Expression and clinical value of NLRP1 and NLRC4 inflammasomes in prostate cancer

Liang,Ke; Ke,Zunjin; Huang,Jianhong; Zhang,Xijiong

doi:10.3892/ol.2023.13971

Expression and clinical value of NLRP1 and NLRC4 inflammasomes in prostate cancer

Authors:
- Ke Liang
- Zunjin Ke
- Jianhong Huang
- Xijiong Zhang
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Affiliations: Department of Urology, The First People's Hospital of Pinghu, Pinghu, Zhejiang 314200, P.R. China, Department of Urology, The First People's Hospital of Pinghu, Pinghu, Zhejiang 314200, P.R. China, Department of Pathology, The First People's Hospital of Pinghu, Pinghu, Zhejiang 314200, P.R. China
Published online on: July 20, 2023 https://doi.org/10.3892/ol.2023.13971
Article Number: 385
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study explored the clinical value of the protein expression levels of nucleotide binding oligomerization‑like receptor family pyrin domain containing 1 (NLRP1) and nucleotide‑binding oligomerization domain leucine‑rich repeat and caspase recruitment domain‑containing 4 (NLRC4) inflammasomes in the diagnosis and treatment of prostate cancer. A total of 54 patients with prostatic hyperplasia and 58 patients with prostate cancer were recruited at The First People's Hospital of Pinghu between January and May 2022. Immunohistochemical staining was used to determine the protein expression levels of the NLRP1 and NLRC4 inflammasomes in addition to the proinflammatory cytokines IL‑18 and IL‑1β in the two groups of patients. The protein expression levels of NLRP1 and NLRC4 inflammasome were significantly increased in patients with prostate cancer compared with patients with prostate hyperplasia. The differences in expression of NLRP1 and NLRC4 inflammatory vesicles in prostate cancer of different stages were also compared based on data from The Cancer Genome Atlas. The protein expression level of NLRP1 demonstrated a significant positive correlation with IL‑1β and IL‑18 expression, and the protein expression level of the NLRC4 inflammasome was significantly positively correlated with IL‑18 expression. The protein expression levels of both NLRP1 and NLRC4 demonstrated a significant positive correlation with the Gleason score of prostate cancer. The expression of NLRP1 in tumor (T)3/T4 was significantly higher compared with T1 and expression of the NLRC4 inflammasome in T2 and T3/T4 was significantly higher compared with T1. Expression of the NLRP1 and NLRC4 inflammasomes was significantly higher in patients with prostate cancer, compared with patients with prostatic hyperplasia. Therefore, expression of NLRP1 and NLRC4 may promote tumorigenesis by promoting the maturation and release of proinflammatory cytokines IL‑1β and IL‑18. Expression of the NLRP1 and NLRC4 inflammasomes demonstrated a significant positive correlation with the risk of prostate cancer. Expression of the NLRP1 and NLRC4 inflammasomes in middle‑ and advanced‑stage tumors was higher compared with early‑stage tumors. These results suggested that inflammasome expression may serve a significant role in the progression of tumors and could provide a fixed value for the risk assessment and prognosis prediction of prostate cancer.

