Prognostic Value of an Immune Long Non-Coding RNA Signature in Liver Hepatocellular Carcinoma
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
In recent years, there has been a growing recognition of the important role that long non-coding RNAs (lncRNAs) play in the immunological process of hepatocellular carcinoma (LIHC). An increasing number of studies have shown that certain lncRNAs hold great potential as viable options for diagnosis and treatment in clinical practice. The primary objective of our investigation was to devise an immune lncRNA profile to explore the significance of immune-associated lncRNAs in the accurate diagnosis and prognosis of LIHC. Gene expression profiles of LIHC samples obtained from TCGA database were screened for immune-related genes. The optimal immune-related lncRNA signature was built via correlational analysis, univariate and multivariate Cox analysis. Then, the Kaplan-Meier plot, ROC curve, clinical analysis, gene set enrichment analysis, and principal component analysis were performed to evaluate the capability of the immune lncRNA signature as a prognostic indicator. Six long non-coding RNAs were identified via correlation analysis and Cox regression analysis considering their interactions with immune genes. Subsequently, tumor samples were categorized into two distinct risk groups based on different clinical outcomes. Stratification analysis indicated that the prognostic ability of this signature acted as an independent factor. The KaplanMeier method was employed to conduct survival analysis, results showed a significant difference between the two risk groups. The predictive performance of this signature was validated by principal component analysis (PCA). Additionally, data obtained from gene set enrichment analysis (GSEA) revealed several potential biological processes in which these biomarkers may be involved. To summarize, this study demonstrated that this six-lncRNA signature could be identified as a potential factor that can independently predict the prognosis of LIHC patients.
Abstract
In recent years, there has been a growing recognition of the important role that long non-coding RNAs (lncRNAs) play in the immunological process of hepatocellular carcinoma (LIHC). An increasing number of studies have shown that certain lncRNAs hold great potential as viable options for diagnosis and treatment in clinical practice. The primary objective of our investigation was to devise an immune lncRNA profile to explore the significance of immune-associated lncRNAs in the accurate diagnosis and prognosis of LIHC. Gene expression profiles of LIHC samples obtained from TCGA database were screened for immune-related genes. The optimal immune-related lncRNA signature was built via correlational analysis, univariate and multivariate Cox analysis. Then, the Kaplan-Meier plot, ROC curve, clinical analysis, gene set enrichment analysis, and principal component analysis were performed to evaluate the capability of the immune lncRNA signature as a prognostic indicator. Six long non-coding RNAs were identified via correlation analysis and Cox regression analysis considering their interactions with immune genes. Subsequently, tumor samples were categorized into two distinct risk groups based on different clinical outcomes. Stratification analysis indicated that the prognostic ability of this signature acted as an independent factor. The KaplanMeier method was employed to conduct survival analysis, results showed a significant difference between the two risk groups. The predictive performance of this signature was validated by principal component analysis (PCA). Additionally, data obtained from gene set enrichment analysis (GSEA) revealed several potential biological processes in which these biomarkers may be involved. To summarize, this study demonstrated that this six-lncRNA signature could be identified as a potential factor that can independently predict the prognosis of LIHC patients.
