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Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Hepatocellular Carcinoma | Research

Construction and verification of a novel circadian clock related long non-coding RNA model and prediction of treatment for survival prognosis in patients with hepatocellular carcinoma

Authors: Zhen Zhang, Wenhui Gao, Xiaoning Tan, Tianhao Deng, Wanshuang Zhou, Huiying Jian, Puhua Zeng

Published in: BMC Cancer | Issue 1/2023

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Abstract

Circadian clock genes are significant in the occurrence and development of HCC and long-non coding RNAs (lncRNAs) are closely related to HCC progression. In this study, we aimed to establish a prognostic risk model for HCC. Circadian clock-related lncRNAs expressed in HCC were extracted from The Cancer Genome Atlas. A nomogram was established to predict individual survival rate. Biological processes enriched for risk model transcripts were investigated by Gene Set Enrichment Analysis. Further, we evaluated the relationship between risk score and immune-checkpoint inhibitor-related gene expression level. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to assess the sensitivity of tumors in high- and low-risk score groups to different drugs. A total of 11 circadian clock-related lncRNAs were included in multi-Cox proportional hazards model analysis to establish a risk model. Univariate and multivariate Cox regression analysis showed that the risk model was an independent risk factor in HCC. The risk model was a significantly associated with the immune signature. Further GDSC analysis indicated that patients in each risk score group may be sensitive to different anti-cancer drugs. QRT-PCR analysis results showed that C012073.1, PRRT3-AS1, TMCC1-AS1, LINC01138, MKLN1-AS, KDM4A-AS1, AL031985.3, POLH-AS1, LINC01224, and AC099850.3 were more highly expressed in Huh-7 and HepG2, compared to LO2, while AC008549.1 were lower expressed. Our work established a prognostic model for HCC. Risk score analysis indicated that the model is significantly associated with modulation tumor immunity and could be used to guide more effective therapeutic strategies in the future.
Literature
1.
go back to reference Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRef Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRef
2.
go back to reference Anwanwan D, Singh SK, Singh S, Saikam V, Singh R. Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta Rev Cancer. 2020;1873:188314.CrossRef Anwanwan D, Singh SK, Singh S, Saikam V, Singh R. Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta Rev Cancer. 2020;1873:188314.CrossRef
3.
go back to reference Vibert E, Schwartz M, Olthoff KM. Advances in resection and transplantation for hepatocellular carcinoma. J Hepatol. 2020;72:262–76.CrossRef Vibert E, Schwartz M, Olthoff KM. Advances in resection and transplantation for hepatocellular carcinoma. J Hepatol. 2020;72:262–76.CrossRef
4.
go back to reference Hilmi M, Neuzillet C, Calderaro J, Lafdil F, Pawlotsky JM, Rousseau B. Angiogenesis and immune checkpoint inhibitors as therapies for hepatocellular carcinoma: current knowledge and future research directions. J Immunother Cancer. 2019;7:333.CrossRef Hilmi M, Neuzillet C, Calderaro J, Lafdil F, Pawlotsky JM, Rousseau B. Angiogenesis and immune checkpoint inhibitors as therapies for hepatocellular carcinoma: current knowledge and future research directions. J Immunother Cancer. 2019;7:333.CrossRef
5.
go back to reference Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial. J Clin Oncol. 2020;38:193–202.CrossRef Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial. J Clin Oncol. 2020;38:193–202.CrossRef
6.
go back to reference Liu Z, Lin Y, Zhang J, Zhang Y, Li Y, Liu Z, et al. Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma. J Exp Clin Cancer Res. 2019;38:447.CrossRef Liu Z, Lin Y, Zhang J, Zhang Y, Li Y, Liu Z, et al. Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma. J Exp Clin Cancer Res. 2019;38:447.CrossRef
7.
go back to reference Arita J, Ichida A, Nagata R, Mihara Y, Kawaguchi Y, Ishizawa T, et al. Conversion surgery after preoperative therapy for advanced hepatocellular carcinoma in the era of molecular targeted therapy and immune checkpoint inhibitors. J Hepatobiliary Pancreat Sci. 2022;29:732.CrossRef Arita J, Ichida A, Nagata R, Mihara Y, Kawaguchi Y, Ishizawa T, et al. Conversion surgery after preoperative therapy for advanced hepatocellular carcinoma in the era of molecular targeted therapy and immune checkpoint inhibitors. J Hepatobiliary Pancreat Sci. 2022;29:732.CrossRef
8.
go back to reference Kim N, You MW. Hepatocellular carcinoma and macrovascular tumor thrombosis: treatment outcomes and prognostic factors for survival. Jpn J Radiol. 2019;37:781–92.CrossRef Kim N, You MW. Hepatocellular carcinoma and macrovascular tumor thrombosis: treatment outcomes and prognostic factors for survival. Jpn J Radiol. 2019;37:781–92.CrossRef
9.
