Research update from the MCM team (November 2023)


We continue our work on characterizing lung cancer biomarkers identified in the MCM1 project. This update focuses on IL13RA1, a gene associated with lung cancer survival and differentially expressed across multiple cancer types compared to normal tissues.

Project: Mapping Cancer Markers

Published on: 27 Nov 2023

 

Background

Recognizing patterns in cancer patients can be beneficial, as it can allow us to detect signs of cancer in other patients or personalize different patients’ treatments to fit their genetic profiles. The Mapping Cancer Markers project analyzes databases with millions of data points collected from patients with cancers and sarcomas to find such diagnostic, prognostic and predictive signatures.

Since November 2013, World Community Grid volunteers have donated over 867,200 CPU years to the project, helping analyze research data on different cancer types at a significantly faster pace and more thoroughly than otherwise possible. We are immensely grateful for the volunteers who continue to donate to this project.

We continue our work on common lung cancer biomarkers. VAMP1, FARP1, GSDMB, and ADH6 were discussed in our March, April, July, and September updates. Here, we outline information on IL13RA1.

IL13RA1 Research

IL13RA1, part of the interleukin receptor family, encodes interleukin-13 receptor subunit alpha-1, which, together with IL4RA, forms a functional receptor for interleukin-13 (IL13) (Uniprot). Interleukins are a type of cytokines that are expressed by a variety of body cells and play integral roles in immune cell activation and differentiation, as well as proliferation, maturation, migration, and adhesion. Therefore, as a subunit of an IL13 receptor, IL13RA1 enables IL13 to exert these effects. 

Given its involvement in immune function, it is not surprising that a possible link has been identified between IL13RA1 and several diseases, including coronary heart disease[1], Parkinson’s disease[2], ulcerative colitis[3], asthma and other allergic diseases[4,5,6]. IL13RA1 has also been identified as a synaptic protein that is implicated in plasticity and neuroprotection following injury[7].

In line with the other genes we have presented, we investigated the role of IL13RA1 in lung cancer, finding that it has a protective role, as shown in Figure 1.

Figure 1. Survival curves for patients with high and low expression of IL13RA1 (KMplotter).

We also investigated whether this finding extends to other cancers. As shown in Figure 2, similar trends in IL13RA1 expression are seen across the majority of tested cancers. In line with this observation, within the literature, associations have been documented between IL13RA1 expression and pancreatic cancer[8], thyroid cancer[9], bladder cancer[10], breast cancer[11] and brain cancer[12].

Figure 2. Expression of IL13RA1 in normal and cancer tissue for multiple cancer types. Red text represents a significant difference between expression in cancer tissue compared with normal tissue (TNMplot).

