scholarly journals A novel machine learning derived RNA-binding protein gene–based score system predicts prognosis of hepatocellular carcinoma patients

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12572
Author(s):  
Qiangnu Zhang ◽  
Yusen Zhang ◽  
Yusheng Guo ◽  
Honggui Tang ◽  
Mingyue Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Random Forest ◽  
Copy Number ◽  
Rna Binding ◽  
Expression Patterns ◽  
Rna Binding Protein ◽  
Cancer Genome ◽  
Random Forest Algorithm ◽  
Score System ◽  
Microarray Datasets

Background Although the expression of RNA-binding protein (RBP) genes in hepatocellular carcinoma (HCC) varies and is associated with tumor progression, there has been no overview study with multiple cohorts and large samples. The HCC-associated RBP genes need to be more accurately identified, and their clinical application value needs to be further explored. Methods First, we used the robust rank aggregation (RRA) algorithm to extract HCC-associated RBP genes from nine HCC microarray datasets and verified them in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and International Cancer Genome Consortium (ICGC) Japanese liver cancer (ICGC-LIRI-JP) cohort. In addition, the copy number variation (CNV), single-nucleotide variant (SNV), and promoter-region methylation data of HCC-associated RBP genes were analyzed. Using the random forest algorithm, we constructed an RBP gene–based prognostic score system (RBP-score). We then evaluated the ability of RBP-score to predict the prognosis of patients. The relationships between RBP-score and other clinical characteristics of patients were analyzed. Results The RRA algorithm identified 30 RBP mRNAs with consistent expression patterns across the nine HCC microarray datasets. These 30 RBP genes were defined as HCC-associated RBP genes. Their mRNA expression patterns were further verified in the TCGA-LIHC and ICGC-LIRI-JP cohorts. Among these 30 RBP genes, some showed significant copy number gain or loss, while others showed differences in the methylation levels of their promoter regions. Some RBP genes were risk factors or protective factors for the prognosis of patients. We extracted 10 key HCC-associated RBP genes using the random forest algorithm and constructed an RBP-score system. RBP-score effectively predicted the overall survival (OS) and disease-free survival (DFS) of HCC patients and was associated with the tumor, node, metastasis (TNM) stage, α-fetoprotein (AFP), and metastasis risk. The clinical value of RBP-score was validated in datasets from different platforms. Cox analysis suggested that a high RBP-score was an independent risk factor for poor prognosis in HCC patients. We also successfully established a combined RBP-score+TNM LASSO-Cox model that more accurately predicted the prognosis. Conclusion The RBP-score system constructed based on HCC-associated RBP genes is a simple and highly effective prognostic evaluation tool. It is suitable for different subgroups of HCC patients and has cross-platform characteristics. Combining RBP-score with the TNM staging system or other clinical parameters can lead to an even greater clinical benefit. In addition, the identified HCC-associated RBP genes may serve as novel targets for HCC treatment.

scholarly journals Cold-Inducible RNA Binding Protein as a Vaccination Platform to Enhance Immunotherapeutic Responses against Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3397
Author(s):  
Leyre Silva ◽  
Josune Egea ◽  
Lorea Villanueva ◽  
Marta Ruiz ◽  
Diana Llopiz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Rna Binding ◽  
Checkpoint Inhibitors ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
T Cell Responses ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Responses ◽  
Tlr4 Ligand

Therapies based on immune checkpoint inhibitors (ICPI) have yielded promising albeit limited results in patients with hepatocellular carcinoma (HCC). Vaccines have been proposed as combination partners to enhance response rates to ICPI. Thus, we analyzed the combined effect of a vaccine based on the TLR4 ligand cold-inducible RNA binding protein (CIRP) plus ICPI. Mice were immunized with vaccines containing ovalbumin linked to CIRP (OVA-CIRP), with or without ICPI, and antigen-specific responses and therapeutic efficacy were tested in subcutaneous and orthotopic mouse models of liver cancer. OVA-CIRP elicited polyepitopic T-cell responses, which were further enhanced when combined with ICPI (anti-PD-1 and anti-CTLA-4). Combination of OVA-CIRP with ICPI enhanced ICPI-induced therapeutic responses when tested in subcutaneous and intrahepatic B16-OVA tumors, as well as in the orthotopic PM299L HCC model. This effect was associated with higher OVA-specific T-cell responses in the periphery, although many tumor-infiltrating lymphocytes still displayed an exhausted phenotype. Finally, a new vaccine containing human glypican-3 linked to CIRP (GPC3-CIRP) induced clear responses in humanized HLA-A2.01 transgenic mice, which increased upon combination with ICPI. Therefore, CIRP-based vaccines may generate anti-tumor immunity to enhance ICPI efficacy in HCC, although blockade of additional checkpoint molecules and immunosuppressive targets should be also considered.

scholarly journals The RNA-binding protein RBM3 promotes cell proliferation in hepatocellular carcinoma by regulating circular RNA SCD-circRNA 2 production

EBioMedicine ◽  
2019 ◽  
Vol 45 ◽  
pp. 155-167 ◽  
Author(s):  
Wei Dong ◽  
Zhi-hui Dai ◽  
Fu-chen Liu ◽  
Xing-gang Guo ◽  
Chun-mei Ge ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Circular Rna

scholarly journals Overexpression of the RD RNA binding protein in hepatitis C virus-related hepatocellular carcinoma

2012 ◽  
Vol 28 (2) ◽  
pp. 728-734 ◽  
Author(s):  
MICHIHISA IIDA ◽  
NORIO IIZUKA ◽  
RYOUICHI TSUNEDOMI ◽  
MASAHIRO TSUTSUI ◽  
SHIN YOSHIDA ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals RNA Binding Protein HuR Promotes Autophagosome Formation by Regulating Expression of Autophagy-Related Proteins 5, 12, and 16 in Human Hepatocellular Carcinoma Cells

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Eunbyul Ji ◽  
Chongtae Kim ◽  
Hoin Kang ◽  
Sojin Ahn ◽  
Myeongwoo Jung ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Autophagic Flux ◽  
Autophagosome Formation ◽  
Cellular Autophagy ◽  
Related Proteins ◽  
Cellular Components ◽  
Hcc Cells

ABSTRACT Autophagy is a process of lysosomal self-degradation of cellular components by forming autophagosomes. Autophagosome formation is an essential process in autophagy and is fine-tuned by various autophagy-related gene (ATG) products, including ATG5, ATG12, and ATG16. Although several reports have shown that numerous factors affect multiple levels of gene regulation to orchestrate cellular autophagy, the detailed mechanism of autophagosome formation still needs further investigation. In this study, we demonstrate that the RNA binding protein HuR (human antigen R) performs an essential function in autophagosome formation. We observe that HuR silencing leads to inhibition of autophagosome formation and autophagic flux in liver cells. Ribonucleoprotein immunoprecipitation (RIP) assay allows the identification of ATG5, ATG12, and ATG16 mRNAs as the direct targets of HuR. We further show that HuR mediates the translation of ATG5, ATG12, and ATG16 mRNAs by binding to their 3′ untranslated regions (UTRs). In addition, we show that HuR expression positively correlates with the levels of ATG5 and ATG12 in hepatocellular carcinoma (HCC) cells. Collectively, our results suggest that HuR functions as a pivotal regulator of autophagosome formation by enhancing the translation of ATG5, ATG12, and ATG16 mRNAs and that augmented expression of HuR and ATGs may participate in the malfunction of autophagy in HCC cells.

Sign in / Sign up

Export Citation Format

Share Document