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. 2022 Feb 15:15:1063-1077.
doi: 10.2147/JIR.S350609. eCollection 2022.

Elevated ALCAM Expression Associated with Endotypes and Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps

Hua Zhang #  1   2   3 , Shaobing Xie #  1   2   3 , Ruohao Fan  1   2   3 , Fengjun Wang  1   2   3 , Zhihai Xie  1   2   3 , Weihong Jiang  1   2   3
Affiliations

Elevated ALCAM Expression Associated with Endotypes and Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps

Hua Zhang et al. J Inflamm Res. .

Abstract

Background: Chronic rhinosinusitis with polyps (CRSwNP) is characterized by high heterogeneity and postoperative recurrence rate. This study aimed to explore the clinical significance of activated leukocyte cell adhesion molecule (ALCAM) in endotyping CRSwNP and predicting its recurrence.

Methods: We recruited 120 CRSwNP patients including 70 non-eosinophilic CRSwNP (neCRSwNP) and 50 eosinophilic CRSwNP (eCRSwNP) patients, and 40 healthy controls (HCs). Serum and tissue samples were collected. Serum ALCAM levels were detected by enzyme-linked immunosorbent assay (ELISA), and tissue ALCAM expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and immunohistochemistry (IHC). The predictive values of ALCAM expression for CRSwNP endotypes and postoperative recurrence were assessed.

Results: The serum levels of ALCAM were significantly increased in CRSwNP patients in comparison with HCs and were correlated with the peripheral eosinophil count, tissue eosinophil counts, and percentage. Multivariate analysis and receiver operating characteristic (ROC) curve highlighted that serum ALCAM levels were associated with CRSwNP endotypes. Tissue ALCAM expression was significantly enhanced in CRSwNP patients, especially in eCRSwNP patients. At the end of the study, 110 patients completed the follow-up schedule, 78 patients were categorized into the non-recurrent group, and the other 32 patients were included in the recurrent group. The serum ALCAM levels were elevated in the recurrent group compared with the non-recurrent group, and ALCAM expression in the tissue was significantly elevated. The ROC curve exhibited a high predictive ability of serum ALCAM in predicting postoperative recurrence. Logistic regression and Kaplan-Meier curves demonstrated that serum ALCAM was an independent risk factor for postoperative recurrence.

Conclusion: This is the first report suggesting that ALCAM expression was upregulated and associated with mucosal eosinophil infiltration and CRSwNP recurrence. Serum ALCAM could be a promising biomarker for distinguishing endotypes and predicting postoperative recurrence in CRwNP patients.

Keywords: activated leukocyte cell adhesion molecule; biomarker; chronic rhinosinusitis with nasal polyps; endotypes; recurrence.

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Conflict of interest statement

The authors declare no conflict of interest in preparing this article.

Figures

Figure 1
Figure 1
Comparison of serum ALCAM levels between CRSwNP patients and HCs. (A) ALCAM levels were significantly elevated in the CRSwNP group than the HC group. (B) Serum ALCAM levels were markedly enhanced in the eCRSwNP group than the neCRSwNP and HC groups.
Figure 2
Figure 2
The ROC curves of potentially predictive biomarkers for discriminating eCRSwNP. (A) serum ALCAM; (B) peripheral eosinophil percentage.
Figure 3
Figure 3
The serum ALCAM levels in the non-recurrent CRSwNP patients and the recurrent CRSwNP patients. (A) Serum ALCAM concentrations were elevated in the recurrent CRSwNP group than the non-recurrent CRSwNP group. (B) Serum ALCAM levels were significantly enhanced in the recurrent eCRSwNP group than the non-recurrent eCRSwNP and non-recurrent neCRSwNP groups.
Figure 4
Figure 4
The ROC curve (A) and Kaplan-Meier survival analysis (B) for serum ALCAM level in the prediction of CRSwNP recurrence.
Figure 5
Figure 5
Comparison of ALCAM mRNA levels in the tissue of CRSwNP patients and HCs. (A) ALCAM mRNA expressions were elevated in the CRSwNP group than the HC group. (B) ALCAM mRNA levels were significantly increased in the eCRSwNP group than the neCRSwNP group. (C) no significant difference was observed in mRNA levels between the non-recurrent CRSwNP group and the recurrent CRSwNP group.
Figure 6
Figure 6
The ALCAM protein expression in the tissue based on IHC. Representative images of ALCAM staining from HCs (A and B), eCRSwNP patients (C and D) and neCRSwNP patients (E and F).
Figure 7
Figure 7
The ALCAM protein expression in the nasal polyps tissue based on IHC. Representative images of ALCAM staining from non-recurrent CRSwNP patients (A and B) and recurrent CRSwNP patients (C and D).
Figure 8
Figure 8
Quantitative analysis of ALCAM immunoreactivity in nasal poly and HC samples. (A) ALCAM positive cell number was significantly greater in the eCRSwNP group than the neCRSwNP and HC groups. (B) ALCAM positive cell number was significantly greater in the recurrent CRSwNP group than the non-recurrent CRSwNP group and.
Figure 9
Figure 9
The ALCAM protein expression in the tissue based on WB. (A) WB images of ALCAM among eCRSwNP, neCRSwNP and HC groups. (B) WB images of ALCAM between the recurrent CRSwNP and non-recurrent CRSwNP groups. (C) comparison of ALCAM relative protein level among eCRSwNP, neCRSwNP and HC groups. (D) comparison of ALCAM relative protein level between the recurrent CRSwNP and non-recurrent CRSwNP groups.
Figure 10
Figure 10
Hypothetical model showing association between ALCAM expression and eosinophil infiltration and recurrence in CRSwNP. On allergens derived from irritants and bacteria challenge, DCs were activated and the production of ALCAM was increased, releasing its soluble form (sALCAM). This promoted the ALCAM–CD6 interactions and enhanced Th2 immune responses, then induced the eosinophil tissue infiltration and aggravation of eosinophilic inflammation, resulting in tissue eosinophilia and recurrence in CRSwNP.
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References

    1. Bachert C, Marple B, Schlosser RJ, et al. Adult chronic rhinosinusitis. Nat Rev Dis Primers. 2020;6(1):86. doi:10.1038/s41572-020-00218-1 - DOI - PubMed
    1. Xu X, Reitsma S, Wang Y, Fokkens WJ. Highlights in the advances of chronic rhinosinusitis. Allergy. 2021;76(11):3349–3358. doi:10.1111/all.14892 - DOI - PubMed
    1. Hopkins C. Chronic rhinosinusitis with nasal polyps. N Engl J Med. 2019;381(1):55–63. doi:10.1056/NEJMcp1800215 - DOI - PubMed
    1. Kariyawasam HH. Chronic rhinosinusitis with nasal polyps: insights into mechanisms of disease from emerging biological therapies. Expert Rev Clin Immunol. 2019;15(1):59–71. doi:10.1080/1744666X.2019.1541738 - DOI - PubMed
    1. Cho SH, Hamilos DL, Han DH, Laidlaw TM. Phenotypes of chronic rhinosinusitis. J Allergy Clin Immunol Pract. 2020;8(5):1505–1511. doi:10.1016/j.jaip.2019.12.021 - DOI - PMC - PubMed