The DOI matches its Crossref record; 69 of the 71 references it cites were found in a registry or an index.
Deep learning-based multi-omics integration robustly predicts survival in liver cancer
Open accessPublished version of a preprint
Abstract
Identifying robust survival subgroups of hepatocellular carcinoma (HCC) will significantly improve patient care. Currently, endeavor of integrating multi-omics data to explicitly predict HCC survival from multiple patient cohorts is lacking. To fill this gap, we present a deep learning (DL)–based model on HCC that robustly differentiates survival subpopulations of patients in six cohorts. We built the DL-based, survival-sensitive model on 360 HCC patients' data using RNA sequencing (RNA-Seq), miRNA sequencing (miRNA-Seq), and methylation data from The Cancer Genome Atlas (TCGA), which predicts prognosis as good as an alternative model where genomics and clinical data are both considered. This DL-based model provides two optimal subgroups of patients with significant survival differences (P = 7.13e−6) and good model fitness [concordance index (C-index) = 0.68]. More aggressive subtype is associated with frequent TP53 inactivation mutations, higher expression of stemness markers (KRT19 and EPCAM) and tumor marker BIRC5, and activated Wnt and Akt signaling pathways. We validated this multi-omics model on five external datasets of various omics types: LIRI-JP cohort (n = 230, C-index = 0.75), NCI cohort (n = 221, C-index = 0.67), Chinese cohort (n = 166, C-index = 0.69), E-TABM-36 cohort (n = 40, C-index = 0.77), and Hawaiian cohort (n = 27, C-index = 0.82). This is the first study to employ DL to identify multi-omics features linked to the differential survival of patients with HCC. Given its robustness over multiple cohorts, we expect this workflow to be useful at predicting HCC prognosis prediction. Clin Cancer Res; 24(6); 1248–59. ©2017 AACR.
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“Particularly in cancer patient survival subtyping with multi-omics modalities, this sequence of steps has become popular [25–31, 34].”
From Multimodal deep learning for biomedical data fusion: a review (2022) · cites this paper as [25]
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“In liver cancer research, Chaudhary et al. employed multi-omics data integration to predict the prognosis of hepatocellular carcinoma (HCC) and identify subgroups with significant survival differences [112].”
From Challenges in AI-driven Biomedical Multimodal Data Fusion and Analysis (2025) · cites this paper as [112]
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Scikit-learn: Machine Learning in Python
Pedregosa, F., Varoquaux, G., Gramfort, A., Michel, V., Thirion, B., Grisel, O., Blondel, M., Müller, A., Nothman, J., Louppe, G., et al. (2012) · arXiv · doi:10.48550/arxiv.1201.0490 · Cited by 71,016
limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Global cancer statistics, 2012
Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet‐Tieulent, J., & Jemal, A. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21262 · Cited by 27,235
Regression Models and Life-Tables
Cox, D. R. (1992) · Springer Series in Statistics · doi:10.1007/978-1-4612-4380-9_37 · Cited by 26,297
Silhouettes: A graphical aid to the interpretation and validation of cluster analysis
Rousseeuw, P. J. (1987) · Journal of Computational and Applied Mathematics · doi:10.1016/0377-0427(87)90125-7 · Cited by 21,392
Regularization and Variable Selection Via the Elastic Net
Zou, H., & Hastie, T. (2005) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.1467-9868.2005.00503.x · Cited by 20,957
Regularization Paths for Generalized Linear Models via Coordinate Descent
Friedman, J., Hastie, T., & Tibshirani, R. (2010) · Journal of Statistical Software · doi:10.18637/jss.v033.i01 · Cited by 19,927
Siegel, R. L., Miller, K. D., & Jemal, A. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21332 · Cited by 16,003
Research works printed but not linked: 1
- Steck, 2007 3–6, On ranking in survival analysis: bounds on the concordance index
Cited by
Sorted by citations
Items 101–121 of 121
Patel, S. K., George, B., & Rai, V. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01177 · Cited by 102
Ghosh, S., Zhao, X., Alim, M., Brudno, M., & Bhat, M. (2024) · Gut · doi:10.1136/gutjnl-2023-331740 · Cited by 110
Deep learning-based ovarian cancer subtypes identification using multi-omics data
Guo, L.-Y., Wu, A.-H., Wang, Y.-X., Zhang, L.-P., Chai, H., & Liang, X.-F. (2020) · BioData Mining · doi:10.1186/s13040-020-00222-x · Cited by 89
Zhang, X., Zhang, J., Sun, K., Yang, X., Dai, C., & Guo, Y. (2019) · 2019 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) · doi:10.1109/bibm47256.2019.8983228 · Cited by 93
Predicting and characterizing a cancer dependency map of tumors with deep learning
Chiu, Y.-C., Zheng, S., Wang, L.-J., Iskra, B. S., Rao, M. K., Houghton, P. J., Huang, Y., & Chen, Y. (2021) · Science Advances · doi:10.1126/sciadv.abh1275 · Cited by 84
“DL is increasingly being used in genomics research for cancer survival ( 11 , 12 ) and cancer classification ( 13 – 15 ).”
