Prognostic Value of Progranulin in Patients with Colorectal Cancer Treated with Curative Resection.

Progranulin (PGRN) has been characterized as an autocrine growth and survival factor and is known to stimulate tumorigenesis and proliferation of several types of cancer cell. However, little is known about the prognostic role of PGRN in colorectal cancer (CRC). A retrospective analysis was performed for patients with colorectal cancer who underwent curative resection between May 2013 and June 2015. PGRN expression in tumor cells was semi-quantitatively categorized (no expression, 0; weak/focal, 1+; moderate/focal or diffuse, 2+; strong/diffuse, 3+), and high expression was considered for tumors graded ≥2+ staining intensity. A total of 109 patients (28 stage I, 32 stage II, and 49 stage III) were analyzed. Thirty-eight patients (35%) had tumors with high PGRN expression, and there was a trend of elevated pre-operative CEA and CA19-9 levels in patients with high PGRN-expressing tumors compared to those with low PGRN-expressing tumors (CEA, 49% vs. 21%; CA19-9, 21% vs. 7%). The 3-year recurrence-free survival (3Y-RFS) and overall survival rates were 83.7% (95% CI, 76.8-90.6) and 96.0% (95% CI, 92.3-99.7), respectively. Patients with high PGRN-expressing tumors had a worse rate of 3Y-RFS (66.8%) compared to those with low PGRN-expressing tumors (92.4%; p = 0.010). Multivariate analysis showed that high PGRN expression, age (>66 years), stage (III), and perineural invasion (+) were independent prognostic factors associated with poor RFS after adjusting for confounding factors including sex, MSI, tumor location, KRAS, and lympho-vascular invasion. PGRN overexpression was significantly associated with poor RFS in patients with CRC who have undergone curative resection.

Is methylation analysis of SFRP2, TFPI2, NDRG4, and BMP3 promoters suitable for colorectal cancer screening in the Korean population?

BACKGROUND/AIMS: Colorectal cancer (CRC) screening using stool DNA was recently found to yield good detection rates. A multi-target stool DNA test (Cologuard®, Exact Sciences), including methylated genes has been recently approved by the U.S. Food and Drug Administration. The aim of this study was to validate these aberrantly methylated genes as stool-based DNA markers for detecting CRC and colorectal advanced adenoma (AA) in the Korean population. METHODS: A single-center study was conducted in 36 patients with AA; 35 patients with CRC; and 40 endoscopically diagnosed healthy controls using CRC screening colonoscopy. The methylation status of the SFRP2, TFPI2, NDRG4, and BMP3 promoters was investigated blindly using bisulfate-modified stool DNA obtained from 111 participants. Methylation status was investigated by methylation-specific polymerase chain reaction. RESULTS: Methylated SFRP2, TFPI2, NDRG4, and BMP3 promoters were detected in 60.0%, 31.4%, 68.8%, and 40.0% of CRC samples and in 27.8%, 27.8%, 27.8%, and 33.3% of AA samples, respectively. The sensitivities obtained using 4 markers to detect CRC and AA were 94.3% and 72.2%, respectively. The specificity was 55.0%. CONCLUSIONS: Our results demonstrate that the SFRP2, TFPI2, NDRG4, and BMP3 promoter methylation analysis of stool sample DNA showed high sensitivity but low specificity for detecting CRC and AA. Because of the low specificity, 4 methylated markers might not be sufficient for CRC screening in the Korean population. Further large-scale studies are required to validate the methylation of these markers in the Asian population and to find new markers for the Asian population.

Prospective Analysis of Minor Adverse Events After Colon Polypectomy.

BACKGROUND: The risks of minor adverse events (MAEs) such as abdominal pain and bloating after colon polypectomy (CP) are less clearly documented than major adverse events. However, these complications may cause significant discomfort during the performance of normal activities. We aimed to estimate the incidence of MAE, associated risk factors, and healthcare resource utilization after CP. METHODS: Patients who underwent CP were prospectively enrolled in this study. Trained nurses contacted patients by telephone at 7 and 30 days after the CP and administered a standardized questionnaire to obtain information regarding the development of complications. MAEs were defined as any discomfort the patient experienced after CP excluding major bleeding, perforation, and post-polypectomy coagulation syndrome. RESULTS: Among a total of 2716 patients, 2253 patients completed the interview at 7 and 30 days. MAEs occurred in 263 patients (11.7%) before day 7, among which the most common were abdominal pain (4.5%), rectal bleeding (2.8%), and bloating (2.6%). Cumulative incidence of MAEs was in 267 patients (11.9%) at 30 days. On multivariate analysis, female sex (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.58-3.18) and use of meperidine (OR 1.54, 95% CI 1.04-2.27) were risk factors for the occurrence of MAEs. Two patients (0.7%) required hospital admission, 117 patients (43.8%) were treated medically in the outpatient clinic, and the majority at 148 patients (55.4%) experienced resolution of symptoms after observation. CONCLUSIONS: The post-CP MAE rate was as low as 11.8%. The MAEs occurred mainly in the first seven postoperative days and resulted in little use of healthcare resources.

Erratum: Field Cancerization in Sporadic Colon Cancer.

In the version of this article initially published, the first affiliation (affiliation number 1) was incorrectly stated as "Division of Gastroentorology, Department of Internal Medicine." The correct affiliation is "Department of Internal Medicine."

Field Cancerization in Sporadic Colon Cancer.

BACKGROUND/AIMS: Aberrant DNA methylation has a specific role in field cancerization. Certain molecular markers, including secreted frizzled-related protein 2 (SFRP2), tissue factor pathway inhibitor 2 (TFPI2 ), N-Myc downstream-regulated gene 4 (NDRG4) and bone morphogenic protein 3 (BMP3), have previously been shown to be hypermethylated in colorectal cancer (CRC). We aim to examine field cancerization in CRC based on the presence of aberrant DNA methylation in normal-appearing tissue from CRC patients. METHODS: We investigated promoter methylation in 34 CRC patients and five individuals with normal colonoscopy results. CRC patients were divided into three tissue groups: tumor tissue, adjacent and nonadjacent normal-appearing tissue. The methylation status (positive: methylation level >20%) of SFRP2 , TFPI2 , NDRG4 , and BMP3 promoters was investigated using methylation-specific PCR. RESULTS: The methylation frequencies of the SFRP2 , TFPI2 , NDRG4 and BMP3 promoters in tumor/adjacent/nonadjacent normal-appearing tissue were 79.4%/63.0%/70.4%, 82.4%/53.6%/60.7%, 76.5%/61.5%/69.2%, 41.2%/35.7%/50.0%, respectively. The methylation levels of the SFRP, TFPI2, NDRG4 and BMP3 promoters in tumor tissues were significantly higher than those in normal-appearing tissue (SFRP2, p=0.013; TFPI2, p<0.001; NDRG4, p=0.003; BMP3, p=0.001). No significant correlation was observed between the methylation levels of the promoters and the clinicopathological variables. CONCLUSIONS: The field effect is present in CRC and affects both the adjacent and nonadjacent normal-appearing mucosa.