Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Health Management and Division of Physical Examination, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Int J Oncol. 2019 Oct;55(4):860-878. doi: 10.3892/ijo.2019.4858. Epub 2019 Aug 14.
Hepatocellular carcinoma (HCC) is one of the leading causes of tumor‑related mortalities worldwide. Long noncoding RNAs have been reported to be associated with tumor initiation, progression and prognosis. The present study aimed to explore the association between long noncoding RNA LINC00668 and its co‑expression correlated protein‑coding genes (PCGs) in HCC. Data of 370 HCC patients from The Cancer Genome Atlas database were used for analysis. LINC00668 and its top 10 PCGs were selected to determine their diagnostic and prognostic value. Molecular mechanisms were explored to identify metabolic processes that LINC00668 and its PCGs are involved in. Prognosis‑related clinical factors and PCGs were used to construct a nomogram for predicting prognosis in HCC. A Connectivity Map was constructed to identify candidate target drugs for HCC. The top 10 PCGs identified were: Pyrimidineregic receptor P2Y4 (P2RY4), signal peptidase complex subunit 2 (SPCS2), family with sequence similarity 86 member C1 (FAM86C1), tudor domain containing 5 (TDRD5), ferritin light chain (FTL), stratifin (SFN), nucleolar complex associated 2 homolog (NOC2L), peroxiredoxin 1 (PRDX1), cancer/testis antigen 2 CTAG2 and leucine zipper and CTNNBIP1 domain containing (LZIC). FAM86C1, CTAG2 and SFN had significant diagnostic value for HCC (total area under the curve ≥0.7, P≤0.05); LINC00668, FAM86C1, TDRD5, FTL and SFN were of significant prognostic value for HCC (all P≤0.05). Investigation into the molecular mechanism indicated that LINC00668 affects cell division, cell cycle, mitotic nuclear division, and drug metabolism cytochrome P450 (all P≤0.05). The Connectivity Map identified seven candidate target drugs for the treatment of HCC, which were: Indolylheptylamine, mimosine, disopyramide, lidocaine, NU‑1025, bumetanide, and DQNLAOWBTJPFKL‑PKZXCIMASA‑N (all P≤0.05). Our findings indicated that LINC00668 may function as an oncogene and its overexpression indicates poor prognosis of HCC. FAM86C1, CTAG2 and SFN are of diagnostic significance, while FAM86C1, TDRD5, FTL and SFN are of prognostic significance for HCC.
肝细胞癌(HCC)是全球肿瘤相关死亡的主要原因之一。长链非编码 RNA 已被报道与肿瘤的发生、进展和预后有关。本研究旨在探讨长链非编码 RNA LINC00668 及其共表达相关蛋白编码基因(PCG)在 HCC 中的关联。使用来自癌症基因组图谱数据库的 370 例 HCC 患者的数据进行分析。选择 LINC00668 及其前 10 个 PCG 以确定其诊断和预后价值。通过探索代谢途径来研究分子机制,确定 LINC00668 及其 PCG 参与的代谢途径。使用与预后相关的临床因素和 PCG 构建 HCC 预后预测的列线图。构建 Connectivity Map 以识别 HCC 的候选靶向药物。鉴定出的前 10 个 PCG 为:嘧啶受体 P2Y4(P2RY4)、信号肽酶复合物亚基 2(SPCS2)、家族与序列相似性 86 成员 C1(FAM86C1)、结构域包含 5(TDRD5)、铁蛋白轻链(FTL)、层粘连蛋白(SFN)、核仁复合物相关 2 同源物(NOC2L)、过氧化物酶 1(PRDX1)、癌症/睾丸抗原 2 CTAG2 和亮氨酸拉链和 CTNNBIP1 结构域包含(LZIC)。FAM86C1、CTAG2 和 SFN 对 HCC 具有显著的诊断价值(总曲线下面积≥0.7,P≤0.05);LINC00668、FAM86C1、TDRD5、FTL 和 SFN 对 HCC 具有显著的预后价值(均 P≤0.05)。分子机制研究表明,LINC00668 影响细胞分裂、细胞周期、有丝分裂核分裂和药物代谢细胞色素 P450(均 P≤0.05)。Connectivity Map 鉴定出七种治疗 HCC 的候选靶向药物,分别为:吲哚基庚基胺、含羞草氨酸、二异丙吡胺、利多卡因、NU-1025、布美他尼和 DQNLAOWBTJPFKL-PKZXCIMASA-N(均 P≤0.05)。我们的研究结果表明,LINC00668 可能作为一种癌基因发挥作用,其过表达提示 HCC 预后不良。FAM86C1、CTAG2 和 SFN 具有诊断意义,而 FAM86C1、TDRD5、FTL 和 SFN 对 HCC 具有预后意义。