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1	Boehm BJ, Colopy SA, Jerde TJ, Loftus CJ and Bushman W: Acute bacterial inflammation of the mouse prostate. Prostate. 72:307–317. 2012. View Article : Google Scholar : PubMed/NCBI
2	Guo YL, Na YQ, Ye ZQ and Huang J: Guidelines for Diagnosis and Treatment of Urology and Andrology Diseases in China. Science Press; Beijing, China: pp. pp4392019
3	Xie Jinbo and Peng Bo: Research progress on the epidemiological characteristics and risk factors of benign prostatic hyperplasia. J Tongji Univ Med Edition. 42:62021.(In Chinese).
4	Leela SCA, Paes Batista da Silva A, Verma S, Fu P, Shen DL, MacLennan G, Gupta S and Bissada NF: Presence of specific periodontal pathogens in prostate gland diagnosed with chronic inflammation and adenocarcinoma. Cureus. 13:e177422021.PubMed/NCBI
5	Gurel B, Lucia MS, Thompson IM Jr, Goodman PJ, Tangen CM, Kristal AR, Parnes HL, Hoque A, Lippman SM, Sutcliffe S, et al: Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev. 23:847–856. 2014. View Article : Google Scholar : PubMed/NCBI
6	Mishra V and Pathak C: Human Toll-Like Receptor 4 (hTLR4): Structural and functional dynamics in cancer. Int J Biol Macromol. 122:425–451. 2019. View Article : Google Scholar : PubMed/NCBI
7	Krysko DV, Agostinis P, Krysko O, Garg AD, Bachert C, Lambrecht BN and Vandenabeele P: Emerging role of damage-associated molecular patterns derived from mitochondyria in inflammation. Trends Immunol. 32:157–164. 2011. View Article : Google Scholar : PubMed/NCBI
8	Costa FRC, Leite JA, Rassi DM, da Silva JF, Elias-Oliveira J, Guimarães JB, Foss-Freitas MC, Câmara NOS, Pontillo A, Tostes RC, et al: NLRP1 acts as a negative regulator of Th17 cell programming in mice and humans with autoimmune diabetes. Cell Rep. 35:1091762021. View Article : Google Scholar : PubMed/NCBI
9	Alehashemi S and Goldbach-Mansky R: Human autoinflammatory diseases mediated by NLRP3-, Pyrin-, NLRP1-, and NLRC4-Inflammasome dysregulation updates on diagnosis, treatment, and the respective roles of IL-1 and IL-18. Front Immunol. 11:18402020. View Article : Google Scholar : PubMed/NCBI
10	Moecking J, Laohamonthonkul P, Chalker K, White MJ, Harapas CR, Yu CH, Davidson S, Hrovat-Schaale K, Hu D, Eng C, et al: NLRP1 variant M1184V decreases inflammasome activation in the context of DPP9 inhibition and asthma severity. J Allergy Clin Immunol. 147:2134–2145.e20. 2021. View Article : Google Scholar : PubMed/NCBI
11	Ciążyńska M, Olejniczak-Staruch I, Sobolewska-Sztychny D, Narbutt J, Skibińska M and Lesiak A: The role of NLRP1, NLRP3, and AIM2 inflammasomes in psoriasis: Review. Int J Mol Sci. 22:58982021. View Article : Google Scholar : PubMed/NCBI
12	Huang T, Yin H, Ning W, Wang X, Chen C, Lin W, Li J, Zhou Y, Peng Y, Wang M, et al: Expression of inflammasomes NLRP1, NLRP3 and AIM2 in different pathologic classification of lupus nephritis. Clin Exp Rheumatol. 38:680–690. 2020.PubMed/NCBI
13	Gong Q, Robinson K, Xu C, Huynh PT, Chong KHC, Tan EYJ, Zhang J, Boo ZZ, Teo DET, Lay K, et al: Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8. Nat Commun. 12:1882021. View Article : Google Scholar : PubMed/NCBI
14	Zhang J, Pei L, Zang D, Xue Y, Wang X, Chen Y, Li J, Yu J, Gao Q, Di W, et al: Gender differences of NLRP1 inflammasome in mouse model of Alzheimer's disease. Front Aging Neurosci. 12:5120972020. View Article : Google Scholar : PubMed/NCBI
15	Karki R and Kanneganti TD: Diverging inflammasome signals in tumorigenesis and potential targeting. Nat Rev Cancer. 19:197–214. 2019. View Article : Google Scholar : PubMed/NCBI
16	Gouravani M, Khalili N, Razi S, Keshavarz-Fathi M, Khalili N and Rezaei N: The NLRP3 inflammasome: A therapeutic target for inflammation-associated cancers. Expert Rev Clin Immunol. 16:175–187. 2020. View Article : Google Scholar : PubMed/NCBI
17	Sundaram B and Kanneganti TD: Advances in understanding activation and function of the NLRC4 inflammasome. Int J Mol Sci. 22:10482021. View Article : Google Scholar : PubMed/NCBI
18	Broz P: Recognition of intracellular bacteria by inflammasomes. Microbiol Spectr. 7:2019. View Article : Google Scholar : PubMed/NCBI
19	Chear CT, Nallusamy R, Canna SW, Chan KC, Baharin MF, Hishamshah M, Ghani H, Ripen AM and Mohamad SB: A novel de novo NLRC4 mutation reinforces the likely pathogenicity of specific LRR domain mutation. Clin Immunol. 211:1083282020. View Article : Google Scholar : PubMed/NCBI
20	Yang J, Gu J, Hu Y, Wang N, Gao J and Wang P: Molecular cloning and characterization of HSP60 gene in domestic pigeons (Columba livia) and differential expression patterns under temperature stress. Cell Stress Chaperones. 26:115–127. 2021. View Article : Google Scholar : PubMed/NCBI
21	Barry MJ, Fowler FJ jr, O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK and Cockett AT: The American Urological Association symptom index for benign prostatic hyperplasia The Measurement Committee of the American Urological Association. J Urol. 148:1549–1557; discussion 1564. 1992. View Article : Google Scholar : PubMed/NCBI
