Use of liquid biopsy molecular profiling among Native American patients with pancreatic ductal adenocarcinoma: A retrospective study from a minority-serving cancer center (2017-2022).

Abstract

777 Background: Pancreatic ductal adenocarcinoma (PDAC) molecular profiling guides treatment selection, yet liquid biopsy reliability and minority population data remain limited. In New Mexico, PDAC incidence varies by ethnicity (Hispanic: 15.0/100,000; Native American: 8.5/100,000), but molecular drivers are unknown. We evaluated mutation detection by biopsy type and molecular patterns across ethnic groups at University of New Mexico Comprehensive Cancer Center. Methods: Retrospective analysis of 74 PDAC patients (2017-2022) undergoing next-generation sequencing. Three patients were excluded from biopsy comparison (two with mixed blood/tissue samples, one unknown), leaving 71 patients: tissue (n=54) or liquid biopsy (n=17). Of 74 participants, race was White in 78% (58), American Indian/Alaska Native in 11% (8), Asian in 5% (4), Black/African American in 1% (1), and other/unknown in 4% (3). Ethnicity was Hispanic/Latino in 28% (21). Fisher's exact test compared mutation frequencies. Results: Liquid biopsy significantly underdetected mutations compared to tissue biopsy: KRAS 47% vs 93% (p=0.0001), TP53 47% vs 85% (p=0.001), SMAD4 0% vs 33% (p=0.004), CDKN2A 18% vs 56% (p=0.010). Native American patients (n=8) demonstrated distinct molecular patterns compared to White patients (n=58): significantly lower TP53 mutations (38% vs 79%, p=0.023), absence of SMAD4 mutations (0% vs 29%, p=0.101), and reduced KRAS prevalence (63% vs 85%, p=0.152). Hispanic patients showed a trend toward higher KRAS G12D frequency compared to G12V/G12R combined (45% vs 23%, p=0.10). Conclusions: Liquid biopsy failed to detect critical PDAC mutations, limiting the ability to perform comprehensive molecular profiling, particularly given that tissue confirmation remains necessary for clinical trials and optimal treatment selection. Native Americans showed distinct profiles with lower TP53 mutations, suggesting different tumor biology. These findings emphasize tissue profiling importance and need for expanded studies in underrepresented populations to optimize precision medicine approaches. Mutation detection by biopsy type and race in PDAC patients. Characteristic n/N (%) p-value Liquid vs Tissue Biopsy  KRAS: Liquid / Tissue 8/17 (47%) / 50/54 (93%) 0.0001  TP53: Liquid / Tissue 8/17 (47%) / 46/54 (85%) 0.001  SMAD4: Liquid / Tissue 0/17 (0%) / 18/54 (33%) 0.004  CDKN2A: Liquid / Tissue 3/17 (18%) / 30/54 (56%) 0.010 Native American vs White  KRAS: Native / White 5/8 (63%) / 49/58 (85%) 0.152  TP53: Native / White 3/8 (38%) / 46/58 (79%) 0.023  SMAD4: Native / White 0/8 (0%) / 17/58 (29%) 0.101  CDKN2A: Native / White 2/8 (25%) / 28/58 (48%) 0.275