Basement Membrane-related Regulators for Prediction of Prognoses and Responses to Diverse Therapies in Hepatocellular Carcinoma

Overview

Journal BMC Med Genomics

Publisher Biomed Central

Specialty Genetics

Date 2023 Apr 20

PMID 37081465

Authors

Ruili Ding

Chuanbing Zhao

Yixin Jing

Rong Chen

Qingtao Meng

Affiliations

Soon will be listed here.

Abstract

Background: Hepatocellular carcinoma (HCC) remains a global health threat. Finding a novel biomarker for assessing the prognosis and new therapeutic targets is vital to treating this patient population. Our study aimed to explore the contribution of basement membrane-related regulators (BMR) to prognostic assessment and therapeutic response prediction in HCC.

Material And Methods: The RNA sequencing and clinical information of HCC were downloaded from TCGA-LIHC, ICGC-JP, GSE14520, GSE104580, and CCLE datasets. The BMR signature was created by the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and used to separate HCC patients into low- and high-risk groups. We conducted analyses using various R 4.1.3 software packages to compare prognoses and responses to immunotherapy, transcatheter arterial chemoembolization (TACE), and chemotherapeutic drugs between the groups. Additionally, stemness indices, molecular functions, and somatic mutation analyses were further explored in these subgroups.

Results: The BMR signature included 3 basement membrane-related genes (CTSA, P3H1, and ADAM9). We revealed that BMR signature was an independent risk contributor to poor prognosis in HCC, and high-risk group patients presented shorter overall survival. We discovered that patients in the high-risk group might be responsive to immunotherapy, while patients in the low-risk group may be susceptible to TACE therapy. Over 300 agents were screened to identify effective drugs for the two subgroups.

Conclusion: Overall, basement membrane-related regulators represent novel biomarkers in HCC for assessing prognosis, response to immunotherapy, the effectiveness of TACE therapy, and drug susceptibility.

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References

Leek J, Johnson W, Parker H, Jaffe A, Storey J . The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012; 28(6):882-3. PMC: 3307112. DOI: 10.1093/bioinformatics/bts034. View

Yamashita T, Koshikawa N, Shimakami T, Terashima T, Nakagawa M, Nio K . Serum Laminin γ2 Monomer as a Diagnostic and Predictive Biomarker for Hepatocellular Carcinoma. Hepatology. 2021; 74(2):760-775. DOI: 10.1002/hep.31758. View

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

Tong X, Ru Y, Fu J, Wang Y, Zhu J, Ding Y . Fucosylation Promotes Cytolytic Function and Accumulation of NK Cells in B Cell Lymphoma. Front Immunol. 2022; 13:904693. PMC: 9240281. DOI: 10.3389/fimmu.2022.904693. View

Wang L, Leite de Oliveira R, Huijberts S, Bosdriesz E, Pencheva N, Brunen D . An Acquired Vulnerability of Drug-Resistant Melanoma with Therapeutic Potential. Cell. 2018; 173(6):1413-1425.e14. DOI: 10.1016/j.cell.2018.04.012. View

Lin Z, Xu Q, Miao D, Yu F . An Inflammatory Response-Related Gene Signature Can Impact the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma. Front Oncol. 2021; 11:644416. PMC: 8019928. DOI: 10.3389/fonc.2021.644416. View

Geeleher P, Cox N, Huang R . Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines. Genome Biol. 2014; 15(3):R47. PMC: 4054092. DOI: 10.1186/gb-2014-15-3-r47. View

Ghandi M, Huang F, Jane-Valbuena J, Kryukov G, Lo C, McDonald 3rd E . Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature. 2019; 569(7757):503-508. PMC: 6697103. DOI: 10.1038/s41586-019-1186-3. View

Choi M, Sosman J, Zhang B . The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape. Cancers (Basel). 2021; 13(13). PMC: 8268428. DOI: 10.3390/cancers13133281. View

10.

Zhang R, Ma M, Lin X, Liu H, Chen J, Chen J . Extracellular matrix collagen I promotes the tumor progression of residual hepatocellular carcinoma after heat treatment. BMC Cancer. 2018; 18(1):901. PMC: 6145107. DOI: 10.1186/s12885-018-4820-9. View

11.

Friedman J, Hastie T, Tibshirani R . Regularization Paths for Generalized Linear Models via Coordinate Descent. J Stat Softw. 2010; 33(1):1-22. PMC: 2929880. View

12.

Peng Y, Liu C, Li M, Li W, Zhang M, Jiang X . Identification of a prognostic and therapeutic immune signature associated with hepatocellular carcinoma. Cancer Cell Int. 2021; 21(1):98. PMC: 7877064. DOI: 10.1186/s12935-021-01792-4. View

13.

Oh S, Park Y, Lee H, Lee J, Lee S, Baek Y . A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy. Cancers (Basel). 2020; 12(3). PMC: 7140088. DOI: 10.3390/cancers12030745. View

14.

Willumsen N, Jorgensen L, Karsdal M . Vastatin (the NC1 domain of human type VIII collagen a1 chain) is linked to stromal reactivity and elevated in serum from patients with colorectal cancer. Cancer Biol Ther. 2019; 20(5):692-699. PMC: 6606000. DOI: 10.1080/15384047.2018.1550571. View

15.

Meng C, He Y, Wei Z, Lu Y, Du F, Ou G . MRTF-A mediates the activation of COL1A1 expression stimulated by multiple signaling pathways in human breast cancer cells. Biomed Pharmacother. 2018; 104:718-728. DOI: 10.1016/j.biopha.2018.05.092. View

16.

Mayakonda A, Lin D, Assenov Y, Plass C, Koeffler H . Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res. 2018; 28(11):1747-1756. PMC: 6211645. DOI: 10.1101/gr.239244.118. View

17.

Yasuda H, Nakagawa M, Kiyokawa H, Yoshida E, Yoshimura T, Koshikawa N . Unique Biological Activity and Potential Role of Monomeric Laminin-γ2 as a Novel Biomarker for Hepatocellular Carcinoma: A Review. Int J Mol Sci. 2019; 20(1). PMC: 6337480. DOI: 10.3390/ijms20010226. View

18.

Wilkerson M, Hayes D . ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics. 2010; 26(12):1572-3. PMC: 2881355. DOI: 10.1093/bioinformatics/btq170. View

19.

Qin Y, Rodin S, Simonson O, Hollande F . Laminins and cancer stem cells: Partners in crime?. Semin Cancer Biol. 2016; 45:3-12. DOI: 10.1016/j.semcancer.2016.07.004. View

20.

Calderaro J, Couchy G, Imbeaud S, Amaddeo G, Letouze E, Blanc J . Histological subtypes of hepatocellular carcinoma are related to gene mutations and molecular tumour classification. J Hepatol. 2017; 67(4):727-738. DOI: 10.1016/j.jhep.2017.05.014. View