Urinary kallikrein 10 predicts the incurability of gastric cancer

Abstract

The current imaging modalities are not sufficient to identify inoperable tumor factors, including distant metastasis and local invasion. Hence, we conducted this study using urine samples to discover non-invasive biomarkers for the incurability of gastric cancer (GC). Urine samples from 111 GC patients were analyzed in this study. The GC cohort was categorized and analyzed according to disease stage and operability. In the discovery phase, protease protein array analysis identified 3 potential candidate proteins that were elevated in the urine of advanced GC patients compared to early GC patients. Among them, urinary kallikrein 10 (KLK10) was positively associated with tumor stage progression. Moreover, the urinary level of KLK10 (uKLK10) was significantly elevated in the urine of patients with inoperable GC compared to operable GC patients (median, 118 vs. 229; P=0.014). The combination of uKLK10, tumor location and tumor size distinguished operability of GC with an area under the curve of 0.859, 82.4% sensitivity and 86.2% specificity. Disease-free survival (DFS) was significantly shorter in GC patients with high uKLK10 compared to those with low uKLK10 (hazard ratio: 3.30 [95% confidence interval, 1.58-6.90] P<0.001). Immunohistochemical analyses also demonstrated a positive correlation between tumor stage and KLK10 expression in GC tissues (r=0.426, P<0.001). In addition, GC patients with high expression of pathological KLK10 (pKLK10) showed a significantly shorter DFS compared to those with low pKLK10 (hazard ratio: 3.79 [95% confidence interval, 1.27-11.24] P=0.010). uKLK10 is a promising non-invasive biomarker for the inoperability and incurability of GC.

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

“…Urine sampling is a straightforward and non-invasive procedure with low risks and costs, representing an attractive option for biomarker detection. We have previously shown the utility of urinary biomarkers for the early detection 10 and prediction of curability 11 against gastric cancer. Urinary biomarker is thus an attractive, non-invasive tool for the detection of malignancies.…”

“…All urine samples were collected before any treatment for CRC, immediately frozen and stored at −80 °C until assayed, as previously reported [10], [11]. Clinical stage was determined by the final pathological diagnosis after resection, according to the 7th edition of the Union for International Cancer Control tumor-node-metastasis classification 14…”

“…However, no urinary biomarkers have been currently applied to the clinical setting of malignancies. We have previously reported on the utility of urinary biomarkers to predict the presence 10 or operability 11 of gastric cancer. We therefore investigated the usefulness of urinary biomarkers for detecting CRC.…”

Urinary microRNA Biomarkers for Detecting the Presence of Esophageal Cancer

“…Urine and serum samples were collected before any treatment for EC, immediately frozen, and stored at − 80 °C until assayed, as previously reported (16)(17)(18)(19). We obtained EC tissues and matched adjacent normal tissues from patients who underwent surgery or endoscopic submucosal dissection (ESD).…”

“…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).…”