Lan Ruoxin, Zhang Kun, Niu Tianhua, You Zongbing
Department of Structural & Cellular Biology, Tulane University New Orleans, LA, USA.
Department of Computer Science and Biostatistics Facility of RCMI Cancer Research Center, Xavier University of Louisiana New Orleans, LA, USA.
Am J Clin Exp Urol. 2019 Dec 15;7(6):352-377. eCollection 2019.
Interleukin-17 () has been shown to promote development of hormone-naïve prostate cancer (HNPC) and castration-resistant prostate cancer (CRPC) as well as lymph node metastasis in mouse models. Gene alterations of family of cytokines and their downstream genes in human prostate cancer have not been investigated. We studied 7 datasets archived in cBioPortal and queried gene alterations in a total of 1303 cases of human prostate cancers. 35 genes were examined, including family of cytokines and receptors, -downstream genes, and genes related to -downstream genes. We found that 34/35 (97%) genes had significantly more alterations in metastatic prostate cancer (with alteration rates ranging from 3.42% to 13.01%) than primary prostate cancer (with alteration rates ranging from 0.40% to 2.96%). 15/35 (43%) genes had significantly more alterations in primary CRPC than primary HNPC. 34/35 (97%) genes had significantly more alterations in metastatic CRPC than primary HNPC. Only three genes (, and ) had significantly more alterations in metastatic CRPC than primary CRPC. The gene alterations were mostly gene amplifications (97%), while gene deep deletions, missense mutations, and truncating mutations were very rare. 7/35 (20%) genes had significantly more alterations in primary neuroendocrine prostate cancer (NEPC) than primary adenocarcinoma (AC). 23/35 (66%) genes had significantly more alterations in metastatic NEPC than metastatic AC. Only three genes (, and ) had significantly more alterations in metastatic NEPC than metastatic AC with neuroendocrine features. Most of the gene alterations in metastatic NEPC were gene amplifications (80%), while gene deep deletions, missense mutations, and truncating mutations were very rare. Our findings suggest that gene amplifications of and related genes are more frequently found in metastatic CRPC and NEPC than primary hormone-naïve prostate adenocarcinomas, implying that and related genes may play important roles in the progression from HNPC to CRPC and from primary location to metastasis as well as in development of metastatic NEPC.
白细胞介素-17（IL-17）已被证明在小鼠模型中可促进激素未治疗的前列腺癌（HNPC）和去势抵抗性前列腺癌（CRPC）的发展以及淋巴结转移。人类前列腺癌中细胞因子家族及其下游基因的基因改变尚未得到研究。我们研究了存档于cBioPortal中的7个数据集，并查询了总共1303例人类前列腺癌的基因改变情况。检测了35个基因，包括细胞因子家族及其受体、IL-17下游基因以及与IL-17下游基因相关的基因。我们发现，34/35（97%）的基因在转移性前列腺癌中的改变（改变率范围为3.42%至13.01%）显著多于原发性前列腺癌（改变率范围为0.40%至2.96%）。15/35（43%）的基因在原发性CRPC中的改变显著多于原发性HNPC。34/35（97%）的基因在转移性CRPC中的改变显著多于原发性HNPC。只有三个基因（IL17F、IL17RC和IL25）在转移性CRPC中的改变显著多于原发性CRPC。基因改变大多为基因扩增（97%），而基因深度缺失、错义突变和截短突变非常罕见。7/35（20%）的基因在原发性神经内分泌前列腺癌（NEPC）中的改变显著多于原发性腺癌（AC）。23/35（66%）的基因在转移性NEPC中的改变显著多于转移性AC。只有三个基因（IL17F、IL17RC和IL25）在具有神经内分泌特征的转移性NEPC中的改变显著多于转移性AC。转移性NEPC中的大多数基因改变为基因扩增（80%），而基因深度缺失、错义突变和截短突变非常罕见。我们的研究结果表明，IL-17及其相关基因的基因扩增在转移性CRPC和NEPC中比原发性激素未治疗的前列腺腺癌更常见，这意味着IL-17及其相关基因可能在从HNPC进展到CRPC、从原发部位转移以及转移性NEPC的发展中发挥重要作用。
