Tanaka Toshimichi, Kaida Takeshi, Yokoi Keigo, Ishii Satoru, Nishizawa Nobuyuki, Kawamata Hiroshi, Katoh Hiroshi, Sato Takeo, Nakamura Takatoshi, Watanabe Masahiko, Yamashita Keishi
Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
Division of Advanced Surgical Oncology, Department of Research and Development Centre for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
Oncol Lett. 2019 Jan;17(1):1257-1266. doi: 10.3892/ol.2018.9728. Epub 2018 Nov 19.
The PRL-3 gene is involved in the liver metastasis of colorectal cancer (CRC) and oncogene addiction to anticancer therapy. In the present study genomic gains in PRL-3 and its pathway genes, c-myc and EGFR, were investigated in order to determine their clinical relevance during metastatic formation in primary CRC and corresponding liver metastases. The genomic gain statuses of PRL-3, EGFR, and c-myc were investigated using quantitative polymerase chain reaction (qPCR) analysis in 35 samples of CRC and corresponding liver metastases. In the primary CRC specimens, genomic gains in PRL-3, c-myc, and EGFR were observed in 4, 4, and 13 cases, respectively. A genomic gain in one gene was observed in 18 cases, and these genomic gains were mutually exclusive. In the liver metastasis specimens, genomic gains were observed in 14, 8, and 13 cases, respectively. The copy numbers of PRL-3 and c-myc were significantly higher in the liver metastases than in the primary CRC specimens (P=0.03, P=0.009, respectively). A genomic gain in PRL-3 was the most frequent gain in the liver metastases (P=0.004) and was partially redundant with a c-myc genomic gain. EGFR genomic gains were consistent between the primary CRC and the liver metastases (P=0.0000008). In addition, a genomic gain in any of the 3 genes was observed in 23 cases (66%). Among the clinicopathological factors that were assessed, an EGFR genomic gain was significantly associated with tumour size in the primary CRC and the liver metastases (P=0.04). A c-myc genomic gain was also significantly associated with the v factor of the primary tumours in the liver metastases (P<0.01). In conclusion, the genomic copy numbers of PRL-3, c-myc and EGFR were frequently characterised by aberrations in genomic gain in liver metastases from CRC; thus, these gene statuses exhibit potential for the identification of patients who are likely to respond positively to anticancer therapies.
PRL-3基因与结直肠癌（CRC）的肝转移及抗癌治疗的癌基因成瘾有关。在本研究中，对PRL-3及其通路基因c-myc和EGFR的基因组扩增进行了研究，以确定它们在原发性CRC转移形成及相应肝转移过程中的临床相关性。采用定量聚合酶链反应（qPCR）分析，对35例CRC样本及相应肝转移样本中PRL-3、EGFR和c-myc的基因组扩增状态进行了研究。在原发性CRC标本中，分别在4例、4例和13例中观察到PRL-3、c-myc和EGFR的基因组扩增。在18例中观察到一个基因的基因组扩增，且这些基因组扩增相互排斥。在肝转移标本中，分别在14例、8例和13例中观察到基因组扩增。PRL-3和c-myc的拷贝数在肝转移中显著高于原发性CRC标本（分别为P=0.03，P=0.009）。PRL-3的基因组扩增是肝转移中最常见的扩增（P=0.004），且与c-myc基因组扩增部分重叠。原发性CRC和肝转移中EGFR基因组扩增情况一致（P=0.0000008）。此外，在23例（66%）中观察到这3个基因中任何一个的基因组扩增。在评估的临床病理因素中，EGFR基因组扩增与原发性CRC和肝转移中的肿瘤大小显著相关（P=0.04）。c-myc基因组扩增也与肝转移中原发性肿瘤的v因子显著相关（P<0.01）。总之，PRL-3、c-myc和EGFR的基因组拷贝数在CRC肝转移中常表现为基因组扩增异常；因此，这些基因状态显示出识别可能对抗癌治疗有积极反应患者的潜力。
