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.
Highlights
Gastric cancer (GC) is the fourth most common malignancy and the second leading cause of cancer deaths in the world [1]
Disease-free survival (DFS) was significantly shorter in gastric cancer (GC) patients with high urinary level of KLK10 (uKLK10) compared to those with low uKLK10
GC patients with high expression of pathological KLK10 showed a significantly shorter DFS compared to those with low pKLK10. uKLK10 is a promising non-invasive biomarker for the inoperability and incurability of GC
Summary
Gastric cancer (GC) is the fourth most common malignancy and the second leading cause of cancer deaths in the world [1]. Contrast-enhanced computed tomography (CECT) has generally been used as a diagnostic tool for staging GC for operability. CECT can detect metastasis in the lymph nodes and in distant organs such as the liver and lungs, with tumor size and enhanced intratumor intensity. It is difficult to diagnose metastasis when the metastatic tumor size is small [2]. It has been reported that CECT sensitivity, specificity, and accuracy for lymph node metastasis (LNM) detection were 25-51%, 7992%, and 64-72%, respectively [3, 4]. Difficulty with the preoperative diagnosis of peritoneal metastasis is a considerable problem for GC treatment. CECT may provide good accuracy for detecting liver metastasis, but does not have satisfactory diagnostic power for detecting pancreatic invasion, LNM, or peritoneal metastasis. CECT could not correctly diagnose GC in 45% of stage IV patients [5]
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