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. 2024 Jul 9:11:1372195.
doi: 10.3389/fmed.2024.1372195. eCollection 2024.

Prognostic and predictive role of YKL-40 in anal squamous cell carcinoma: a serological and tissue-based analysis in a multicentric cohort

Alessandro Gambella  1 , Rebecca Senetta  2 , Enrico Costantino Falco  3 , Alessia Andrea Ricci  1 , Luca Mangherini  1 , Cristian Tampieri  1 , Jessica Fissore  3 , Giulia Orlando  2 , Tilde Manetta  4 , Giulio Mengozzi  4 , Massimiliano Mistrangelo  5 , Luca Bertero  1 , Paola Cassoni  1
Affiliations

Prognostic and predictive role of YKL-40 in anal squamous cell carcinoma: a serological and tissue-based analysis in a multicentric cohort

Alessandro Gambella et al. Front Med (Lausanne). .

Abstract

Introduction: Anal squamous cell carcinoma (ASC) is a rare gastrointestinal malignancy showing an increased incidence over the past decades. YKL-40 is an immune modulator and pro-angiogenetic factor that showed a promising prognostic and predictive potential in several malignancies, but limited data are available for ASC. This study aims to provide an extensive evaluation of the prognostic and predictive role of YKL-40 in a multicenter cohort of ASC patients.

Methods: We retrospectively retrieved 72 consecutive cases of ASC diagnosed between February 2011 and March 2021. Both serum and tissue protein expression of YKL-40 were assessed, the latter in ASC tumor cells and peritumor immune cells.

Results: Increased YKL-40 serum levels at the time of diagnosis were associated with older age (p = 0.035), presence of cardiovascular/metabolic comorbidities (p = 0.007), and death for any cause (p = 0.011). In addition, high serum levels of YKL-40 were associated with a poor prognosis (HR: 2.82, 95% CI: 1.01-7.84; p = 0.047). Protein expression of YKL-40 in ASC tumor cells was significantly associated with low tumor grade (p = 0.031), while the increased expression in peritumor immune cells was associated with a worse response of patients to chemoradiotherapy (p = 0.007). However, YKL-40 protein expression in ASC tumor cells or peritumor immune cells did not significantly impact patient overall survival.

Discussion: In conclusion, YKL-40 resulted a relevant prognostic (serum level) and predictive (tissue protein expression in peritumor immune cells) biomarker and can considerably improve ASC patient clinical management.

Keywords: YKL-40; immunohistochemistry; nigro protocol; overall survival; radiochemotherapy; response to treatment; serum biomarkers.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Representative images of YKL-40 protein expression stain. (A) Score 0 in tumor cell and IC-YKLLOW. (B) Score 0 in tumor cell and IC-YKLHIGH. (C,D) Score 3 in tumor cell and IC-YKLLOW at low- (C) and high-power (D).
Figure 2
Figure 2
Kaplan-Meyer curve showing the impact of YKL-40 serological levels on patient overall survival.
See this image and copyright information in PMC

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