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. Feng X, Zhang Y, Du M, Li S, Ding J, Wang J, Wang Y, Liu P. Identification of diagnostic biomarkers and therapeutic targets in peripheral immune landscape from coronary artery disease. J Transl Med. 2022 Sep 5;20(1):399. doi: 10.1186/s12967-022-03614-1. PMID: 36064568; PMCID: PMC9444127.
  2. Aguirre CA, Concetta Morale M, Peng Q, Sanchez-Alavez M, Cintrón-Colón R, Feng K, Fazelpour S, Maher P, Conti B. Two single nucleotide polymorphisms in IL13 and IL13RA1 from individuals with idiopathic Parkinson's disease increase cellular susceptibility to oxidative stress. Brain Behav Immun. 2020 Aug;88:920-924. doi: 10.1016/j.bbi.2020.04.007. Epub 2020 Apr 7. PMID: 32276028; PMCID: PMC9012133.
  3. Gwiggner M, Martinez-Nunez RT, Whiteoak SR, Bondanese VP, Claridge A, Collins JE, Cummings JRF, Sanchez-Elsner T. MicroRNA-31 and MicroRNA-155 Are Overexpressed in Ulcerative Colitis and Regulate IL-13 Signaling by Targeting Interleukin 13 Receptor α-1. Genes (Basel). 2018 Feb 13;9(2):85. doi: 10.3390/genes9020085. PMID: 29438285; PMCID: PMC5852581.
  4. Konstantinidis AK, Barton SJ, Sayers I, Yang IA, Lordan JL, Rorke S, Clough JB, Holgate ST, Holloway JW. Genetic association studies of interleukin-13 receptor alpha1 subunit gene polymorphisms in asthma and atopy. Eur Respir J. 2007 Jul;30(1):40-7. doi: 10.1183/09031936.00025706. Epub 2007 Mar 28. PMID: 17392323.
  5. Furue M, Ulzii D, Nakahara T, Tsuji G, Furue K, Hashimoto-Hachiya A, Kido-Nakahara M. Implications of IL-13Rα2 in atopic skin inflammation. Allergol Int. 2020 Jul;69(3):412-416. doi: 10.1016/j.alit.2020.01.005. Epub 2020 Feb 6. PMID: 32037147.
  6. McKenzie CI, Varese N, Aui PM, Reinwald S, Wines BD, Hogarth PM, Thien F, Hew M, Rolland JM, O'Hehir RE, van Zelm MC. RNA sequencing of single allergen-specific memory B cells after grass pollen immunotherapy: Two unique cell fates and CD29 as a biomarker for treatment effect. Allergy. 2023 Mar;78(3):822-835. doi: 10.1111/all.15529. Epub 2022 Oct 1. PMID: 36153670.
  7. Li S, Olde Heuvel F, Rehman R, Aousji O, Froehlich A, Li Z, Jark R, Zhang W, Conquest A, Woelfle S, Schoen M, O Meara CC, Reinhardt RL, Voehringer D, Kassubek J, Ludolph A, Huber-Lang M, Knöll B, Morganti-Kossmann MC, Brockmann MM, Boeckers T, Roselli F. Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection. Nat Commun. 2023 Jan 13;14(1):200. doi: 10.1038/s41467-023-35806-8. PMID: 36639371; PMCID: PMC9839781.
  8. Shi J, Shen X, Kang Q, Yang X, Denzinger M, Kornmann M, Traub B. Loss of Interleukin-13-Receptor-Alpha-1 Induces Apoptosis and Promotes EMT in Pancreatic Cancer. Int J Mol Sci. 2022 Mar 26;23(7):3659. doi: 10.3390/ijms23073659. PMID: 35409019; PMCID: PMC8998778.
  9. Wang B, Shen W, Yan L, Li X, Zhang L, Zhao S, Jin X. Reveal the potential molecular mechanism of circRNA regulating immune-related mRNA through sponge miRNA in the occurrence and immune regulation of papillary thyroid cancer. Ann Med. 2023;55(2):2244515. doi: 10.1080/07853890.2023.2244515. PMID: 37603701; PMCID: PMC1044398.
  10. Fang ZQ, Zang WD, Chen R, Ye BW, Wang XW, Yi SH, Chen W, He F, Ye G. Gene expression profile and enrichment pathways in different stages of bladder cancer. Genet Mol Res. 2013 May 6;12(2):1479-89. doi: 10.4238/2013.May.6.1. PMID: 23765955.
  11. He M, Hu C, Deng J, Ji H, Tian W. Identification of a novel glycolysis-related signature to predict the prognosis of patients with breast cancer. World J Surg Oncol. 2021 Oct 2;19(1):294. doi: 10.1186/s12957-021-02409-w. PMID: 34600547; PMCID: PMC8487479.
  12. Moreno DA, da Silva LS, Gomes I, Leal LF, Berardinelli GN, Gonçalves GM, Pereira CA, Santana IVV, Matsushita MM, Bhat K, Lawler S, Reis RM. Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients' survival. Ther Adv Med Oncol. 2022 Dec 21;14:17588359221127678. doi: 10.1177/17588359221127678. PMID: 36579028; PMCID: PMC9791289.