Immune checkpoint gene VSIR predicts patient prognosis in acute myeloid leukemia and myelodysplastic syndromes

Our plain-English summary of Immune checkpoint gene VSIR predicts patient prognosis in acute myeloid leukemia and myelodysplastic syndromes, by K. Yao, E. Zhou, E. Schaafsma, et al (Cancer Medicine, 2023).

The study

• Authors: K. Yao, E. Zhou, E. Schaafsma, B. Zhang, C. Cheng
• Journal: Cancer Medicine
• Published: 2023;12(5):5590-5602
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Immune checkpoint proteins play critical functions during the immune response to cancer and have been targeted by immune checkpoint blockade therapy. V-domain Ig suppressor of T cell activation (VSIR) is one of these immune checkpoint genes and has been investigated extensively in recent years due to its conflicting roles in cancer immunity. Specifically, in acute myeloid leukemia (AML), the prognostic value of VSIR is debated.

Results: In both patient tumor samples and cancer cell lines we find that VSIR has the highest expression in AML out of all cancer types and, in AML, has the highest expression out of all other immune checkpoint genes. Survival analysis indicated that AML patients with higher VSIR expression have significantly shorter survival than those patients with lower expression, even within established AML subgroups (e.g., FAB subtypes). Importantly, VSIR expression is predictive of progression from myelodysplastic syndromes (MDS) patients into AML, suggesting its potential role during the very early stage of AML development and progression. In addition to AML, VSIR also demonstrates prognostic values in other cancer types, including multiple myeloma and mesothelioma.

Conclusion: In summary, our analyses revealed the prognostic value of VSIR and its potential as a target for immunotherapy, especially in AML.

© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

In plain English

This study was a computer analysis of existing, publicly available gene-expression datasets. The authors measured how active an immune checkpoint gene called VSIR was in tumor samples and cell lines. The main focus was acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), a condition that can progress to AML. In AML patients from The Cancer Genome Atlas, those with higher-than-median VSIR expression had a median survival of 273 days, compared with 471 days for those with lower expression. In a second AML dataset of 526 samples, higher VSIR expression was also linked to worse survival (p = 0.004). In MDS patients, higher VSIR expression was associated with shorter overall survival and with a higher risk of progressing to AML (p = 0.02 after adjusting for age, gender and cytogenetic risk). In mesothelioma the direction was reversed: low VSIR expression was associated with poorer prognosis (p = 2 e-4, as printed in the article). The article did not give the type of mesothelioma or the number of patients. The authors concluded that VSIR is a poor prognostic factor for overall survival in AML and MDS. They named the lack of large datasets as a limitation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Computational (bioinformatic) analysis of existing public gene-expression, mutation and survival datasets
• Who was studied: Public datasets: TCGA AML samples (173 with expression data), cancer cell lines from CCLE, a de novo AML dataset (GSE14468, 526 samples), an MDS dataset (159 MDS and 17 wild-type samples), single-cell data from 16 AML patients and five healthy donors, PRECOG datasets for seven blood cancer types, and TCGA data for other cancer types including mesothelioma (number of mesothelioma patients not given)
• Exposure: No asbestos or fiber exposure was studied. The factor examined was the expression level of the VSIR immune checkpoint gene, split into high and low groups at the median.
• Main results:
  • TCGA AML patients: median survival of 273 days in the high-VSIR group versus 471 days in the low-VSIR group
  • Independent AML dataset (GSE14468, n = 526): patients with high VSIR expression had significantly worse prognosis (p = 0.004)
  • Within AML FAB subtypes, high VSIR expression was associated with poor prognosis in M1 (p = 0.05), M2 (p = 0.001) and M4 (p = 0.01). The association was not significant in the other subtypes.
  • MDS patients: VSIR expression was associated with overall survival (univariate p = 0.008; multivariate p = 0.02)
  • MDS patients: higher VSIR expression was associated with higher risk of progression to AML (univariate p = 0.05; p = 0.02 after adjusting for age, gender and cytogenetic risk)
  • Mesothelioma (TCGA MESO): low VSIR expression was associated with poor prognosis (p = 2 e-4). The same reverse pattern was seen in cervical squamous cell carcinoma (p = 0.03).
  • Multiple myeloma and CLL: low VSIR expression was associated with poor prognosis (multiple myeloma p = 2 e-6; CLL p = 8 e-4)
• The authors' conclusion: The authors concluded that VSIR is a poor prognostic factor for overall survival in AML and MDS. They also suggested that VSIR blockade therapy may be a promising treatment for MDS patients.
• Limitations the authors state:
  • Lack of large datasets with VSIR expression data for AML patients
  • Only gene expression was measured, not protein, and gene expression may correlate poorly with protein levels
  • The finding that VSIR may be prognostic only in patients without the NPM1 mutation needs validation in a larger dataset

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Myeloma, Mesothelioma, Immunotherapy.

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