MCM team has been researching GSDMB


We continue our work on characterizing lung cancer biomarkers identified in the MCM1 project. This update focuses on GSDMB, a gene associated with lung cancer survival and differentially expressed across multiple cancer types compared to normal tissues.

Project: Mapping Cancer Markers

Published on: 12 Jul 2023

Background

Recognizing patterns in cancer patients can have many benefits, such as making it possible to detect signs of cancer in other patients and personalizing each patient’s treatment to fit their specific cancer profile. Since November 2013, World Community Grid volunteers have donated over 820,800 CPU years to the project, helping analyze research data on cancers and sarcomas at a speed never thought possible before. We are immensely grateful for the volunteers who continue to donate to this project, and help us accelerate the search for better biomarkers.

We continue our analysis of the most common biomarkers amongst lung cancer patients. Following discussion of the genes VAMP1 and FARP1 that were described in our March and April updates, here we focus on GSDMB.

GSDMB Research

Gasdermin B (GSDMB) is a protein in the GSDM family, which share similar structures and typically play roles in cell proliferation and differentiation[1]. The GSDM family are known for their role in triggering pyroptosis, a highly inflammatory type of cell death, which they accomplish by forming pores in cell membranes[1]. GSDMB has also been identified to regulate epithelial cell growth independently of its role in pyroptosis (Uniprot). GSDMB is considered unique among the other members of its family, and its role in various types of diseases and cancers is relatively under-studied. It has been shown that genetic variants in GSDMB are linked to increased susceptibility to diseases like asthma and inflammatory bowel disease (IBD)[2]. 

Similarly to VAMP1 and FARP1 genes, we investigated the role of GSDMB in lung cancer, and found that its presence has a protective role in lung cancer, as shown in Figure 1 (data from KMplotter).

Figure 1. Survival curves for patients with high and low expression of GSDMB.

Extending our observation beyond lung cancer, as it is an aim of our WCG project, we find that GSDMB behaves in a similar way in the majority of tested cancers, as visible in Figure 2. This suggests that GSDMB has an important role in carcinogenesis, and may play a role in hallmarks of cancer. This has been confirmed in the literature, where an association has been found between GSDMB expression levels and cancers such as gastric cancer, breast cancer[3], and bladder cancer[4].

Figure 2. Expression of GSDMB in normal and cancer tissues for multiple cancer types.

Using Human Protein Atlas (HPA), we also identified strong prognostic value of GSDMB protein, as shown in Figure 3.

Figure 3. Prognostic value of GSDMB protein in renal (unfavourable), urothelial and cervical cancers (favourable).

Exploring GSDMB expression using the GTEx portal (GTEx), we identify which cells in the lung express it, as shown in Figure 4.

Figure 4. Single cell data from the GTEx portal show strong expression both in epithelial and immune cells.

If you have any comments or questions, please leave them in this thread for us to answer. Thank you for your continued support.

WCG team

References:

  1. Li L, Li Y, Bai Y. Role of GSDMB in Pyroptosis and Cancer. Cancer Manag Res. 2020 Apr 30;12:3033-3043. doi: 10.2147/CMAR.S246948. PMID: 32431546; PMCID: PMC7201009.
  2. Rana N, Privitera G, Kondolf HC, Bulek K, Lechuga S, De Salvo C, Corridoni D, Antanaviciute A, Maywald RL, Hurtado AM, Zhao J, Huang EH, Li X, Chan ER, Simmons A, Bamias G, Abbott DW, Heaney JD, Ivanov AI, Pizarro TT. GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis. Cell. 2022 Jan 20;185(2):283-298.e17. doi: 10.1016/j.cell.2021.12.024. Epub 2022 Jan 11. PMID: 35021065; PMCID: PMC8879997.
  3. Xia X, Wang X, Cheng Z, Qin W, Lei L, Jiang J, Hu J. The role of pyroptosis in cancer: Pro-cancer or pro-“host”? Cell Death & Disease. 2019;10(9). doi:10.1038/s41419-019-1883-8. PMID: 31501419; PMCID: PMC6733901.
  4. He H, Yi L, Zhang B, Yan B, Xiao M, Ren J, Zi D, Zhu L, Zhong Z, Zhao X, Jin X, Xiong W. USP24-GSDMB complex promotes bladder cancer proliferation via activation of the STAT3 pathway. Int J Biol Sci. 2021 Jun 11;17(10):2417-2429. doi: 10.7150/ijbs.54442. PMID: 34326684; PMCID: PMC8315027.