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Journal of Cancer Research and Clinical Oncology

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31.10.2023 | Research

Establishment and validation of a novel lysosome-related gene signature for predicting prognosis and immune landscape in hepatocellular carcinoma

verfasst von: Haoling Li, Jing Li, Xiangyu Qu, Hengwen Dai, Junjie Liu, Mengxi Ma, Jian Wang, Wei Dong, Wenrui Wang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 19/2023

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Abstract

Background

Recent studies have shown that lysosomes not only provide energy for tumor cell growth, but also participate in the occurrence and development of malignant tumors by regulating various ways of tumor cell death. However, the role of lysosome associated genes (LSAGs) in hepatocellular carcinoma (HCC) remains unclear.

Methods

Transcriptome data and clinical data of HCC were downloaded from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. We identified differential expression of LSAGs by comparing tumor tissue with normal liver tissue. Subsequently, we used univariate COX analysis and least absolute shrinkage and selection operator (LASSO) COX regression to construct the prognostic feature of LSAGs. Kaplan–Meier survival curve and receiver operating characteristic curve were used to evaluate the predictive ability of LSAGs feature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for functional enrichment analysis of risk differential genes. The relationship between LSAGs score and tumor microenvironment and chemotherapy drug sensitivity was analyzed. Finally, the cellular communication of tumor cells with high and low expression of model LSAGs was explored.

Results

We identified sixteen prognostic associated LSAGs, four of which were selected to construct prognostic feature of LSAGs. Patients in the low LSAGs group had a better prognosis than those in the high LSAGs group. GO and KEGG analyses showed that risk differential genes were enriched in leukocyte migration, cytokine–cytokine receptor interaction and PI3K-Akt signaling pathway. The group with low LSAGs score had lower immune score. Patients in the high LSAGs group were more sensitive to drugs for chemotherapy. In addition, tumor cells with high expression of model LSAGs showed stronger association with immune cells through the interleukin-2 (IL2), fibroblast growth factor (FGF), adiponectin, and bone morphogenetic proteins (BMP) signaling pathways.

Conclusion

We established a LSAGs signature that had the ability to predict clinical prognosis and immune landscape, proposing potential therapeutic targets for HCC.

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Titel: Establishment and validation of a novel lysosome-related gene signature for predicting prognosis and immune landscape in hepatocellular carcinoma
verfasst von: Haoling Li
Jing Li
Xiangyu Qu
Hengwen Dai
Junjie Liu
Mengxi Ma
Jian Wang
Wei Dong
Wenrui Wang
Publikationsdatum: 31.10.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 19/2023
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-023-05477-5

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Establishment and validation of a novel lysosome-related gene signature for predicting prognosis and immune landscape in hepatocellular carcinoma

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