참고문헌 (61)
- Sung H, "Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J. Clin, 71, pp.209~249 (2021)
- Takayama T, "Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma : a randomised trial", Lancet, 356, pp.802~807 (2000)
- Dimitroulis D, "From diagnosis to treatment of hepatocellular carcinoma : an epidemic problem for both developed and developing world", World J. Gastroenterol, 23, pp.5282~5294 (2017)
- Bruix J, "Management of hepatocellular carcinoma : an update", Hepatology, 53, pp.1020~1022 (2011)
- Forner A, "Hepatocellular carcinoma", Lancet, 391, pp.1301~1314 (2018)
- Sangro B, "Advances in immunotherapy for hepatocellular carcinoma", Nat. Rev. Gastroenterol. Hepatol, 18, pp.525~543 (2021)
- Kairaluoma V, "Toll-like receptor 5 and 8 in hepatocellular carcinoma", APMIS, 129, pp.470~479 (2021)
- Pinna F, "A20", TNFAIP3 discriminates tumor necrosis factor (TNF)-induced NF-kappaB from JNK pathway activation in hepatocytes, 2017, pp.8, 610~
- Pfister D, "NASH limits anti-tumour surveillance in immunotherapy-treated HCC", Nature, 592, pp.450~456 (2021)
- Ruf B, "Immunobiology and immunotherapy of HCC : spotlight on innate and innate-like immune cells", Cell Mol. Immunol, 18, pp.112~127 (2021)
- Rosenberg SA, "Adoptive cell transfer as personalized immunotherapy for human cancer", Science, 348, pp.62~68 (2015)
- Huang ZM, "Adjuvant cytokine-induced killer cells with minimally invasive therapies augmented therapeutic efficacy of unresectable hepatocellular carcinoma", J. Cancer Res. Ther, 16, pp.1603~1610 (2020)
- Ringelhan M, "The immunology of hepatocellular carcinoma", Nat. Immunol, 19, pp.222~232 (2018)
- Kim HJ, "Clinical significance of soluble programmed cell death ligand-1(sPD-L1)in hepatocellular carcinoma patients treated with radiotherapy", Radiother. Oncol, 129, pp.130~135 (2018)
- Long J, "Development and validation of a TP53-associated immune prognostic model for hepatocellular carcinoma", Ebiomedicine, 42, pp.363~374 (2019)
- Zhang J, "The long-noncoding RNA MALAT1 regulates TGF-beta", Smad signaling through formation of a lncRNA-protein complex with Smads, SETD2 and PPM1A in hepatic cells, 2020, pp.15, e228160~
- Djebali S, "Landscape of transcription in human cells", Nature, 489, pp.101~108 (2012)
- Derrien T, "The GENCODE v7 catalog of human long noncoding RNAs : analysis of their gene structure, evolution, and expression", Genome Res, 22, pp.1775~1789 (2012)
- Lv X, "FAL1 : a critical oncogenic long non-coding RNA in human cancers", Life Sci, 236, pp.116918~ (2019)
- Holoch D, "RNA-mediated epigenetic regulation of gene expression", Nat. Rev. Genet, 16, pp.71~84 (2015)
- Wang YL, "Lnc-UCID promotes G1", S transition and hepatoma growth by preventing DHX9-mediated CDK6 down-regulation, 2019, pp.70, 259~275
- Lin C, "Long non-coding RNA CRNDE promotes malignant progression of hepatocellular carcinoma through the miR-33a-5p", CDK6 axis, 2020, pp.76, 469~481
- Song P, "Genome-wide screening for differentially methylated long noncoding RNAs identifies LIFR-AS1 as an epigenetically regulated lncRNA that inhibits the progression of colorectal cancer", Clin. Epigenetics, 14, pp.138~ (2022)
- Wang C, "RNA sequencing analyses of gene expression during epstein-barr virus infection of primary B lymphocytes", J. Virol, 93, pp.e00226-19~ (2019)
- Unfried JP, "Long noncoding RNA IHCOLE promotes ligation efficiency of DNA double-strand breaks in hepatocellular carcinoma", Cancer Res, 81, pp.4910~4925 (2021)
- Peng WX, "LncRNA-mediated regulation of cell signaling in cancer", Oncogene, 36, pp.5661~5667 (2017)
- Su W, "LncRNA MIR22HG abrogation inhibits proliferation and induces apoptosis in esophageal adenocarcinoma cells via activation of the STAT3", c-Myc, Aging(Albany NY), pp.2019, 11[DOI]
- Wang BG, "The association of lncRNA-HULC polymorphisms with hepatocellular cancer risk and prognosis", Gene, 670, pp.148~154 (2018)
- Wang Y, "The long noncoding RNA HULC promotes liver cancer by increasing the expression of the HMGA2 oncogene via sequestration of the microRNA-186", J. Biol. Chem, 292, pp.15395~15407 (2017)
- Zhang J, "A transforming growth factor-beta and H19 signaling axis in tumor-initiating hepatocytes that regulates hepatic carcinogenesis", Hepatology, 69, pp.1549~1563 (2019)
- "The Cancer genome atlas"[URL]
- "Ensemble website"[URL]
