Urinary Cysteine-Rich Protein 61 and Trefoil Factor 3 as Diagnostic Biomarkers for Colorectal Cancer

Abstract

Since a fecal occult blood test for colorectal cancer (CRC) does not offer sufficient diagnostic power for CRC, novel non-invasive biomarkers are hopeful for CRC screening. We conducted the current study to discover non-invasive urinary biomarkers for diagnosing CRC. Among urine samples from 258 patients (CRC, n = 148; healthy controls, n = 110), a cohort of 176 patients composed of 88 patients with GC and 88 healthy controls was selected after age- and sex-matching using propensity score. This cohort was then randomly divided into 2 groups: 53 pairs (106 patients) in the training cohort, and 35 pairs (70 patients) in the validation cohort. No significant differences were found for baseline characteristics between the CRC and healthy control groups in both training and validation cohorts. On multivariate analysis in the training cohort, urinary levels of cysteine-rich protein 61 (uCyr61) and trefoil factor 3 (uTFF3) were identified as independent significant diagnostic markers for CRC. Moreover, uCyr61 alone and the combination of uCyr61 and uTFF3 allowed significant differentiation between healthy controls and CRC groups in the training set (uCyr61: area under the curve (AUC) = 0.745 [95% CI, 0.653–0.838]; uCyr61 + uTFF3: AUC = 0.753 [95% CI, 0.659–0.847]). In the validation cohort, uCyr61 and uTFF3 were significantly higher in the CRC group than in the healthy control group, and they also allowed significant differentiation between healthy control and CRC groups (uCyr61: AUC = 0.696 [95% CI, 0.571–0.822]; uTFF3: AUC = 0.639 [95% CI, 0.508–0.770]; uCyr61 + uTFF3: AUC = 0.720 [95% CI, 0.599–0.841]), as in the training cohort. A panel combining uCyr61 and uTFF3 offers a promising non-invasive biomarker for diagnosing CRC.

Evaluation of kininogen 1, osteopontin and α‑1‑antitrypsin in plasma, bronchoalveolar lavage fluid and urine for lung squamous cell carcinoma diagnosis

“…Moreover, KNG1 was expressed at low levels in glioma cells (21) and renal cell carcinoma tissue (22). By contrast, increased KNG1 levels have been reported in the serum of patients with hepatocellular carcinoma (23), gastric carcinoma (24) and colorectal cancer (5). IHC staining revealed KNG1 expression to be significantly higher in colorectal cancer and advanced colorectal adenoma tissues than that in normal mucosa (25).…”

“…Such biomarkers have been sought as a means of facilitating LUSC diagnosis and monitoring, since their detection is easier than a more invasive biopsy procedure and allow rapid screening. Minimally invasive tumor biomarkers that are readily accessible in biofluids such as plasma, urine and bronchoalveolar lavage fluid (BALF) would thus offer a means of easily and effectively differentiating between patients with cancer and those with benign disease (4)(5)(6). Urine markers can be detected without exposing individuals to any risk, and urine is highly amenable to large-scale screening efforts.…”

“…However, the current biomarkers for the diagnosis of LUSC are mainly blood tumor markers such as squamous cell carcinoma (SCC) antigen and cytokeratin 19 fragment 21-1, but their sensitivity and specificity are low. There arw few studies on biomarkers of LUSC in easily accessible specimens, such as urine and BALF (4,5).…”

Urinary microRNA Biomarkers for Detecting the Presence of Esophageal Cancer

“…MicroRNA (miRNA), which is a class of small noncoding RNAs comprising approximately [18][19][20][21][22][23][24][25] nucleotides, can regulate gene expression by binding to the 3′-UTR of target mRNAs post-transcriptionally, leading to translational inhibition, or promotion of RNA degradation (7). Dysregulation of miRNAs is reportedly involved in EC tumorigenesis and progression (8)(9)(10)(11).…”

“…However, no urinary biomarkers have been clinically applied to malignant cases. We have been exploring for urinary biomarkers for a long time and found that urinary protein biomarkers are useful for gastric cancer (15)(16)(17) and colorectal cancer (18). Moreover, we recently established a urinary miRNA biomarker panel using miR-6807-5p and miR-6856-5p; this panel can early detect gastric cancer (19).…”