<p>Serum CXCL13 Level is Associated with Tumor Progression and Unfavorable Prognosis in Penile Cancer</p>

Abstract

Background: Chemokine (C-X-C motif) ligands (CXCLs) are important regulators of tumor progression in many cancers and could serve as potential cancer biomarkers. However, the expression patterns as well as functions of CXCLs remain unclear in penile cancer (PC). The aim of this study was to evaluate the usefulness of serum CXCL13 as a potential cancer biomarker for PC. Patients and Methods: This retrospective study enrolled 76 patients diagnosed with PC between 2016 and 2018. Serum CXCL13 level was detected by enzyme-linked immunosorbent assay. Univariable and multivariable Cox regression analyses were conducted to identify the prognostic factors that influence disease-free survival. Human penile cancer cell lines Penl1, Penl2, 149RCa and LM156 were used as in vitro models. The expression of CXCL13 protein in PC cell lines was analyzed by Western blotting. Results: Our initial analysis on GSE57955 dataset identified CXCL13 as a top CXCL gene enriched in PC. Higher preoperative serum CXCL13 level was detected in PC cohorts than in healthy male controls (P<0.001). The area under the curve was 0.911 with the sensitivity of 84.2% and specificity of 87.0% to distinguish PC. Preoperative serum CXCL13 level was associated with pathological grade (P=0.048), T stage (P=0.009), nodal status (P<0.001) and pelvic lymph node metastasis (P=0.005) in PC. Serum CXCL13 level could serve as an independent prognostic factor for disease-free survival with a HR of 3.818 (95%CI: 1.126-12.946). Furthermore, autocrine expression of CXCL13 was detected in PC tissues and cell lines. Knockdown of CXCL13 expression suppressed malignant phenotypes (cell proliferation, clonogenesis, apoptosis escape, migration and invasion), attenuated STAT3 and ERK1/2 signaling and reduced MMP2/9 secretion in PC cell lines. Conclusion: Serum CXCL13 could serve as a novel diagnostic and prognostic biomarker for PC. CXCL13 signaling might activate oncogenic signaling pathways to promote malignant progression of PC.

Identification and Comprehensive Prognostic Analysis of a Novel Chemokine-Related lncRNA Signature and Immune Landscape in Gastric Cancer

“…Different types of immune cells could be recruited into the tumor microenvironment via interactions between chemokines and chemokine receptors (Nagarsheth et al, 2017). Altered expression levels of chemokines in malignant tumors are associated with angiogenesis, proliferation, metastasis and recruitment and activation of immune cells in multiple tumors (Strieter et al, 2005;Teicher and Fricker, 2010;Santoni et al, 2014;Li et al, 2017;Yang et al, 2017;Liang et al, 2018;Mo et al, 2020;Yang et al, 2020). Many anti-chemokine drugs have been used in combination with other antitumor drugs in cancer treatment (Feig et al, 2013;Salazar et al, 2018).…”

miR-138-5p-mediated HOXD11 promotes cell invasion and metastasis by activating the FN1/MMP2/MMP9 pathway and predicts poor prognosis in penile squamous cell carcinoma

“…Several studies have reported that RAB20 and IDO1 overexpression promote cell proliferation and induce immunosuppression in PSCC [12,21]. Other serum biomarkers, such as CXCL5, CXCL13 and CCL20, are associated with nodal metastasis in small cohorts [33][34][35]. The mechanisms underlying tumor metastasis are uncertain and have become an imminent issue.…”

STAT3 and Its Pathways Dysregulation – Underestimated Role in Urological Tumors

“…High preoperative serum levels of mentioned chemokines were associated with tumor progression and poor outcomes. That is why scientists suggest using CCL20, CXCL13 and CXCL5 as diagnostic and prognostic biomarkers [133][134][135].…”