PREOPERATIVE PLASMA LEVELS OF PROGRANULIN AND OSTEOPONTIN IN COLORECTAL CANCER VS BENIGN DISEASE PATIENTS AND EVALUATION OF THE POTENTIAL OF THIS TWO PROTEIN COMBINATION TO DIAGNOSE COLORECTAL CANCER
Hmc Shantha Kumara*1, Hiromichi Miyagaki2, Neil Mitra1, Yanni Hedjar1, Xiaohong Yan1, Vesna Cekic1, Joseph Martz1, Jennifer L. Agnew1, Richard L. Whelan1
1Surgery, Lenox Hill Hospital, Northwell Health, New York, NY; 2Osaka Rousai Hospital, Japan, Japan
Introduction: Progranulin (PGRN) is a glycoprotein expressed by a wide variety of cells including endothelial cells. PGRN promotes cyclin D1 and cyclin B expression which supports the proliferation and survival of mesenchymal and epithelial origin cells. PGRN modulates VEGF expression in breast cancer cells in vitro and stimulates inflammation and vasculogenesis. Osteopontin (OPN), produced by activated macrophages and leukocytes, is an integrin binding phosphorylated glycoprotein involved in numerous physiopathological events including cell-mediated immunity, inflammation, tumor progression, and cell survival. OPN also impacts VEGF mediated tumor vascular invasion and tumor progression. Lastly, PGRN and OPN overexpression has been noted in many cancers including colorectal cancer (CRC). This study's aim was to determine preoperative plasma levels of PGRN and OPN in a population of CRC and benign colonic disease (BCD) patients (pts) and to assess the value of a combination of these proteins to diagnose CRC.
Methods: Preoperative (Preop) plasma samples from consenting CRC and BCD pts undergoing elective colorectal resection that were enrolled in an IRB approved tissue/data bank were eligible for this study. Demographic, clinical and pathologic data were reviewed. Plasma levels of PGRN and OPN (ng/ml) were determined in duplicate via ELISA and reported as median + 95%CI. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the CRC diagnostic value of single and combined plasma protein levels. The Mann-Whitney test was used for statistical analysis (significance p<0.05).
Results: A total of 172 CRC (70% colon, 30% rectal) and 102 BCD pts (adenoma 33%, diverticulitis 53%, other14%) were included in the study. The CRC pathologic stage (stg) breakdown was: Stg-1, 25%; Stg-2, 32%, Stg-3, 31%, Stg-4, 12%. The CRC median preop plasma protein (PGRN and OPN) levels were significantly higher vs. the BCD group median levels, respectively, [PGRN; 54.7, CI: 51.7, 57.1 vs 43.3, CI: 40.1, 46.9; OPN; 82.3, CI: 77.1, 89.3vs 63.9, CI: 54.9, 69.0; P<0.001). Plasma OPN levels in Stg-4 was higher vs Stg-1 (p=0.01). Non-significant increases in the mean plasma levels of PGRN (5-16%) and OPN (10-62%) were noted with advancing cancer stg. The AUC value for ROC curve for PGRN and OPN were 0.724 and 0.702 respectively with 71% and 78% specificity. The AUC for the combination of the 2 proteins was 0.779 with 84% specificity.
Conclusion: The median PGRN and OPN values in CRC pts were significantly higher (26% and 29%) then BCD levels. The two protein combination had improved AUC & specificity vs single protein results and may have value as a diagnostic panel. Further study with larger population of healthy control and CRC pts is warranted.
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