Integrating single-cell and bulk sequencing data to identify glycosylation-based genes in non-alcoholic fatty liver disease-associated hepatocellular carcinoma

Author:

Zhou Zhijia1,Gao Yanan2,Deng Longxin2,Lu Xiaole2,Lai Yancheng2,Wu Jieke2,Chen Shaodong3,Li Chengzhong4,Liang Huiqing56

Affiliation:

1. Department of Hepatology, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China

2. The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China

3. Xiamen University, Xiamen, Fujian Province, China

4. Changhai Hospital, The Second Military Medical University, Shanghai, China

5. Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian Province, China

6. College of Traditional Chinese Medicine, Beijing University of Traditional Chinese Medicine, Beijing, China

Abstract

Background The incidence of non-alcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) has been increasing. However, the role of glycosylation, an important modification that alters cellular differentiation and immune regulation, in the progression of NAFLD to HCC is rare. Methods We used the NAFLD-HCC single-cell dataset to identify variation in the expression of glycosylation patterns between different cells and used the HCC bulk dataset to establish a link between these variations and the prognosis of HCC patients. Then, machine learning algorithms were used to identify those glycosylation-related signatures with prognostic significance and to construct a model for predicting the prognosis of HCC patients. Moreover, it was validated in high-fat diet-induced mice and clinical cohorts. Results The NAFLD-HCC Glycogene Risk Model (NHGRM) signature included the following genes: SPP1, SOCS2, SAPCD2, S100A9, RAMP3, and CSAD. The higher NHGRM scores were associated with a poorer prognosis, stronger immune-related features, immune cell infiltration and immunity scores. Animal experiments, external and clinical cohorts confirmed the expression of these genes. Conclusion The genetic signature we identified may serve as a potential indicator of survival in patients with NAFLD-HCC and provide new perspectives for elucidating the role of glycosylation-related signatures in this pathologic process.

Funder

National Science Natural Foundation of China

Publisher

PeerJ

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