A Novel Urinary miRNA Biomarker for Early Detection of Colorectal Cancer

Since noninvasive biomarkers as an alternative to invasive colonoscopy to detect colorectal cancer (CRC) are desired, we conducted this study to determine the urinary biomarker consisting of microRNAs (miRNAs). In total, 415 age- and sex-matched participants, including 206 patients with CRC and 209 healthy controls (HCs), were randomly divided into three groups: (1) the discovery cohort (CRC, n = 3; HC, n = 6); (2) the training cohort (140 pairs); and (3) the validation cohort (63 pairs). Among 11 urinary miRNAs with aberrant expressions between the two groups, miR-129-1-3p and miR-566 were significantly independent biomarkers that detect CRC. The panel consisting of two miRNAs could distinguish patients with CRC from HC participants with an area under the curve (AUC) = 0.811 in the training cohort. This panel showed good efficacy with an AUC = 0.868 in the validation cohort. This urinary biomarker combining miR-129-1-3p and miR-566 could detect even stage 0/I CRC effectively with an AUC = 0.845. Moreover, the expression levels of both miR-129-1-3p and miR-566 were significantly higher in primary tumor tissues than in adjacent normal tissue. Our established novel biomarker consisting of urinary miR-129-1-3p and miR-566 enables noninvasive and early detection of CRC

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

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

The Risk Analyses of Lymph Node Metastasis and Recurrence for Submucosal Invasive Colorectal Cancer: Novel Criteria to Skip Completion Surgery

(1) Background: Additional surgical resection after endoscopic resection (ER) is recommended for patients with submucosal invasive colorectal cancer (pT1 CRC) who have risk factors for lymph node metastasis (LNM) (high-risk pT1 CRC). This study aimed to identify risk factors for LNM and metastatic recurrence and to determine the low-risk population for whom additional surgery can be omitted among high-risk pT1 CRCs. (2) Methods: We retrospectively identified 404 patients with pT1 CRC who underwent ER or surgery, and patients were divided into three groups: low-risk (n = 79); high-risk pT1 with ER (n = 40); and high-risk with surgery (n = 285). We also enrolled another 64 patients with high-risk pT1 CRC in an independent validation cohort. (3) Results: In the high-risk with surgery group, LNM was seen in 11.2%, and vascular and lymphatic invasions were significantly independent risk factors for LNM on multivariate analysis. No LNMs were observed in pT1 CRCs with a negative vertical margin and SM invasion depth ≤2000 µm that had no other risk factors except for budding. Five patients developed metastatic recurrence in the high-risk with surgery group, and rectal cancer and undifferentiated histology were significantly independent risk factors for poor relapse-free survival. No LNM or recurrent cases were seen in high-risk pT1 CRCs that met these criteria: differentiated adenocarcinoma, no lymphovascular invasion, colon cancer, SM invasion depth ≤2000 μm, and a negative vertical margin, which were validated in an independent validation cohort. (4) Conclusions: Completion surgery may be skipped for high-risk pT1 CRCs that meet our proposed criteria

Urinary kallikrein 10 predicts the incurability of gastric cancer

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