go back to reference Zhang Z, Zeng P, Gao W, Zhou Q, Feng T, Tian X. Circadian clock: a regulator of the immunity in cancer. Cell Commun Signal. 2021;19:37.CrossRef Zhang Z, Zeng P, Gao W, Zhou Q, Feng T, Tian X. Circadian clock: a regulator of the immunity in cancer. Cell Commun Signal. 2021;19:37.CrossRef
10.
go back to reference Zhou L, Zhang Z, Nice E, Huang C, Zhang W, Tang Y. Circadian rhythms and cancers: the intrinsic links and therapeutic potentials. J Hematol Oncol. 2022;15:21.CrossRef Zhou L, Zhang Z, Nice E, Huang C, Zhang W, Tang Y. Circadian rhythms and cancers: the intrinsic links and therapeutic potentials. J Hematol Oncol. 2022;15:21.CrossRef
11.
go back to reference Crespo M, Leiva M, Sabio G. Circadian clock and liver cancer. Cancers (Basel). 2021;13:3631.CrossRef Crespo M, Leiva M, Sabio G. Circadian clock and liver cancer. Cancers (Basel). 2021;13:3631.CrossRef
12.
go back to reference Fu L, Pelicano H, Liu J, Huang P, Lee C. The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell. 2002;111:41–50.CrossRef Fu L, Pelicano H, Liu J, Huang P, Lee C. The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell. 2002;111:41–50.CrossRef
13.
go back to reference Filipski E, Lévi F. Circadian disruption in experimental cancer processes. Integr Cancer Ther. 2009;8:298–302.CrossRef Filipski E, Lévi F. Circadian disruption in experimental cancer processes. Integr Cancer Ther. 2009;8:298–302.CrossRef
14.
go back to reference Lin YM, Chang JH, Yeh KT, Yang MY, Liu TC, Lin SF, et al. Disturbance of circadian gene expression in hepatocellular carcinoma. Mol Carcinog. 2008;47:925–33.CrossRef Lin YM, Chang JH, Yeh KT, Yang MY, Liu TC, Lin SF, et al. Disturbance of circadian gene expression in hepatocellular carcinoma. Mol Carcinog. 2008;47:925–33.CrossRef
15.
go back to reference Chandra Gupta S, Nandan Tripathi Y. Potential of long non-coding RNAs in cancer patients: from biomarkers to therapeutic targets. Int J Cancer. 2017;140:1955–67.CrossRef Chandra Gupta S, Nandan Tripathi Y. Potential of long non-coding RNAs in cancer patients: from biomarkers to therapeutic targets. Int J Cancer. 2017;140:1955–67.CrossRef
16.
go back to reference Mosig RA, Kojima S. Timing without coding: How do long non-coding RNAs regulate circadian rhythms. Semin Cell Dev Biol. 2022;126:79.CrossRef Mosig RA, Kojima S. Timing without coding: How do long non-coding RNAs regulate circadian rhythms. Semin Cell Dev Biol. 2022;126:79.CrossRef
17.
go back to reference Yang Z, Li X, Yang Y, He Z, Qu X, Zhang Y. Long noncoding RNAs in the progression, metastasis, and prognosis of osteosarcoma. Cell Death Dis. 2016;7:e2389.CrossRef Yang Z, Li X, Yang Y, He Z, Qu X, Zhang Y. Long noncoding RNAs in the progression, metastasis, and prognosis of osteosarcoma. Cell Death Dis. 2016;7:e2389.CrossRef
18.
go back to reference Li P, Zhang K, Tang S, Tang W. Knockdown of lncRNA HAGLROS inhibits metastasis and promotes apoptosis in nephroblastoma cells by inhibition of autophagy. Bioengineered. 2022;13:7552–62.CrossRef Li P, Zhang K, Tang S, Tang W. Knockdown of lncRNA HAGLROS inhibits metastasis and promotes apoptosis in nephroblastoma cells by inhibition of autophagy. Bioengineered. 2022;13:7552–62.CrossRef
19.
go back to reference Yeermaike A, Gu P, Liu D, Nadire T. LncRNA NEAT1 sponges miR-214 to promoted tumor growth in hepatocellular carcinoma. Mamm Genome. 2022;33:525.CrossRef Yeermaike A, Gu P, Liu D, Nadire T. LncRNA NEAT1 sponges miR-214 to promoted tumor growth in hepatocellular carcinoma. Mamm Genome. 2022;33:525.CrossRef
20.