22	Chen YJ, Luo SN, Dong L, Liu TT, Shen XZ, Zhang NP and Liang L: Interferon regulatory factor family influences tumor immunity and prognosis of patients with colorectal cancer. J Transl Med. 19:3792021. View Article : Google Scholar : PubMed/NCBI
23	Zhou T, Cai Z, Ma N, Xie W, Gao C, Huang M, Bai Y, Ni Y and Tang Y: A novel ten-gene signature predicting prognosis in hepatocellular carcinoma. Front Cell Dev Biol. 8:6292020. View Article : Google Scholar : PubMed/NCBI
24	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I and Jemal Aand Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
25	Cao W, Chen HD, Yu YW, Li N and Chen WQ: Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 134:783–791. 2021. View Article : Google Scholar : PubMed/NCBI
26	Puhr M, De Marzo A, Isaacs W, Lucia MS, Sfanos K, Yegnasubramanian S and Culig Z: Inflammation, microbiota, and prostate cancer. Eur Urol Focus. 2:374–382. 2016. View Article : Google Scholar : PubMed/NCBI
27	Ohashi K, Wang Z, Yang YM, Billet S, Tu W, Pimienta M, Cassel SL, Pandol SJ, Lu SC, Sutterwala FS, et al: NOD-like receptor C4 inflammasome regulates the growth of colon cancer liver metastasis in NAFLD. Hepatology. 70:1582–1599. 2019. View Article : Google Scholar : PubMed/NCBI
28	Schillaci O, Scimeca M, Trivigno D, Chiaravalloti A, Facchetti S, Anemona L, Bonfiglio R, Santeusanio G, Tancredi V, Bonanno E, et al: Prostate cancer and inflammation: A new molecular imaging challenge in the era of personalized medicine. Nucl Med Biol. 68–69. 66–69. 2019.
29	Yu CH, Moecking J, Geyer M and Masters SL: Mechanisms of NLRP1-mediated autoinflammatory disease in humans and Mice. J Mol Biol. 430:142–152. 2018. View Article : Google Scholar : PubMed/NCBI
30	Fan Y, Yang L, Wei Q, Ding Y, Tang Z, Tan P, Lin T, Guo D and Qiu S: Toll-like receptor 10 (TLR10) exhibits suppressive effects on inflammation of prostate epithelial cells. Asian J Androl. 21:393–399. 2019. View Article : Google Scholar : PubMed/NCBI
31	Kashyap M, Pore S, Wang Z, Gingrich J, Yoshimura N and Tyagi P: Inflammasomes are important mediators of prostatic inflammation associated with BPH. J Inflamm (Lond). 12:372015. View Article : Google Scholar : PubMed/NCBI
32	Glinskii AB, Ma S, Ma J, Grant D, Lim CU, Guest I, Sell S, Buttyan R and Glinsky GV: Networks of intergenic long-range enhancers and snpRNAs drive castration-resistant phenotype of prostate cancer and contribute to pathogenesis of multiple common human disorders. Cell Cycle. 10:3571–3597. 2011. View Article : Google Scholar : PubMed/NCBI
33	Wen J, Xuan B, Liu Y, Wang L, He L, Meng X, Zhou T and Wang Y: Updating the NLRC4 inflammasome: From bacterial infections to autoimmunity and cancer. Front Immunol. 12:7025272021. View Article : Google Scholar : PubMed/NCBI
34	Li Y, Fu TM, Lu A, Witt K, Ruan J, Shen C and Wu H: Inaugural Article: Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1. Proc Natl Acad Sci USA. 115:10845–10852. 2018. View Article : Google Scholar : PubMed/NCBI
35	Man SM, Tourlomousis P, Hopkins L, Monie TP, Fitzgerald KA and Bryant CE: Salmonella infection induces recruitment of caspase-8 to the inflammasome to modulate IL-1β production. J Immunol. 191:5239–5246. 2013. View Article : Google Scholar : PubMed/NCBI
36	Dupaul-Chicoine J, Arabzadeh A, Dagenais M, Douglas T, Champagne C, Morizot A, Rodrigue-Gervais IG, Breton V, Colpitts SL, Beauchemin N and Saleh M: The Nlrp3 inflammasome suppresses colorectal cancer metastatic growth in the liver by promoting natural killer cell tumoricidal activity. Immunity. 43:751–763. 2015. View Article : Google Scholar : PubMed/NCBI
37	Lv Y, Ruan G, Liu Y, Cui D, Zhao Y, Yan C, Lv M, Xu D, Mao Y, Cao J, et al: Aberrant expression of NLRP3,NLRC4 and NLRP6 inflammasomes in patients with primary im-mune thrombocytopenia. Thromb Res. 176:101–103. 2019. View Article : Google Scholar : PubMed/NCBI
38	Di Donato M, Giovannelli P, Cernera G, Di anti A, Marino I, Bilancio A, Galasso G, Auricchio F, Migliaccio A and Castoria G: Non-genomic androgen action regulates proliferative/migratory signaling in stromal cells. Front Endocrinol (Lausanne). 5:2252014.PubMed/NCBI
39	Van den Brule FA, Waltregny D and Castronovo V: Increased expression of galectin-1 in carcinoma-associated stroma predicts poor outcome in prostate carcinoma patients. J Pathol. 193:80–87. 2001. View Article : Google Scholar : PubMed/NCBI
40	Dai J, Lu Y, Roca H, Keller JM, Zhang J, McCauley LK and Keller ET: Immune mediators in the tumor microenvironment of prostate cancer. Chin J Cancer. 36:292017. View Article : Google Scholar : PubMed/NCBI
41	Jiang H, He H, Chen Y, Huang W, Cheng J, Ye J, Wang A, Tao J, Wang C, Liu Q, et al: Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders. J Exp Med. 214:3219–3238. 2017. View Article : Google Scholar : PubMed/NCBI
42	Huang Y, Jiang H, Chen Y, Wang X, Yang Y, Tao J, Deng X, Liang G, Zhang H, Jiang W and Zhou R: Tranilast directly targets NLRP3 to treat inflammasome-driven diseases. EMBO Mol Med. 10:e86892018. View Article : Google Scholar : PubMed/NCBI