MethodMachine-aided self-diagnostic prediction models for polycystic ovary syndrome: observational study
Zigarelli, A., Jia, Z., & Lee, H. (2022) · JMIR Formative Research · doi:10.2196/29967 · Cited by 74
“Objectives Machine learning and deep learning techniques have been widely used to analyze health data and improve diagnostic accuracy and precision, disease treatment, and prevention [16,17].”
MethodImproved survival analysis by learning shared genomic information from pan-cancer data
Kim, S., Kim, K., Choe, J., Lee, I., & Kang, J. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa462 · Cited by 77
Challenges in AI-driven Biomedical Multimodal Data Fusion and Analysis
Liu, J., Cen, X., Yi, C., Wang, F.-A., Ding, J., Cheng, J., Wu, Q., Gai, B., Zhou, Y., He, R., et al. (2025) · Genomics, Proteomics & Bioinformatics · doi:10.1093/gpbjnl/qzaf011 · Cited by 75
Seal, D. B., Das, V., Goswami, S., & De, R. K. (2020) · Genomics · doi:10.1016/j.ygeno.2020.03.021 · Cited by 69
Albaradei, S., Napolitano, F., Thafar, M. A., Gojobori, T., Essack, M., & Gao, X. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.08.006 · Cited by 61
Divate, M., Tyagi, A., Richard, D. J., Prasad, P. A., Gowda, H., & Nagaraj, S. H. (2022) · Cancers · doi:10.3390/cancers14051185 · Cited by 55
Ning, Z., Pan, W., Chen, Y., Xiao, Q., Zhang, X., Luo, J., Wang, J., & Zhang, Y. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa056 · Cited by 53
Artificial Intelligence and Organ Transplantation: Challenges and Expectations
Briceño, J. (2020) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0000000000000775 · Cited by 46
Lv, J., Wang, J., Shang, X., Liu, F., & Guo, S. (2020) · Bioscience Reports · doi:10.1042/bsr20201482 · Cited by 33
Goel, I., Bhaskar, Y., Kumar, N., Singh, S., Amanullah, M., Dhar, R., & Karmakar, S. (2025) · Frontiers in Digital Health · doi:10.3389/fdgth.2025.1550407 · Cited by 31
Yu, J., Wu, X., Lv, M., Zhang, Y., Zhang, X., Li, J., Zhu, M., Huang, J., & Zhang, Q. (2020) · Oncology Letters · doi:10.3892/ol.2020.12250 · Cited by 29
Zhao, Z., Li, Y., Wu, Y., & Chen, R. (2019) · Cancer Biomarkers · doi:10.3233/cbm-190380 · Cited by 23
Federated transfer learning with differential privacy for multi-omics survival analysis
Wen, G., & Li, L. (2025) · Briefings in Bioinformatics · doi:10.1093/bib/bbaf166 · Cited by 17
Chen, S., Zang, Y., Xu, B., Lu, B., Ma, R., Miao, P., & Chen, B. (2022) · Computational and Mathematical Methods in Medicine · doi:10.1155/2022/5844846 · Cited by 15
Zhao, X., Xia, X., Wang, X., Bai, M., Zhan, D., & Shu, K. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.847706 · Cited by 10
Artificial Intelligence in Clinical Oncology: From Productivity Enhancement to Creative Discovery
Kuno, M., Osumi, H., Udagawa, S., Yoshikawa, K., Ooki, A., Shinozaki, E., Ishikawa, T., Oba, J., Yamaguchi, K., & Sakurada, K. (2025) · Current Oncology · doi:10.3390/curroncol32110588 · Cited by 7
Metadata
- Authors
- Chaudhary, K., Poirion, O. B., Lu, L., & Garmire, L. X.
- Affiliations
- University of Hawaii Cancer Center (US)
- University of Hawaiʻi at Mānoa (US)
- Corresponding author
- Garmire, Lana X.
- Venue
- Clinical Cancer Research
- Published
- 2018-03-14
- Volume
- 24
- Issue
- 6
- Pages
- 1248-1259
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC6050171
- OpenAlex
- W2951209146
- Cited by
- 1,091
- References
- 71
- Citations by year
- 2026: 95 · 2025: 135 · 2024: 159 · 2023: 152 · 2022: 152 · 2021: 171 · 2020: 124 · 2019: 71 · 2018: 28
- FWCI
- 38.36
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIEHS (K01ES025434)
- NIH/NIGMS (P20 COBRE GM103457)
- NICHD (R01 HD084633)
- NLM (R01LM012373)
- Hawaii Community Foundation (14ADVC-64566)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- hepatocellular carcinoma, survival prediction, prognosis, multi-omics integration, deep learning, RNA-seq, miRNA sequencing, DNA methylation, p53 inactivation, stem cell markers, Wnt signaling, Akt signaling, survivin, external validation, prognostic subgroups
- MeSH terms
- Deep Learning, Algorithms, Humans, Liver Neoplasms, Prognosis, Biomarkers, Tumor, Reproducibility of Results, Proportional Hazards Models, Computational Biology, Gene Expression Profiling, Genomics, Proteomics, Gene Regulatory Networks, Metabolomics, Transcriptome
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