go back to reference Cui M, Zheng M, Sun B, Wang Y, Ye L, Zhang X. A long noncoding RNA perturbs the circadian rhythm of hepatoma cells to facilitate hepatocarcinogenesis. Neoplasia. 2015;17:79–88.CrossRef Cui M, Zheng M, Sun B, Wang Y, Ye L, Zhang X. A long noncoding RNA perturbs the circadian rhythm of hepatoma cells to facilitate hepatocarcinogenesis. Neoplasia. 2015;17:79–88.CrossRef
21.
go back to reference Wang S, Lin Y, Li F, Qin Z, Zhou Z, Gao L, et al. An NF-κB-driven lncRNA orchestrates colitis and circadian clock. Sci Adv. 2020;6:eabb5202.CrossRef Wang S, Lin Y, Li F, Qin Z, Zhou Z, Gao L, et al. An NF-κB-driven lncRNA orchestrates colitis and circadian clock. Sci Adv. 2020;6:eabb5202.CrossRef
22.
go back to reference Ye Y, Xiang Y, Ozguc FM, Kim Y, Liu CJ, Park PK, et al. The genomic landscape and pharmacogenomic interactions of clock genes in cancer chronotherapy. Cell Syst. 2018;6:314-28.e2.CrossRef Ye Y, Xiang Y, Ozguc FM, Kim Y, Liu CJ, Park PK, et al. The genomic landscape and pharmacogenomic interactions of clock genes in cancer chronotherapy. Cell Syst. 2018;6:314-28.e2.CrossRef
23.
go back to reference Chakrabarti S, Michor F. Circadian clock effects on cellular proliferation: insights from theory and experiments. Curr Opin Cell Biol. 2020;67:17–26.CrossRef Chakrabarti S, Michor F. Circadian clock effects on cellular proliferation: insights from theory and experiments. Curr Opin Cell Biol. 2020;67:17–26.CrossRef
24.
go back to reference Rana S, Mahmood S. Circadian rhythm and its role in malignancy. J Circadian Rhythms. 2010;8:3.CrossRef Rana S, Mahmood S. Circadian rhythm and its role in malignancy. J Circadian Rhythms. 2010;8:3.CrossRef
25.
go back to reference Sahar S, Sassone-Corsi P. Metabolism and cancer: the circadian clock connection. Nat Rev Cancer. 2009;9:886–96.CrossRef Sahar S, Sassone-Corsi P. Metabolism and cancer: the circadian clock connection. Nat Rev Cancer. 2009;9:886–96.CrossRef
26.
go back to reference Liu S, Peng X, Wu X, Bu F, Yu Z, Zhu J, et al. Construction of a new immune-related lncRNA model and prediction of treatment and survival prognosis of human colon cancer. World J Surg Oncol. 2022;20:71.CrossRef Liu S, Peng X, Wu X, Bu F, Yu Z, Zhu J, et al. Construction of a new immune-related lncRNA model and prediction of treatment and survival prognosis of human colon cancer. World J Surg Oncol. 2022;20:71.CrossRef
27.
go back to reference Yang W, Soares J, Greninger P, Edelman EJ, Lightfoot H, Forbes S, et al. Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 2013;41:D955–61.CrossRef Yang W, Soares J, Greninger P, Edelman EJ, Lightfoot H, Forbes S, et al. Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 2013;41:D955–61.CrossRef
28.
go back to reference Geeleher P, Cox NJ, Huang RS. Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines. Genome Biol. 2014;15:R47.CrossRef Geeleher P, Cox NJ, Huang RS. Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines. Genome Biol. 2014;15:R47.CrossRef
29.
go back to reference Zhou M, Wu T, Yuan Y, Dong SJ, Zhang ZM, Wang Y, Wang J. A risk score system based on a six-microRNA signature predicts the overall survival of patients with ovarian cancer. J Ovarian Res. 2022;15(1):54. Zhou M, Wu T, Yuan Y, Dong SJ, Zhang ZM, Wang Y, Wang J. A risk score system based on a six-microRNA signature predicts the overall survival of patients with ovarian cancer. J Ovarian Res. 2022;15(1):54.
30.
go back to reference Wang Y, Zhao X, Li J, Wang X, Hu W, Zhang X. Four m6A RNA methylation gene signatures and their prognostic values in lung adenocarcinoma. Technol Cancer Res Treat. 2022;21:15330338221085372.CrossRef Wang Y, Zhao X, Li J, Wang X, Hu W, Zhang X. Four m6A RNA methylation gene signatures and their prognostic values in lung adenocarcinoma. Technol Cancer Res Treat. 2022;21:15330338221085372.CrossRef
31.
go back to reference Zhang H, Shu R, Liu X, Zhang X, Sun D. Downregulation of REV-ERBα is associated with the progression of lung adenocarcinoma. Ann Transl Med. 2022;10:56.CrossRef Zhang H, Shu R, Liu X, Zhang X, Sun D. Downregulation of REV-ERBα is associated with the progression of lung adenocarcinoma. Ann Transl Med. 2022;10:56.CrossRef
32.
