Zhang Yiyi, Guan Bingjie, Wu Yong, Du Fan, Zhuang Jinfu, Yang Yuanfeng, Guan Guoxian, Liu Xing
Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
J Inflamm Res. 2021 Nov 27;14:6275-6292. doi: 10.2147/JIR.S334096. eCollection 2021.
There are only limited studies on the long non-coding RNAs (lncRNAs) associated with neoadjuvant chemoradiotherapy (NCRT) response and prognosis of locally advanced rectal cancer (LARC) patients. This study identified lncRNAs associated with NCRT response and prognosis in CRC patients and explored their potential predictive mechanisms.
The study subjected the LncRNA expression profiles from our previous gene chip data to LASSO and identified a four-lncRNA signature that predicted NCRT response and prognosis. A Cox regression model was subsequently performed to identify the prognostic risk factors. The function of LINC00909, the lncRNA with the most powerful predictive ability, was finally identified in vivo and in vitro using CRC cell lines.
A comparison of the relative lncRNA expression of NCRT-responsive and non-responsive patients revealed four hub lncRNAs: DBET, LINC00909, FLJ33534, and HSD52 with AUC = 0.68, 0.73, 0.73, and 0.70, respectively (all p < 0.05). COX regression analysis further demonstrated that DBET, LINC00909 and FLJ33534 were associated with the DFS in CRC patients. The expression of the four lncRNAs was also significant in LARC patients who had not undergone NCRT (all p < 0.05). A risk score model was subsequently constructed based on the results of the multivariate COX analysis and used to predict NCRT response and prognosis in the CRC and LARC patients. The expression and prognosis of DBET, LINC00909 and FLJ33534 in the CRC tissues were further validated in the R2 platform and Oncomine database. Notably, overexpression of the LINC00909 increased the cell line resistance to the 5-FU and radiotherapy in vivo and in vitro.
DBET, LINC00909, and FLJ33534 are potential novel biomarkers for predicting NCRT response and prognosis in CRC patients. In particular, LINC00909 is an effective oncogene in CRC that could be used as a novel therapeutic target to enhance NCRT response.
关于与新辅助放化疗（NCRT）反应及局部晚期直肠癌（LARC）患者预后相关的长链非编码RNA（lncRNA）的研究有限。本研究鉴定了与结直肠癌（CRC）患者NCRT反应及预后相关的lncRNA，并探讨其潜在的预测机制。
本研究对我们之前基因芯片数据中的lncRNA表达谱进行套索分析（LASSO），鉴定出一个预测NCRT反应及预后的四lncRNA特征。随后进行Cox回归模型以确定预后风险因素。最后，使用CRC细胞系在体内和体外鉴定预测能力最强的lncRNA即LINC00909的功能。
对NCRT反应者和无反应者的相对lncRNA表达进行比较，发现四个关键lncRNA：DBET、LINC00909、FLJ33534和HSD52，其曲线下面积（AUC）分别为0.68、0.73、0.73和0.70（均p<0.05）。COX回归分析进一步表明，DBET、LINC00909和FLJ33534与CRC患者的无病生存期（DFS）相关。这四种lncRNA的表达在未接受NCRT的LARC患者中也具有显著性（均p<0.05）。随后基于多变量COX分析结果构建风险评分模型，用于预测CRC和LARC患者的NCRT反应及预后。DBET、LINC00909和FLJ33534在CRC组织中的表达及预后在R2平台和Oncomine数据库中得到进一步验证。值得注意的是，LINC00909的过表达在体内和体外均增加了细胞系对5-氟尿嘧啶（5-FU）和放疗的抗性。
DBET、LINC00909和FLJ33534是预测CRC患者NCRT反应及预后的潜在新型生物标志物。特别是，LINC00909是CRC中一种有效的癌基因，可作为增强NCRT反应的新型治疗靶点。
