Prognostic value of progranulin in patients with colorectal cancer underwent curative resection.

Abstract

696 Background: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the tumorigenesis and proliferation of several cancer cell types. Evidence has emerged for a potential role of PGRN as biomarkers in some diseases, however, little is known about the prognostic role of PGRN in colorectal cancers (CRCs). Methods: A retrospective analysis was performed on patients with CRCs underwent curative resection between May 2013 and June 2015. PGRN expression in tumor cells was semiquantitatively categorized (no expression, 0; weak/focal, 1+; moderate/focal or diffuse, 2+; strong/diffuse, 3+). PGRN was considered positive when either tumor cells were shown with 2+ or 3+ staining intensity. Results: A total of 109 patients (28 stage I, 32 stage II, and 49 stage III) were analyzed. The median age was 67 years (range, 30–86) and 66 patients (61%) were male. Thirty-eight patients (35%) had high tumor PGRN expression (PGRN-positive), and there was a trend of elevated pre-operative CEA and CA19–9 in patients with PGRN–positive tumor compared to those with PGRN–negative tumor (CEA, 49% vs. 21%, P = 0.003; CA19–9, 21% vs. 7%; P = 0.077). The median follow-up duration for surviving patients was 28.9 months (interquartile range, 22.5–33.9). The 3–year RFS and OS were 83.7% (95% CI, 76.8–90.6) and 96.0% (95% CI, 92.3–99.7), respectively. Patients with PGRN–positive tumors had a worse recurrence free survival (RFS) with a 66.8% at 3–year (95% CI, 51.8–81.8) compared to PGRN–negative patients with a 92.4% at 3–year (95% CI, 86.2–98.6; P = 0.01). Multivariate analysis for RFS showed that PGRN–positive tumors (hazard ratio [HR] 4.61, 95% CI, 1.26–16.93; P = 0.021) and age ( > 66 years, HR 8.87, 95% CI, 1.94–40.53; P = 0.005), stage (III, HR 8.56, 95% CI, 2.02–36.27; P = 0.004) and perineural invasion (HR 4.64, 95% CI, 1.05–20.62; P = 0.043) were prognostic factors independently associated with poor RFS after adjusting for possible confounding factors including sex, MSI status, tumor location, KRAS status, and lympho-vascular invasion. Conclusions: PGRN overexpression was significantly associated with poor RFS in patients with CRCs underwent curative resection.