Fujishima Hajime, Fumoto Shoichi, Shibata Tomotaka, Nishiki Kohei, Tsukamoto Yoshiyuki, Etoh Tsuyoshi, Moriyama Masatsugu, Shiraishi Norio, Inomata Masafumi
Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan.
Department of Surgery, Oita Nakamura Hospital, Yufu, Oita, Japan.
PLoS One. 2017 Nov 14;12(11):e0188098. doi: 10.1371/journal.pone.0188098. eCollection 2017.
Recently, neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (NAC-DCF) was identified as a novel strong regimen with a high rate of pathological complete response (pCR) in advanced esophageal cancer in Japan. Predicting pCR will contribute to the therapeutic strategy and the prevention of surgical invasion. However, a predictor of pCR after NAC-DCF has not yet been developed. The aim of this study was to identify a novel predictor of pCR in locally advanced esophageal cancer treated with NAC-DCF.
A total of 32 patients who received NAC-DCF followed by esophagectomy between June 2013 and March 2016 were enrolled in this study. We divided the patients into the following 2 groups: pCR group (9 cases) and non-pCR group (23 cases), and compared gene expressions between these groups using DNA microarray data and KeyMolnet. Subsequently, a validation study of candidate molecular expression was performed in 7 additional cases.
Seventeen molecules, including transcription factor E2F, T-cell-specific transcription factor, Src (known as "proto-oncogene tyrosine-protein kinase of sarcoma"), interferon regulatory factor 1, thymidylate synthase, cyclin B, cyclin-dependent kinase (CDK) 4, CDK, caspase-1, vitamin D receptor, histone deacetylase, MAPK/ERK kinase, bcl-2-associated X protein, runt-related transcription factor 1, PR domain zinc finger protein 1, platelet-derived growth factor receptor, and interleukin 1, were identified as candidate molecules. The molecules were mainly associated with pathways, such as transcriptional regulation by SMAD, RB/E2F, and STAT. The validation study indicated that 12 of the 17 molecules (71%) matched the trends of molecular expression.
A 17-molecule set that predicts pCR after NAC-DCF for locally advanced esophageal cancer was identified.
最近，多西他赛/顺铂/5-氟尿嘧啶新辅助化疗（NAC-DCF）在日本被确定为晚期食管癌中具有高病理完全缓解（pCR）率的新型强效方案。预测pCR将有助于制定治疗策略并预防手术侵袭。然而，尚未开发出NAC-DCF后pCR的预测指标。本研究的目的是确定接受NAC-DCF治疗的局部晚期食管癌中pCR的新型预测指标。
本研究纳入了2013年6月至2016年3月期间接受NAC-DCF治疗后行食管切除术的32例患者。我们将患者分为以下两组：pCR组（9例）和非pCR组（23例），并使用DNA微阵列数据和KeyMolnet比较两组之间的基因表达。随后，在另外7例患者中进行了候选分子表达的验证研究。
确定了17种分子，包括转录因子E2F、T细胞特异性转录因子、Src（称为“肉瘤原癌基因酪氨酸蛋白激酶”）、干扰素调节因子1、胸苷酸合成酶、细胞周期蛋白B、细胞周期蛋白依赖性激酶（CDK）4、CDK、半胱天冬酶-1、维生素D受体、组蛋白脱乙酰酶、丝裂原活化蛋白激酶/细胞外信号调节激酶激酶、bcl-2相关X蛋白、 runt相关转录因子1、PR结构域锌指蛋白1、血小板衍生生长因子受体和白细胞介素1，作为候选分子。这些分子主要与SMAD、RB/E2F和STAT等转录调控途径相关。验证研究表明，17种分子中的12种（71%）与分子表达趋势相符。
确定了一组17种分子，可预测局部晚期食管癌NAC-DCF后的pCR。
