Serum CCL20 combined with IL-17A as early diagnostic and prognostic biomarkers for human colorectal cancer

Abstract

Background Noninvasive and effective methods of early diagnosis of colorectal cancer (CRC) are underexplored. Inflammation is known to play an important role in the tumor microenvironment of CRC. Therefore, the aim of this study was to elucidate novel inflammatory biomarkers related to early diagnosis and prognosis of CRC. Methods Based on the results from a multiplex assay and a pan-cancer screening of TCGA data with 18 cancer types, we identified several targeted biomarkers. We further confirmed these results using a trial cohort of 112 CRC patients and 151 controls (59 healthy donors, 52 colitis and 40 colorectal adenoma patients) by Elisa and immunohistochemistry (IHC). The biomarkers expression levels in CRC patients of different clinical stages were compared. The targeted biomarkers panel was developed using logistic regression model and was then validated using an independent cohort including 75 CRC patients and 90 controls (35 healthy donors, 20 colitis and 35 colorectal adenoma patients). Diagnostic accuracy was evaluated using area under the receiver-operating characteristic (ROC) curve and overall survival analysis was used for prognosis. Gene ontology (GO) analyses and Gene set enrichment analyses (GSEA) were performed to predict the function of the candidate biomarkers. Results CCL20 and IL-17A were identified as candidate biomarkers using multiplex assay and pan-cancer screening of TCGA data. Elisa and IHC demonstrated that both CCL20 and IL-17A levels were highly expressed in CRC patients, more especially in patients with advanced stage disease. A signature expression of the two biomarkers showed high diagnostic accuracy of CRC. Importantly, the diagnostic sensitivity and specificity were still satisfactory in the early stage and low carcinoembryonic antigen (CEA) level groups. Bioinformatics analysis revealed that CCL20 and IL-17A may be involved in CRC progression. In addition, the diagnostic performance of CCL20 and IL-17A in combination was superior to that of either marker alone. Conclusions Serum CCL20 and IL-17A levels were identified as independent prognostic markers for CRC. The CCL20-IL-17A panel exhibited a good performance in the diagnosis of early stage CRC. Electronic supplementary material The online version of this article (10.1186/s12967-019-2008-y) contains supplementary material, which is available to authorized users.

Qualitative and quantitative differences in endometrial inflammatory gene expression precede the development of bovine uterine disease

“…This chemokine has a number of functions potentially relevant to bovine reproduction including in the coordination of signals between the ovary and the uterus as well as the chemotactic response to sperm 36 . Circulating levels in serum are attracting recent interest in human studies 37 , and its significantly elevation in response to post partum disease warrants further investigation. Interestingly however, the vast majority of DEG in this comparison were decreased in cows which subsequently developed PVD relative to cows which remained healthy.…”

The CCL20-CCR6 Axis in Cancer Progression

“…Early diagnosis of CRC, which is common among both men and women [ 60 ], is important for improving prognosis, with CCL20 being a candidate biomarker. Accordingly, studies have shown that patients with CRC have significantly higher serum CCL20 and interkeukin-17 A (IL17A) levels than healthy individuals, and that receiver operating characteristic curve analysis combining CCL20 and IL17A is effective in distinguishing patients with CRC from healthy individuals [ 42 ]. Recurrence and metastasis in CRC have been the main causes of death among patients, while chemoresistance has remained a major therapeutic challenge.…”

<p>Development and Validation of a Novel 8 Immune Gene Prognostic Signature Based on the Immune Expression Profile for Hepatocellular Carcinoma</p>

“…26 In addition, the gene polymorphism of IL12A was correlated with the risk and prognosis of various tumors, including lung cancer, 27 HCC, 28 cervical cancer, 29 and gastric cancer. 30 As a chemokine, CCL20 plays an important role in the progression of tumors and is closely related to the prognosis of patients with solid tumors such as colon cancer, 31 lung cancer, 32 and pancreatic cancer. 33 PRELI was originally thought to be expressed on germinal center B lymphocytes.…”