P3628 - Increased Methylation Level and Reduced Expression of SMOC1 Is Associated With Progression of Colorectal Traditional Serrated Adenomas

Hironori Aoki, MD, PhD¹, Akira Takasawa, MD, PhD², Eiichiro Yamamoto, MD, PhD¹, Hiro-o Yamano, MD, PhD¹, Tamotsu Sugai, MD, PhD³, Hiromu Suzuki, MD, PhD^1
1Sapporo Medical University, Sapporo, Hokkaido, Japan; ²Asahikawa Medical University, Asahikawa, Hokkaido, Japan; ³Iwate Medical University, Morioka, Iwate, Japan

Introduction: Colorectal serrated lesions (SLs) include hyperplastic polyp (HP), traditional serrated adenoma (TSA) and sessile serrated lesion (SSL). Aberrant DNA methylation is prevalent in colorectal SLs. We previously reported that SMOC1 (SPARC-related molecular calcium-binding 1) was frequently methylated and silenced in TSAs as well as in high-grade adenomas and colorectal cancers but was rarely methylated and silenced in SSLs. [1] However, the correlation between methylation and expression of SMOC1 in SLs, has not yet been studied in detail. To evaluate the potential of SMOC1 as a biomarker for diagnosis of SLs, we aimed to characterize the correlation between methylation and expression of SMOC1 in SLs.

Methods: Both methylation and expression of SMOC1 was analyzed in a series of 42 SLs and adjacent normal colonic mucosa. Methylation analysis was performed by bisulfite pyrosequencing and expression analysis was performed by immunohistochemistry (IHC). In IHC analysis, the intensity of SMOC1 staining was graded as strong (3), moderate (2), weak (1) or negative (0). The proportions of positively stained tumor cells were assigned a value of 0 to 10. Because neoplasm heterogeneity caused varying degrees of immunoreactivity in the slides, we used the sum of each intensity × proportion as an IHC score (e.g., intensity × proportion = (3) × 5 + (2) × 3 + (1) × 1 + (0) × 1 = IHC score 22; maximum score = 30) to improve accuracy.

Results: Mean methylation level (percent) in SLs and normal colonic tissues was as follows: normal colon, 5.7; HP, 2.9; SSL, 9.5; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 9.4; TSA, 36.5; TSA with high grade dysplasia (HGD)/EIC, 56.1. Mean IHC scores were as follows: normal colon, 26.5; HP, 22.7; SSL, 25.4; SSLD/SSL with EIC, 13.0; TSA, 5.2; TSA with HGD/EIC, 6.5. These results suggest that SMOC1 is frequently methylated in TSAs and TSAs with HGD/EIC but was rarely methylated in normal colon, HPs, SSLs and SSLDs/SSLs with EIC (p < 0.05), and that SMOC1 is abundantly expressed in normal colon, HPs, SSLs, whereas it is significantly downregulated in TSAs and TSAs with HGD/EIC (p < 0.05).

Discussion: We confirmed the correlation between methylation and expression of SMOC1 in SLs. Our results suggest that increased methylation level and reduced expression of SMOC1 is associated with progression of TSAs and that SMOC1 may be a biomarker for diagnosis and risk prediction of SLs.

Reference

[1] Aoki H, Yamamoto E, Takasawa A et al. Oncotarget. 2017, 4707-4721


Disclosures:


Hironori Aoki, MD, PhD¹, Akira Takasawa, MD, PhD², Eiichiro Yamamoto, MD, PhD¹, Hiro-o Yamano, MD, PhD¹, Tamotsu Sugai, MD, PhD³, Hiromu Suzuki, MD, PhD¹. P3628 - Increased Methylation Level and Reduced Expression of SMOC1 Is Associated With Progression of Colorectal Traditional Serrated Adenomas, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.