S413 Comparative Efficacy of Antibiotic Treatments for Clostridioides difficile Infection: A Meta-Analysis of Randomized Controlled Trials

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Introduction: The colorectal carcinoma (CRC) is the most prevalent cancer, and carries a poor prognosis. Information regarding whole genome sequencing, a prognostic prediction system, and overall survival in CRC is limited. While mutation of TP53 and APC are commonly implicated in CRC, EGFR, MLH1, MSH2, MSH6, PMS2, TGFBR2, KRAS, SMAD4, PTEN, and BRAF genes have limited literature on their correlation to CRC. Hence, we aimed to analyze the genomic profile, epidemiological characteristics, and overall survival of CRC. Methods: We utilized cBioPortal cancer genomics (The Cancer Genome Atlas [TCGA] PanCancer Atlas, TCGA Firehose Legacy, and TCGA Nature 2012, and MSKCC) to study the genetic mutations associated with CRC. Epidemiological characteristics and genetic profiles were evaluated, and a query was generated to calculate the 10-year survival rate with the most common mutations. Log-rank test and Kaplan–Meier estimator were used in analyzing the survival function. Patients with 2 or more overlapping mutations (435) were excluded. Results: We identified 5,272 samples (5,062 patients) with CRC. Out of which 4,628 (87.8%) had one or more mutations. The most common mutations were APC (72.5%), TP53 (67.1%), TTN (44.8%), KRAS (42.5%), SYNE1 (25.2%), MUC16 (23.7%), FAT4 (19.8%), PIK3CA (19.7%), FLG (19.1%), LRP1B (17.0%). The most common treatment utilized for CRC was fluorouracil, leucovorin, oxaliplatin, bevacizumab, and radiation. Overall, 1,951 (37% samples) patients were between the ages of 50-80 years; 2442 (46.3%) had primary CRC, and 14.1% had metastasis; 50.7% were males, 23.3% were White, and 2.5% were African American. Median survival of patients with APC (49 months), TP53 (39 months), MLH1 (38 months), MSH6 (22 months), SMAD4 (49 months), BRAF (31 months), EPCAM (41 months), and BMPR1A (34 months) mutations was lower in comparison with the unaltered mutation group (62 months) (P < 0.0001). In survival analysis, MLH1 was associated with the lowest survival after initial diagnosis at 120 months (P = 2.98e-3). Conclusion: Our study found that the MLH1 gene was associated with the worst prognosis in CRC with a median survival of 38 months. This study may provide insight into targeted therapies for CRC and improve the prognosis of these patients.

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