Inverse Correlation Between NLRP3 and TMEM176B As a Possible Tool for Colorectal Cancer Progression

Purpose: TMEM176B has been recently identified as a novel player in anti-cancer immune responses by negatively modulating the NLRP3 inflammasome activation in colorectal cancer (CRC). Yet, the TMEM176B/NLRP3 axis in CRC needs to be deeply investigated. Methods: TMEM176B and NLRP3 expression were evaluated in CRC patients by immunohistochemistry and RT-qPCR assays. The prognostic relevance of TMEM176B and NLRP3 was determined by in silico analysis. The NLRP3 inflammasome activation in the CRC microenvironment was assessed in a peripheral blood mononuclear cells (PBMC) and CRC cell line (HCT-116) spheroids co-culture assay. Results: Reduced NLRP3 and increased TMEM176B expression correlates to CRC stages and poor survival. The in vitro assay showed HCT-116 cells activated NLRP3 inflammasome in PBMC. Conclusion: These findings evidence the inverse correlation between NLRP3 and TMEM176B in CRC progression, suggesting them as a predictive tool. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Sao Paulo State Research Foundation (FAPESP) grant number 2019/06363-4 (A.P.) and 2021/0540-4 (A.P.). Authors are supported by fellowship programs: Excellence in research Fellowship from National Council for Scientific and Technological Development (CNPq) (A.P.); Post-doctoral fellowship from FAPESP (process n. 2020/15323-3) (V.N.C.L.); CAPES PhD Fellowship (R.A.G.C.; M.E.G.V.R.). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ethics Committee of ICB/USP (CEPSH) (process number 30173919.1.0000.5467) approved the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors