中的转移细胞起源于进化程度较高的前列腺外肿瘤细胞，而非进化程度较低的中央肿瘤细胞群体。相比之下，骨转移并不表现出这样受限的发育谱系，它可起源于前列腺内或前列腺外肿瘤细胞群体，在原发肿瘤演化的早期和晚期均可发生。总体而言，这种比较表明，淋巴结转移可能不是远处骨转移的中间发育步骤，而是代表一种独特的转移谱系。