- "Gene Set Enrichment Analysis"[URL]
- Shannon P, "Cytoscape : a software environment for integrated models of biomolecular interaction networks", Genome Res, 13, pp.2498~2504 (2003)
- Wang C, "Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types", Nat. Commun, 7, pp.10499~ (2016)
- Li S, "Exosomal long noncoding RNA lnc-GNAQ-6 : 1 may serve as a diagnostic marker for gastric cancer", Clin. Chim. Acta, 501, pp.252~257 (2019)
- Chao P, "lncRNA HOTAIR knockdown suppresses gastric cancer cell biological activities", Food Sci. Nutr, 9, pp.123~134 (2021)
- Vishnubalaji R, "Noncoding RNAs as potential mediators of resistance to cancer immunotherapy", Semin. Cancer Biol, 35, pp.65~79 (2019)
- DiStefano JK, "Long noncoding RNAs in the initiation, progression, and metastasis of hepatocellular carcinoma", Noncoding RNA Res, 2, pp.129~136 (2017)
- Ni W, "A novel lncRNA uc.134 represses hepatocellular carcinoma progression by inhibiting CUL4A-mediated ubiquitination of LATS1", J. Hematol. Oncol, 10, pp.91~ (2017)
- Zhang D, "Long non-coding RNA ANRIL indicates a poor prognosis of cervical cancer and promotes carcinogenesis via PI3K", Akt pathways, 2017, pp.85, 511~516
- Jiang R, "The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion", Nat. Commun, 8, pp.15129~ (2017)
- Liu X, "PD-1+ TIGIT+ CD8+ T cells are associated with pathogenesis and progression of patients with hepatitis B virus-related hepatocellular carcinoma", Cancer Immunol. Immunother, 68, pp.2041~2054 (2019)
- McLane LM, "CD8 T cell exhaustion during chronic viral infection and cancer", Annu. Rev. Immunol, 37, pp.457~495 (2019)
- Matos LL, "External validation of the AJCC Cancer Staging Manual, 8th edition, in an independent cohort of oral cancer patients", Oral Oncol, 71, pp.47~53 (2017)
- Zhou P, "Construction of an immune-related six-lncRNA signature to predict the outcomes, immune cell infiltration, and immunotherapy response in patients with hepatocellular carcinoma", Front. Oncol, 11, pp.661758~ (2021)
- Gao C, "Identification of senescence-associated long non-coding RNAs to predict prognosis and immune microenvironment in patients with hepatocellular carcinoma", Front. Genet, 13, pp.956094~ (2022)
- Zhou J, "Prediction of prognosis and chemotherapeutic sensitivity based on cuproptosisassociated lncRNAs in cervical squamous cell carcinoma and endocervical adenocarcinoma", Genes (Basel), 14, pp.1481~ (2023)
- Zhong F, "LncRNA AC099850.3 promotes hepatocellular carcinoma proliferation and invasion through PRR11", PI3K, J. Cancer, pp.2022, 13[DOI]
- Bird TG, "Alpha-fetoprotein detection of hepatocellular carcinoma leads to a standardized analysis of dynamic AFP to improve screening based detection", PLoS One, 11, pp.e156801~ (2016)
- Johnson P, "Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma", Nat. Rev. Gastroenterol. Hepatol, 19, pp.670~681 (2022)
- Tzartzeva K, "Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis", Gastroenterology, 154, pp.1706~1718 (2018)
- Galle PR, "Biology and significance of alpha-fetoprotein in hepatocellular carcinoma", Liver Int, 39, pp.2214~2229 (2019)
- Van Hees S, "Circulating predictive and diagnostic biomarkers for hepatitis B virus-associated hepatocellular carcinoma", World J. Gastroenterol, 22, pp.8271~8282 (2016)
- Sterling RK, "Frequency of elevated hepatocellular carcinoma(HCC)biomarkers in patients with advanced hepatitis C", Am. J. Gastroenrol, 107, pp.64~74 (2012)
- Bennett CL, "Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients", Aacta Neuropathol, 136, pp.425~443 (2018)
- Wymer KM, "Mildly elevated serum alpha-fetoprotein(AFP)among patients with testicular cancer may not be associated with residual cancer or need for treatment", Ann. Oncol, 28, pp.899~902 (2017)
- Sun W, "Regulatory mechanisms of long noncoding RNAs on gene expression in cancers", Cancer Genet, 216-217, pp.105~110 (2017)
- Huang D, "NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death", Nat. Immunol, 19, pp.1112~1125 (2018)
- Wu W, "LncRNA NKILA suppresses TGF-beta-induced epithelial-mesenchymal transition by blocking NF-κB signaling in breast cancer", Int. J. Cancer, 143, pp.2213~2224 (2018)
- Zhou Y, "LncRNA ID2-AS1 suppresses tumor metastasis by activating the HDAC8", ID2pathway in hepatocellular carcinoma, 2019, pp.469, 399~409
