High serum CCL20 is associated with tumor progression in penile cancer

Abstract

Serum cancer biomarker has been proven to be very valuable in cancer diagnosis, disease monitoring and prognosis assessment, despite there is still a lack of serum biomarker for penile cancer (PC). Our initial analysis on public GEO dataset identified CCL20 as a top C-C motif ligand (CCL) gene enriched in PC. The patients with PC exhibited markedly higher preoperative serum CCL20 level than healthy control. The area under the curve (AUC) was 0.855 with the sensitivity of 72.4%, and specificity of 93.5% to distinguish PC. Preoperative serum CCL20 level was significantly associated with clinicopathological characteristics including T stage ( P =0.005), nodal status ( P =0.008), and pelvic lymph node metastasis ( P =0.007). PC Patients with high serum CCL20 level had shorter disease-free survival compared to those with low level ( P <0.001). Cox regression analysis showed that serum CCL20 level could serve as an independent prognostic factor for disease-free survival with a HR of 3.980 (95% CI: 1.209-13.098, P =0.023). Furthermore, CCL20 expression was observed in PC tissues and cell lines. Knockdown of CCL20 expression markedly suppressed malignant phenotypes (cell proliferation, clonogenesis, apoptosis escape, migration and invasion), attenuated STAT3 and AKT signaling and reduced MMP2/9 secretion in PC cell lines. Consistently, CCL20 and its receptor CCR6 exhibited correlated expression pattern in PC tissues. In conclusion, serum CCL20 level might serve as a potential diagnostic and prognostic cancer biomarker for PC. CCL20 might activate multiple downstream oncogenic signaling pathways (STAT3, AKT, MMP2/9) to promote malignant progression of PC, which may warrant further investigation in the future.

Establishment of a Prognostic Model of Lung Adenocarcinoma Based on Tumor Heterogeneity

“…In addition, the key role of CCL20 in LUAD was identified in this study. CCL20, also called liver and activation-regulated chemokine, macrophage inflammatory protein 3 alpha, and small-inducible cytokine A20, is highly expressed in many types of cancer, including NSCLC, ovarian cancer, colorectal cancer, penile cancer, breast cancer, gastric cancer, and pancreatic cancer ( Han et al, 2015 ; Liu et al, 2016 ; Lee et al, 2017 ; Wang et al, 2019b ; Liu et al, 2020a ; Mo et al, 2020 ). This ligand has been found to enhance the migration and proliferation of cancer cells through the CCL20/CCR6 signaling pathway and to inhibit cell apoptosis, which directly promotes cancer progression.…”

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 [ 11 , 21 ]. Other serum biomarkers, such as CXCL5, CXCL13, and CCL20, are associated with nodal metastasis in small cohorts [ 32 – 34 ]. The mechanisms underlying tumor metastasis are uncertain and have become an imminent issue.…”

PD-L1 is associated with the prognosis of penile cancer: A systematic review and meta-analysis

“…Marchi et al utilized data from a public database identifying STAT1, which is potentially associated with dysfunction of the immune system, as prognostic factor for penile cancer (38). Later, it was found that the knockdown of CCL20, CXCL13, or CXCL5 gave the same results shown by significant suppression of STAT1 level and inhibition of MMP2 and MMP9 expression, leading to the diminished proliferation, migration, and invasion of penile cancer cells (39,40). SHCBP1 is a gene that has physiological associations with T cell proliferation and signaling.…”