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Reciprocal expression of the immune response genes CXCR3 and IFI44L as module hubs are associated with patient survivals in primary central nervous system lymphoma

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International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Here, we investigated expression modules reflecting the reciprocal expression of the cancer microenvironment and immune response-related genes associated with poor prognosis in primary central nervous system lymphoma (PCNSL).

Methods

Weighted gene coexpression network analysis revealed representative modules, including neurogenesis, immune response, anti-virus, microenvironment, gene expression and translation, extracellular matrix, morphogenesis, and cell adhesion in the transcriptome data of 31 PCNSL samples.

Results 

Gene expression networks were also reflected by protein–protein interaction networks. In particular, some of the hub genes were highly expressed in patients with PCNSL with prognoses as follows: AQP4, SLC1A3, GFAP, CXCL9, CXCL10, GBP2, IFI6, OAS2, IFIT3, DCN, LRP1, and LUM with good prognosis; and STAT1, IFITM3, GZMB, ISG15, LY6E, TGFB1, PLAUR, MMP4, FTH1, PLAU, CSF3R, FGR, POSTN, CCR7, TAS1R3, small ribosomal subunit genes, and collagen type 1/3/4/6 genes with poor prognosis. Furthermore, prognosis prediction formulae were constructed using the Cox proportional-hazards regression model, which demonstrated that the IP-10 receptor gene CXCR3 and type I interferon-induced protein gene IFI44L could predict patient survival in PCNSL.

Conclusion

These results indicate that the differential expression and balance of immune response and microenvironment genes may be required for PCNSL tumor growth or prognosis prediction, which would help understanding the mechanism of tumorigenesis and potential therapeutic targets in PCNSL.

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Availability of data and materials

Data and materials for the study are included in the manuscript and supplementary information.

Abbreviations

ABC:

Activated B cell

AUC:

Area under the curve

BBB:

Blood–brain barrier

CI:

Confidential interval

CNS:

Central nervous system

COL:

Collagen

DEGs:

Differentially expressed genes

DLBCL:

Diffuse large B cell lymphoma

EBV:

Epstein–Barr virus

ECM:

Extracellular matrix

FDR:

False discovery rate

FL:

Follicular lymphoma

FPKM:

Fragments per kilobase of exon per million reads mapped

GO:

Gene ontology

GSEA:

Gene set enrichment analysis

HD-MTX:

High-dose methotrexate

HR:

Hazard ratio

IELSG:

International Extranodal Lymphoma Study Group

KEGG:

Kyoto Encyclopedia of Genes and Genomes

KPS:

Karnofsky Performance Status

LDH:

Lactate dehydrogenase

MAD:

Mean absolute deviation

MCODE:

Molecular Complex Detection

MSKCC:

Memorial Sloan Kettering Cancer Center

NAFLD:

Non-alcoholic fatty liver disease

NGS:

Next generation sequencing

NHL:

Non-Hodgkin’s lymphoma

non-GCB:

Non-germinal center B cell-like

OS:

Overall survival

PCNSL:

Primary central nervous system lymphoma

PKA:

Protein kinase A

PPI:

Protein–protein interaction

PRPS:

Ribosomal subunits

ROC:

Receiver operating characteristic

SNV/indel:

Single nucleotide variant/insertion/deletion

STRING:

Search Tool of the Retrieval of Interacting Genes Database

WCNA:

Weighted correlation network analysis

WGCNA:

Weighted gene coexpression network analysis

WHO:

World Health Organization

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Acknowledgements

This study was supported in part by the MEXT KAKENHI Grant Number 21H03045 to RY. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funding

This study was supported in part by the MEXT KAKENHI Grant Number 21H03045 to RY. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

  1. Yasuo Takashima, Momoko Hamano and Kengo Yoshii contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Target Therapy for Cancer,, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan

    Yasuo Takashima, Azusa Hayano & Ryuya Yamanaka

  2. Department of Genomic Medical Sciences, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Yasuo Takashima

  3. Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Iizuka, Fukuoka, Japan

    Momoko Hamano

  4. Department of Mathematics and Statistics in Medical Sciences, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Kengo Yoshii

  5. Department of Neurological Surgery, Wakayama Medical University School of Medicine, Wakayama, Japan

    Junya Fukai

  6. Department of Neurosurgery, Graduate School of Medical Sciences, Chiba University, Chiba, Japan

    Yasuo Iwadate

  7. Department of Neurosurgery, Graduate School of Medical Sciences, Yamaguchi University, Ube, Yamaguchi, Japan

    Koji Kajiwara

  8. Department of Neurosurgery, Toyama Prefectural Central Hospital, Toyama, Japan

    Hiroaki Hondoh

Authors
  1. Yasuo Takashima
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  2. Momoko Hamano
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Contributions

YT and RY designed the experiments. JF, YI, KK and HH diagnosed and treated patients and collected samples. YT, MH, KY, AH and RY performed the experiments. YT, MH, KY, AH and RY analyzed data. YT and RY wrote the manuscript.

Corresponding author

Correspondence to Ryuya Yamanaka.

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The authors declare no competing interests.

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All experiments comply with the Ethics Committee of Kyoto Prefectural University of Medicine (RBMR-G-146).

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Takashima, Y., Hamano, M., Yoshii, K. et al. Reciprocal expression of the immune response genes CXCR3 and IFI44L as module hubs are associated with patient survivals in primary central nervous system lymphoma. Int J Clin Oncol 28, 468–481 (2023). https://doi.org/10.1007/s10147-022-02285-8

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  • DOI: https://doi.org/10.1007/s10147-022-02285-8

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