Sains Malaysiana 51(1)(2022): 107-119

http://doi.org/10.17576/jsm-2022-5101-09

Identification of an Eight-LncRNA Signature as the Prognostic LncRNA Markers in Hepatocellular Carcinoma Patients

(Pengenalpastian Tandatangan Lapan-LncRNA sebagai Penanda LncRNA Prognostik dalam Pesakit Karsinoma Hepatosel)

DONGFANG WANG^1,2, TIANCHI LIU^1,2, WEIPING ZENG¹, SIXU LI³, KEAI SINN TAN^1,2,

WEN TAN² & LI GU*⁴

¹School of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, China

²Zhuhai Yuanzhi Health Technology Co. Ltd, Hengqin New Area, Zhuhai 519000, Guangdong, China

³Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology Guangzhou 510006, China

⁴Food and Health Engineering Research Center of State Education Ministry, Sun Yat-Sen University, Guangzhou 510275, China

Received: 12 January 2021/Accepted: 25 May 2021

ABSTRACT

Long non-coding RNA (lncRNA) signature has been reputable for the predetermination of cancer prognosis. In the present study, we constructed a lncRNA model to predict the survival outcomes for hepatocellular carcinoma (HCC) patients. Using the transcriptome data from TCGA HCC samples, we identified that NEAT1 and MALAT1 were highly expressed in HCC and other tumor subtypes compared to the adjacent normal tissues. Based on the LASSO Cox regression model, we identified an eight-lncRNA signature that significantly correlated with the overall survival and disease-free survival of the HCC training group. The prognostic value of this signature was validated using the test group. Further analysis suggested that this signature was associated with the clinicopathological parameters such as vascular tumor invasion, pathological stage, and tumor grade. Integrated functional analysis showed that these eight-lncRNAs were involved in the cell cycle, metabolic process, and immune response. In conclusion, we constructed an applicable eight-lncRNA signature that is robust and reliable for the prognosis of HCC. This signature may provide an efficient clinical prediction for HCC patients, and further study is required to uncover the function of the identified lncRNAs better.

Keywords: Cancer genome atlas; gene set enrichment analysis; hepatocellular carcinoma; long non-coding RNA; prognosis biomarkers

ABSTRAK

Tandatangan RNA bukan pengekodan panjang (lncRNA) telah terkenal untuk penentuan awal prognosis kanser. Dalam kajian ini, kami membina model lncRNA untuk meramalkan hasil kelangsungan hidup untuk pesakit karsinoma hepatosel (HCC). Menggunakan data transkrip daripada sampel TCGA HCC, kami mengenal pasti bahawa NEAT1 dan MALAT1 sangat dinyatakan dalam HCC dan sub-jenis tumor lain berbanding dengan tisu normal bersebelahan. Berdasarkan model regresi LASSO Cox, kami mengenal pasti tandatangan lapan-lncRNA yang berkorelasi dengan ketara kemandirian keseluruhan dan kelangsungan hidup bebas penyakit kumpulan latihan HCC. Nilai prognostik tandatangan ini telah disahkan menggunakan kumpulan ujian. Analisis lanjut mencadangkan bahawa tandatangan ini dikaitkan dengan parameter klinikopatologi seperti pencerobohan tumor vaskular, peringkat patologi dan gred tumor. Analisis fungsi bersepadu mendedahkan bahawa lapan-lncRNA ini terlibat dalam kitaran sel, proses metabolik dan tindak balas imun. Kesimpulannya, kami membina tandatangan lapan-lncRNA yang terpakai yang teguh dan boleh dipercayai untuk prognosis HCC. Tandatangan ini mungkin memberikan ramalan klinikal yang cekap untuk pesakit HCC dan kajian lanjut diperlukan untuk mendedahkan fungsi lncRNA yang dikenal pasti dengan lebih baik.

Kata kunci: Analisis pengayaan set gen; atlas genom kanser; biopenanda prognosis; karsinoma hepatosel; RNA bukan pengekodan panjang

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*Corresponding author; email: guli9@mail.sysu.edu.cn