go back to reference Kudo M. Scientific rationale for combination immunotherapy of hepatocellular carcinoma with anti-PD-1/PD-L1 and Anti-CTLA-4 antibodies. Liver Cancer. 2019;8:413–26.CrossRef Kudo M. Scientific rationale for combination immunotherapy of hepatocellular carcinoma with anti-PD-1/PD-L1 and Anti-CTLA-4 antibodies. Liver Cancer. 2019;8:413–26.CrossRef
33.
go back to reference Zhu Q, Wu X, Ma L, et al. Apoptosis-Associated Gene expression profiling is one new prognosis risk predictor of human rectal Cancer. Dis Markers. 2022;2022:4596810.CrossRef Zhu Q, Wu X, Ma L, et al. Apoptosis-Associated Gene expression profiling is one new prognosis risk predictor of human rectal Cancer. Dis Markers. 2022;2022:4596810.CrossRef
34.
go back to reference Fan L, Li H, Wang W. Long non-coding RNA PRRT3-AS1 silencing inhibits prostate cancer cell proliferation and promotes apoptosis and autophagy. Exp Physiol. 2020;105(5):793–808.CrossRef Fan L, Li H, Wang W. Long non-coding RNA PRRT3-AS1 silencing inhibits prostate cancer cell proliferation and promotes apoptosis and autophagy. Exp Physiol. 2020;105(5):793–808.CrossRef
35.
go back to reference Chen C, Su N, Li G, Shen Y, Duan X. Long non-coding RNA TMCC1-AS1 predicts poor prognosis and accelerates epithelial-mesenchymal transition in liver cancer. Oncol Lett. 2021;22(5):773.CrossRef Chen C, Su N, Li G, Shen Y, Duan X. Long non-coding RNA TMCC1-AS1 predicts poor prognosis and accelerates epithelial-mesenchymal transition in liver cancer. Oncol Lett. 2021;22(5):773.CrossRef
36.
go back to reference Chen T, Liu R, Niu Y, et al. HIF-1α-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p/KPNA2/AKT pathway. Cell Death Dis. 2021;12(12):1152.CrossRef Chen T, Liu R, Niu Y, et al. HIF-1α-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p/KPNA2/AKT pathway. Cell Death Dis. 2021;12(12):1152.CrossRef
37.
go back to reference Zhong F, Liu S, Hu D, Chen L. LncRNA AC099850.3 promotes hepatocellular carcinoma proliferation and invasion through PRR11/PI3K/AKT axis and is associated with patients prognosis. J Cancer. 2022;13(3):1048–60.CrossRef Zhong F, Liu S, Hu D, Chen L. LncRNA AC099850.3 promotes hepatocellular carcinoma proliferation and invasion through PRR11/PI3K/AKT axis and is associated with patients prognosis. J Cancer. 2022;13(3):1048–60.CrossRef
38.
go back to reference Guo C, Zhou S, Yi W, et al. SOX9/MKLN1-AS axis induces hepatocellular carcinoma proliferation and epithelial-mesenchymal transition. Biochem Genet. 1914;2022:60. Guo C, Zhou S, Yi W, et al. SOX9/MKLN1-AS axis induces hepatocellular carcinoma proliferation and epithelial-mesenchymal transition. Biochem Genet. 1914;2022:60.
39.
go back to reference Gong A, Luo X, Tan Y, Chen H, Luo G. High expression of C10orf91 and LINC01224 in hepatocellular carcinoma and poor prognosis. Am J Transl Res. 2022;14(4):2567–79. Gong A, Luo X, Tan Y, Chen H, Luo G. High expression of C10orf91 and LINC01224 in hepatocellular carcinoma and poor prognosis. Am J Transl Res. 2022;14(4):2567–79.
40.
go back to reference Song Z, Cheng L, Lu L, Lu W, Zhou Y, Wang Z. Development and validation of the nomograms for predicting overall survival and cancer-specific survival in patients with synovial sarcoma. Front Endocrinol (Lausanne). 2021;12:764571.CrossRef Song Z, Cheng L, Lu L, Lu W, Zhou Y, Wang Z. Development and validation of the nomograms for predicting overall survival and cancer-specific survival in patients with synovial sarcoma. Front Endocrinol (Lausanne). 2021;12:764571.CrossRef
Metadata
Title
Construction and verification of a novel circadian clock related long non-coding RNA model and prediction of treatment for survival prognosis in patients with hepatocellular carcinoma
Authors
Zhen Zhang
Wenhui Gao
Xiaoning Tan
Tianhao Deng
Wanshuang Zhou
Huiying Jian
Puhua Zeng
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10508-y

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