e15607 Background: Colorectal cancer is one of the most common malignancies worldwide. Approximately 85% of colorectal cancers are thought to result from adenoma. However, the molecular mechanism of adenoma transformation into colorectal cancer is still unclear. Methods: Ninety-nine adenoma patients aged from 25 to 78 years old were enrolled in this study. We collected tissue sample from each patient and 77 matched blood samples. Pathological subtypes included tubular villous adenomas, villous adenomas, tubular adenomas, high-grade intraepithelial neoplasia, and polyps. Eighty-one stage I colorectal cancer patients (CRC I) were also enrolled in this study. All samples underwent Next-generation sequencing with a panel of 405 cancer related genes. Results: Mutational profiles of adenoma and CRC I patients were compared. The top 5 most frequently mutated genes in adenoma were APC (71%), KRAS (41%), ATM (33%), RIF1 (31%), SYNE1 (28%). While in CRC I patients, top 5 mutated genes were APC (78%), TP53 (57%), TTN (35%), KRAS (33%) and TCF7L2 (22%). There were significant differences between TP53 and TTN by chi-square test. The frequency, number and TMB of mutations in stage I colorectal cancer patients were significantly higher than those in various adenoma subtypes. Stage I colorectal cancer patients have more mutated genes enriched in the Wnt and Notch pathways than adenoma patients. We analyzed mutation signatures in CRC I and adenoma patients, and CRC I were more focused on mutation signatures of mismatch repair such as signature 1, signature 6, signature 10, and signature 15. A total of 391 mutations were identified in tissue samples, while 130 mutations were found in plasma cell-free DNA, with 116 mutations shared between them. The two genes with the highest consistency between tissue and blood were PAX7 and KMT2D. Conclusions: TP53 and TTN are associated with the transition from CRC I to adenoma, and Wnt and Notch pathways may also be involved. PAX7 and KMT2D mutations frequently found in adenoma tissue and blood cfDNA demonstrate the diagnostic potential of these two genes in clinic.
e19036 Background: The TNM classification system is the global standard for staging solid tumors, but the ability of TNM to differentiate prognostic groups may vary between settings because of differences in case-mix and treatments. Little information is available about prognostication using TNM in safety-net health systems, which provide care for socioeconomically disadvantaged individuals and have limited resources. Therefore, we aimed to assess the ability of TNM to differentiate prognostic groups for colorectal cancer patients in an urban safety-net cancer center. Methods: We used institutional registry data from the JPS Oncology and Infusion Center (Fort Worth, TX), which is a Comprehensive Community Cancer Program. Our eligible population included adults who were diagnosed with first primary colorectal cancer between 2008 and 2017, had TNM pathologic stage I – IV, and received at least part of the first course treatment at JPS. Our outcome of interest was 5-year all-cause mortality and our exposure of interest was TNM pathologic stage. Patients were followed from cancer diagnosis until death, loss to follow up, or end of study (December 31, 2018), whichever occurred first. We used a pseudo-observation approach and generalized linear models with log link to estimate risk ratios (RR) and corresponding 95% confidence limits (CL) comparing 5-year mortality between TNM stages, where stage I was the reference category. Results: Our eligible population comprised 655 colorectal cancer survivors, of whom 85% were aged < 65 years, 54% were male, 60% were racial/ethnic minorities, and 65% were uninsured at time of diagnosis. Stage IV patients had 4.4 times higher risk of 5-year mortality compared with stage I (RR = 4.4, 95% CL: 2.9, 6.6). Stage III patients had 2.1 times higher risk of 5-year mortality compared with stage I (RR = 2.1, 95% CL: 1.3, 3.2). Stage II patients had 1.4 times higher risk of 5-year mortality compared with stage I (RR = 1.4, 95% CL: 0.81, 2.3). Conclusions: Our findings suggest that TNM stages do not adequately differentiate colorectal cancer prognostic groups in a socioeconomically disadvantaged population. Stage IV is distinct, but stages I – III have limited differentiation and notable overlap. The use of TNM stages for colorectal cancer prognostication may be misleading for socioeconomically disadvantaged individuals. Factors beyond TNM should be considered for better prognostication in this population.