Genome‑wide investigation of the clinical implications and molecular mechanism of long noncoding RNA LINC00668 and protein‑coding genes in hepatocellular carcinoma

Wang,Xiangkun; Zhou,Xin; Liu,Junqi; Liu,Zhengqian; Zhang,Linbo; Gong,Yizhen; Huang,Jianlu; Yu,Long; Wang,Qiaoqi; Yang,Chengkun; Liao,Xiwen; Yu,Tingdong; Han,Chuangye; Zhu,Guangzhi; Ye,Xinping; Peng,Tao

doi:10.3892/ijo.2019.4858

Genome‑wide investigation of the clinical implications and molecular mechanism of long noncoding RNA LINC00668 and protein‑coding genes in hepatocellular carcinoma

Authors:
- Xiangkun Wang
- Xin Zhou
- Junqi Liu
- Zhengqian Liu
- Linbo Zhang
- Yizhen Gong
- Jianlu Huang
- Long Yu
- Qiaoqi Wang
- Chengkun Yang
- Xiwen Liao
- Tingdong Yu
- Chuangye Han
- Guangzhi Zhu
- Xinping Ye
- Tao Peng
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Affiliations: 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, Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China, Department of Hepatobiliary Surgery, Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530031, P.R. China, Department of Medical Cosmetology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530000, P.R. China
Published online on: August 14, 2019 https://doi.org/10.3892/ijo.2019.4858
Pages: 860-878
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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