MUC5AC levels as predictors of adjuvant therapy outcomes in pancreatic ductal adenocarcinoma: A study of post-surgical gemcitabine-based regimens.

Abstract

759 Background: The role of tissue mucin 5 AC (MUC5AC) in PDA is not fully understood. In our previous work we showed that mature MUC5AC (MM) detected in the extracellular (EC) space and in apical region has better prognostic value than perinuclear immature MUC5AC (IM). Our previous research demonstrated that mature MUC5AC (MM), present in the extracellular (EC) space and apical region, offers better prognostic value than perinuclear immature MUC5AC (IM). Preclinical studies suggest that MM may confer chemoresistance to gemcitabine (Gem), commonly used in adjuvant therapy (AT) either alone or with capecitabine (Cap) or nab-paclitaxel (NP) in patients not eligible for FOLFIRINOX. This study investigates MM’s effect on outcomes in PDA patients undergoing post-surgical treatment with Gem-only, Gem-NP, and Gem-Cap. Methods: Formalin-fixed, paraffin-embedded tissue samples from resected PDA cases (January 2010 - June 2021) were sourced from the Ohio State University biorepository. Immunohistochemistry using monoclonal antibodies 45M1 (for MM) and CLH2 (for IM) was employed to examine cellular MM and IM expression, with H-scores calculated. Statistical analysis of progression-free survival (PFS) and overall survival (OS) was done using the log-rank test. Results: We had 49 patients available for analysis. The median age of the group was 66 years (range: 38 to 89) with majority Caucasians (90%) and 53% (n=26) females. AT distribution within this group was, 31 Gem-only, 7 Gem-NP, and 11 Gem and capecitabine (Cap). Median expression levels for MM and IM were both 150, and 82% (n=40) were EC-MM positive. Using the median MM H-score as a threshold (< 150 vs. ≥ 150), outcomes were evaluated within each therapy subgroup (Table). Conclusions: This preliminary study suggests that PDA patients with low MM expression may benefit from Gem-Cap therapy. However, larger, prospective studies are needed for definitive conclusions. Comparing outcomes in the sub-groups. Sub-group (n) OS in days (p-value) PFS in days (p-value) MM H-score < 150 vs. ≥ 150 Gem-only (11 vs. 20) 775 vs. 1006 (0.4) 444 vs. 413 (0.4) Gem NP (4 vs. 3) 1409 vs. 551 (0.8) 391 vs. 418 (0.5) Gem-Cap (4 vs. 7) not evaluable (NE) vs. 766 (0.02) NE vs. 415 (0.01)