Fu Qiang, Yang Fan, Liao Minxue, Feeney Noel J, Deng Kevin, Serifis Nikolaos, Wei Liang, Yang Hongji, Chen Kai, Deng Shaoping, Markmann James F
Organ Transplantation Center, Sichuan Provincial People's Hospital and School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Front Oncol. 2019 Aug 7;9:737. doi: 10.3389/fonc.2019.00737. eCollection 2019.
Post-transplant (post-Tx) kidney cancer has become the second-highest cause of death in kidney recipients. Late diagnosis and treatment are the main reasons for high mortality. Further research into early diagnosis and potential treatment is therefore required. In this current study, through genome-wide RNA-Seq profile analysis of post-Tx malignant blood samples and post-Tx non-malignant control blood samples (CTRL-Tx), we found Rap GTPase Interactor (RADIL) and Aprataxin (APTX) to be the most meaningful markers for cancer diagnosis. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of the RADIL-APTX signature model was 0.92 ( < 0.0001). Similarly, the AUC of RADIL alone was 0.91 ( < 0.0001) and that of APTX was 0.81 ( = 0.001). Additionally, using a semi-supervised method, we found that RADIL alone could better predict malignancies in kidney transplantation recipients than APTX alone. Kaplan-Meier analysis indicated that RADIL was expressed significantly higher in the early stages (I and II) of kidney, liver, stomach, and pancreatic cancer, suggesting the potential use of RADIL in early diagnosis. Multivariable Cox regression analysis found that RADIL together with other factors (including age, stage III, stage IV and CD8+ T cells) play a key role in kidney cancer development. Among those factors, RADIL could promote kidney cancer development (HR > 1, < 0.05) while CD8+ T cells could inhibit kidney cancer development (HR < 1, < 0.05). RADIL may be a new immunotherapy target for kidney cancer post kidney transplantation.
移植后(post-Tx)肾癌已成为肾移植受者第二大死亡原因。诊断和治疗延迟是高死亡率的主要原因。因此,需要进一步研究早期诊断和潜在治疗方法。在本研究中,通过对移植后恶性血液样本和移植后非恶性对照血液样本(CTRL-Tx)进行全基因组RNA测序分析,我们发现Rap GTP酶相互作用分子(RADIL)和脱嘌呤嘧啶核酸内切酶(APTX)是癌症诊断最有意义的标志物。受试者工作特征(ROC)曲线分析表明,RADIL-APTX特征模型的曲线下面积(AUC)为0.92(<0.0001)。同样,单独RADIL的AUC为0.91(<0.0001),APTX的AUC为0.81(=0.001)。此外,使用半监督方法,我们发现单独的RADIL比单独的APTX能更好地预测肾移植受者的恶性肿瘤。Kaplan-Meier分析表明,RADIL在肾癌、肝癌、胃癌和胰腺癌的早期阶段(I期和II期)表达显著更高,提示RADIL在早期诊断中的潜在应用。多变量Cox回归分析发现,RADIL与其他因素(包括年龄、III期、IV期和CD8 + T细胞)共同在肾癌发展中起关键作用。在这些因素中,RADIL可促进肾癌发展(HR>1,<0.05),而CD8 + T细胞可抑制肾癌发展(HR<1,<0.05)。RADIL可能是肾移植后肾癌的一个新的免疫治疗靶点。