Department of Obstetrics & Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.
Sci Rep. 2017 Oct 26;7(1):14160. doi: 10.1038/s41598-017-14418-5.
For endometrial cancer patients, lymphadenectomy is recommended to exclude rarely metastasized cancer cells. This procedure is performed even in patients with low risk of recurrence despite the risk of complications such as lymphedema. A method to accurately identify cases with no lymph node metastases (LN-) before lymphadenectomy is therefore highly required. We approached this clinical problem by examining primary lesions of endometrial cancers with CAGE (Cap Analysis Gene Expression), which quantifies promoter-level expression across the genome. Fourteen profiles delineated distinct transcriptional networks between LN + and LN- cases, within those classified as having the low or intermediate risk of recurrence. Subsequent quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses of 115 primary tumors showed SEMA3D mRNA and TACC2 isoforms expressed through a novel promoter as promising biomarkers with high accuracy (area under the receiver operating characteristic curve, 0.929) when used in combination. Our high-resolution transcriptome provided evidence of distinct molecular profiles underlying LN + /LN- status in endometrial cancers, raising the possibility of preoperative diagnosis to reduce unnecessary operations in patients with minimum recurrence risk.
对于子宫内膜癌患者，建议进行淋巴结切除术以排除罕见转移的癌细胞。尽管存在淋巴水肿等并发症的风险，但即使在复发风险低的患者中也会进行此手术。因此，非常需要一种在淋巴结切除术之前准确识别无淋巴结转移（LN-）病例的方法。我们通过使用 CAGE（Cap Analysis Gene Expression）检查子宫内膜癌的原发性病变来解决这个临床问题，该方法可定量测量整个基因组中启动子水平的表达。在那些被归类为复发风险低或中等的病例中，14 种特征描绘了 LN+和 LN-病例之间不同的转录网络。对 115 个原发性肿瘤的后续定量逆转录聚合酶链反应（qRT-PCR）分析表明，SEMA3D mRNA 和 TACC2 异构体通过一种新的启动子表达，是具有高准确性（接受者操作特征曲线下的面积，0.929）的有前途的生物标志物，当联合使用时。我们的高分辨率转录组为子宫内膜癌中 LN+/LN-状态的不同分子特征提供了证据，有可能在术前进行诊断，从而减少复发风险最小的患者的不必要手术。
