|
|
Back to 2018 Posters
COLORECTAL CANCER IS ASSOCIATED WITH ELAVATED PLASMA LEVELS OF PROGRANULIN
H M C Shantha Kumara*1, Carl Winkler1, Sandhu K. Jaspreet1,2, Simon Tian1, Abhinit Shah1, Xiaohong Yan1, Hiromichi Miyagaki1,3, Vesna Cekic1, Nipa D. Gandhi1, Richard L. Whelan1
1Surgery, Mount Sinai West Hospital, New York, NY; 2Surgery, Brookdale Hospital Medical Center, New York, NY; 3Surgery, Saiseikai Senri Hospital, Osaka-565-0862, 1-1-6, Tsukumodai, Suita, Japan
Introduction: Progranulin (PGRN), also known as PC cell-derived growth factor (PCDGF), is a ubiquitously expressed secreted glycoprotein. Progranulin is involved in the regulation of cellular proliferation, as well as differentiation and pathological processes. As a growth factor, PGRN activates both the PI3k and ERK pathways, and promotes the expression of cyclin D1 and cyclin B that stimulate the proliferation and survival of mesenchymal and epithelial origin cells. PGRN stimulates VEGF expression in breast cancer cells in vitro and stimulates inflammation, fibroblast accumulation and new blood vessel formation. Over-expression of PGRN has been reported in breast and ovarian cancers as well as multiple myeloma and glioblastoma, however, PGRN levels in colorectal cancer (CRC) patients (pts) has not been well studied. The aim of this study was to compare preoperative plasma PGRN levels in CRC and benign colonic disease (BCD) pts.
Methods: Pts undergoing colorectal resection for BCD or CRC were prospectively enrolled in an IRB approved tissue and data banks. Preoperative blood samples, basic demographic data, operative data, and pathology results were prospectively collected. Plasma PGRN levels were determined in duplicate (ng/ml) via ELISA, and results are reported as median ± 95% CI. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to assess plasma PGRN as a diagnostic tool for CRC. The Mann-Whitney test was used for statistical analysis, (significance, p<0.05).
Results: A total 196 CRC (75% colon, 25% rectal) and 120 BCD pts (55% diverticulitis, 24% adenoma and 21% other) were assessed. The male to female ratios were comparable, but the CRC pts were older (p<0.001). The final cancer staging in the CRC group: stage 1, 29%; stage 2, 31%; stage 3, 28%; stage 4, 12%. The median PGRN level was significantly higher in the CRC group than the benign group (54.7, CI: 52.5, 62.3 vs. 45.6, CI: 42.6,48.6, p<0.001). No significant differences in PGRN levels were noted between the different pathologic stage groups. The AUC value for ROC curve was 0.715(sensitivity 47%, specificity 68%).
Conclusion: The median Preop plasma PGRN was 20% higher in the CRC vs. the BCD group. Although not proven, the source of the added PGRN in the plasma of CRC pts may be the tumor and inflammatory cells surrounding the cancer. Elevated PGRN levels may be related to neovascularization and inflammation-induced tissue remodeling at tumor sites. The AUC results suggest PGRN may have value as a CRC prognostic marker. Further studies with a larger population of healthy control and CRC pts are needed to better determine if there is a correlation between plasma PGRN levels and cancer stage or progression.
Back to 2018 Posters
|
