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PLASMA LEVELS OF ACTIVIN A ARE SIGNIFICANTLY ELEVATED IN PATIENTS WITH LARGE ADENOMAS TO PATIENTS WITH NON-NEOPLASTIC BENIGN COLORECTAL CONDITIONS
Hmc Shantha Kumara
*1, Hiromichi Miyagaki
2, Yi-Ru Chen
1, Neil Mitra
1, Elizabeth Nilsson Sjolander
1, Xiaohong Yan
3, Vesna Cekic
1, Richard L. Whelan
11Department of Surgery, Lenox Hill Hospital, Northwell Health, New York, NY; 2Department of Surgery, Otemae Hospital, Chuo-ku,, Osaka, Japan; 3Department of Pathology and Cell Biology, Columbia University Medical Center, Vanderbilt Clinic, New York, NY
Introduction: Activin A(ActA) is in the TGF-? cytokine family and is a homodimer of two ?A subunits. After binding to the transmembrane serine/threonine kinase receptors (ActRIIA or ActRIBI) ActA activates the SMAD signaling pathway, which regulates the transcription of ActA response genes. The expression of ActA is heterogeneous among various tissues and cell types, playing a vital role in the regulation of numerous physiological processes including cell growth, apoptosis, wound healing, inflammation, and immune responses. ActA is a vital mediator of VEGF induced angiogenesis and is also involved in capillary formation stimulated by FGF-2. ActA is overexpressed in various malignancies, including colorectal cancer. ActA expression has been correlated with increased tumor cell proliferation, invasion and poor patient prognosis. We have reported significant elevation of plasma ActA levels in colorectal cancer (CRC) patients (pts.) compared to levels in patients (pts) with benign colorectal disease. This study compares ActA plasma levels in surgical patients with large benign adenomas (+/- high grade dysplasia (HGD) to patients with non-neoplastic BCD (NN-BCD; diverticulitis, rectal prolapse, etc.,).
Methods: Pts undergoing elective surgeries for large adenomas or NN-BCD were prospectively enrolled in an IRB approved tissue and data bank. Basic demographic, clinical data and pathology results were prospectively collected. Blood samples were collected and processed; plasma was stored at -80
0C until utilized. Plasma ActA levels was determined in duplicate via ELISA, and results reported as median and 95% CI. The Mann-Whitney test was used to compare ActA levels between the different groups (sig. p<0.05).
Results: Preoperative (Preop) plasma from 142 patients was assessed; 60 adenoma pts (52 pts [87%]; HGD, 8 pts, [13%]) and 82 NN-BCD pts (93% diverticulitis, 7% other). [The polyp locations were: right, 66%; transverse, 6%; left/sigmoid, 14%; and rectal, 14%.] The mean male to female ratios in the groups were comparable. The mean ActA level was significantly higher in the Adenoma group than the NN-BCD group (283.2 95% CI 226.9, 363.6 pg/ml vs 226.6 95% CI 204.7, 271.3 pg/ml, p=0.038). A non-significant elevation (41% higher) in Act A levels were noted in the HGD subgroup vs the non-dysplastic adenoma group pts.
Conclusion: Preop plasma ActA levels were significantly elevated in adenoma pts (median, 25% higher) compared to NN-BCD pts. Also, the median plasma ActA level in HGD pts was 41% higher than that of the adenoma pts. Elevated ActA levels observed in patients with adenomas may be linked to inflammation associated with neoplastic polyp progression. To better assess the relationship between ActA levels and the differentiation of polyps, more research involving a larger cohort of both cancer-free controls and adenoma and HGD patients is needed.
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