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Exploring prognostic value and regulation network of PPP1R1A in hepatocellular carcinoma

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Abstract

Novel and accurate biomarkers are needed for early detection and progression evaluation of hepatocellular carcinoma (HCC). Protein phosphatase 1 regulatory subunit 1A (PPP1R1A) has been studied in cancer biology; however, the expression pattern and biological function of PPP1R1A in HCC are unclear. The differentially expressed genes (DEGs) in HCC were screened by The Cancer Genome Atlas (TCGA) database. Real-time PCR and immunohistochemistry (IHC) assay were used to detect the expression of PPP1R1A in BALB/c mice, human normal tissues and corresponding tumor tissues, especially HCC. Then, Kaplan–Meier analysis of patients with HCC was performed to evaluate the relationship between PPP1R1A expression and prognosis. The transcriptional regulatory network of PPP1R1A was constructed based on the differentially expressed mRNAs, microRNAs and transcription factors (TFs). To explore the downstream regulation of PPP1R1A, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis and immune infiltration score were performed. A total of 4 DEGs were screened out. PPP1R1A was differentially distributed and expressed in BALB/c mice and human tissues. PPP1R1A expression was higher in normal tissues than that in tumor tissues, and patients with higher PPP1R1A expression had better clinical outcome in HCC. In addition, we constructed miR-21-3p/TAL1/PPP1R1A transcriptional network. Furthermore, PPP1R1A may modulate the activation of PI3K–Akt pathway, cell cycle, glycogen metabolism and the recruitment of M2 macrophage in HCC. This study may help to clarify the function and mechanism of PPP1R1A in HCC and provide a potential biomarker for tumor prevention and treatment.

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Data availability

All data is available under reasonable request.

Abbreviations

PPP1R1A:

Protein phosphatase 1 regulatory subunit 1A

PP1:

Protein phosphatase 1

PPP:

Phosphoprotein phosphatase

DEGs:

Differentially expressed genes

TCGA:

The Cancer Genome Atlas

TFs:

Transcription factors

GO:

Gene ontology

KEGG:

Kyoto encyclopedia of genes and genomes

PPI:

Protein–protein interaction

TCIA:

The cancer immunome atlas

OS:

Overall survival

DFS:

Disease-free survival

CCs:

Cellular components

MFs:

Molecular functions

BPs:

Biological processes

PKA:

Protein kinase A

IHC:

Immunohistochemistry

HCC:

Hepatocellular carcinoma

LIHC:

Liver hepatocellular carcinoma

BLCA:

Bladder urothelial carcinoma

COAD:

Colon adenocarcinoma

BRCA:

Breast invasive carcinoma

PAAD:

Pancreatic adenocarcinoma

LGG:

Brain lower grade glioma

KIRC:

Kidney renal clear cell carcinoma

UVM:

Uveal melanoma

ES:

Ewing sarcoma

TAM:

Tumor-associated macrophage

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Acknowledgements

Not applicable.

Funding

This work was supported by the President Foundation of Nanfang Hospital, Southern Medical University (NO. 2020C039); Clinical Research Startup Program of Southern Medical University (NO. LC2019ZD008); Clinical Research Program of Nanfang Hospital, Southern Medical University (NO. 2018CR021 and NO. 2020CR025); National Natural Science Foundation of China (NO. 82102839); China Postdoctoral Science Foundation (NO. 2020M682815); Guangdong Basic and Applied Basic Research Foundation (NO. 2020A1515110787).

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  1. Xixi Wu and Yin Wang have contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

    Xixi Wu, Yin Wang, Mi Yang, Yingqiao Wang, Xiaoqing Wang, Longshan Zhang, Liwei Liao, Nan Li, Mengyuan Mao, Jian Guan & Feng Ye

  2. Department of Radiation Oncology, Guangxi Zhuang Autonomous Region People’s Hospital, Nanning, Guangxi, China

    Xixi Wu

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  1. Xixi Wu
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Contributions

JG and FY: contributed to the study design and draft revision. MY, YQW and NL: contributed to human specimen collection. XXW, LWL and LSZ: contributed to implementation and analysis of real-time PCR and IHC assay. XQW, MYM and YW: contributed to mice and tissue preparation. XXW and YW: contributed to data collection and interpretation of bioinformatics results. XXW: contributed to draft the manuscript and coordinate data collection and analysis. All authors read and approved the final manuscript.

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Correspondence to Jian Guan or Feng Ye.

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The authors declare that there is no conflict of interests.

Ethical approval and informed consent

This study was approved by the Ethics Committee of Nanfang Hospital of Southern Medical University. All participants offered written informed consent before operation. The study conforms to the provisions of the Declaration of Helsinki. Generated Statement: no potentially identifiable human images or data is presented in this study. All animal experiments were performed according to the institutional guidelines and approved by the Nanfang hospital animal ethic committee on January 11, 2018, application number NFYY-2018-05.

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Supplementary Information

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13577_2022_771_MOESM1_ESM.tif

Figure S1 Biological distribution and expression analysis of PPP1R1A in human normal tissues using UCSC database. (TIF 1518 KB)

13577_2022_771_MOESM2_ESM.tif

Figure S2 Prognostic value of PPP1R1A in (A) pancreatic adenocarcinoma (PAAD), (B) brain lower grade glioma (LGG), (C) kidney renal clear cell carcinoma (KIRC) and (D) uveal melanoma (UVM). (TIF 1406 KB)

13577_2022_771_MOESM3_ESM.tif

Figure S3 Relationship between PRRX2 and PPP1R1A in HCC. A Expression of PRRX2 in HCC patients with MT or NMT based on TCGA database. B Pearson analysis of correlation between the expression of PRRX2 and PPP1R1A in HCC. (TIF 270 KB)

13577_2022_771_MOESM4_ESM.xls

Table S1 Expression of ten miRNAs with detailed transcriptional information in NMT group and MT group based on TCGA–LIHC database. NMT: without recurrence and metastasis in 3 years; MT: with recurrence and metastasis in 1 year. (XLS 61 KB)

13577_2022_771_MOESM5_ESM.xls

Table S2 Differential expression of transcription factors in NMT group compared with MT group according to TCGA–LIHC database. NMT: without recurrence and metastasis in 3 years; MT: with recurrence and metastasis in 1 year (XLS 64 KB)

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Wu, X., Wang, Y., Yang, M. et al. Exploring prognostic value and regulation network of PPP1R1A in hepatocellular carcinoma. Human Cell 35, 1856–1868 (2022). https://doi.org/10.1007/s13577-022-00771-9

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