Abstract 3138: Colorectal cancer is associated with elevated plasma levels of soluble platelet-derived growth factor-dd (PDGF-DD) compared to plasma levels of benign colon disease patients

Abstract

Abstract Introduction: Platelet-derived growth factor-DD (PDGF-DD), a member of the PDGF family, is secreted as a latent homodimer which is activated by uPA (urokinase). After binding to its receptor, PDGF Rβ, PDGF-DD plays a role in mesenchymal transition, cancer cell growth, migration, and invasion all of which are supported by the PDGF DD induced proangiogenic proteins MMP2, MMP9 and VEGF. Downregulation of PDGF DD suppresses both the expression of VEGF and MMP9 via Notch-1, NF-kappaB and VEGF directed neo-angiogenesis. Upregulated expression of PDGF DD has been noted in colon and many other cancers. This study's purpose was to compare preoperative (PreOp) plasma PDGF DD levels in colorectal cancer (CRC) and benign colon disease (BCD) patients (pts). Method: Pts undergoing colorectal resection for CRC or benign problems that had been prospectively enrolled in an IRB approved tissue and data bank for whom adequate Preop plasma samples were available were studied. Clinical, demographic, operative, and pathologic data were collected. The PDGF-DD levels in the preoperative plasma samples were determined via ELISA in duplicate and reported as median ±95% CI (pg/ml). The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the CRC diagnostic value of plasma protein levels. The Mann-Whitney test was used for statistical analysis, (significance (sig) p<0.05). Results: A total of 116 CRC (72% colon, 28% rectal) and 86 benign disease pts (adenoma 31%, diverticulitis 55 %, other 14%) were studied. The male: female ratios were similar but the CRC pts were older (p=0.001). The CRC stage distribution was: stage 1, 33 (28%); stage 2, 33 (28%); stage 3, 41 (36%); stage 4, 9 (8%). The median PreOp plasma PDGF DD level was significantly higher in the CRC group (386.8, CI: 341.2, 498.8) than in the benign disease group (320.4, CI: 281.414.5, p<0.001). No correlation was found between PDGF-DD levels and tumor stage. In sub group analysis, tumor expression of PDGF-DD was confirmed by IHC in 8/10 pts (tumor vs. paired normal tissue). The AUC for the ROC curve (AUC) for plasma PDGF DD in association with a diagnosis of CRC was 0.62751 (sensitivity 29%, specificity 95%). Conclusion: Preoperative plasma PDGF-DD levels were evaluated in CRC pts and compared to those in benign colorectal disease pts. The median plasma PDGF-DD level in CRC pts was 21% higher than the median level in BCD pts. AUC value suggests that PDGF-DD may be a potential candidate for a prognostic marker panel for CRC. The higher levels in CRC pts could be attributed to tumor-related inflammation, progression, and angiogenesis. Further studies with a larger population of cancer free control and CRC pts are necessary to better determine whether PDGF-DD levels correlate with Cancer stage and prognosis. Citation Format: Chandana S K Herath Mudiyanselage, Neil Mitra, Dasuni Niyagama Gamage, Hiromichi Miyagaki, Abhinit Shah, Xiaohong Yan, Vesna Cekic, Richard L. Whelan. Colorectal cancer is associated with elevated plasma levels of soluble platelet-derived growth factor-dd (PDGF-DD) compared to plasma levels of benign colon disease patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3138.