Abstract
Abstract Introduction: Bladder cancer (BlCa) ranks as the sixth most prevalent cancer in the world. A number of urine based BlCa detection tests have recently been approved for clinical use, including the NMP22 tests and the bladder tumor antigen (BTA) tests for both detection and monitoring of patients with known bladder cancer. The FDA have approved them both for surveillance in BlCa only in conjunction with cystoscopy. Unfortunately, the sensitivity and specificity of these tests are poor, and cannot distinguish between aggressive and non-aggressive tumors. This project aims to identify alternate markers that can overcome these drawbacks. Methods: We characterized the global metabolome of 47 bladder tumors retrieved by radical cystectomy (RC) or TURBT, including 14 specimens with matching plasma and serum samples. All specimens were subjected to untargeted metabolomic approaches with gas chromatography- time-of-flight mass spectrometry (GC-TOF MS) to profile primary metabolites, hydrophilic interaction liquid chromatography MS (HILIC-QTOF MS) to profile biogenic amines, and liquid chromatography charged surface hybrid MS (LC-CSH-QTOF MS) to characterize complex lipids. Differentially expressed metabolites were analyzed with respect to grade, stage, metastases, and the use of neoadjuvant chemotherapy. For selected metabolites, area under the ROC curve (AUC) is calculated as % sensitivity vs. 100% specificity. Expression of highly discriminatory metabolites were then validated in the plasma and serum samples to determine which forum would provide greater specificity. Results: We first assembled a discovery cohort of 33 patients who did not have matching blood specimen for primary metabolites, biogenic amines and complex lipids. Comparison of high vs low grade tumors yielded two lipids, a sphingomyelin (SM (d38) and a phosphatidylcholine PC(p-38), that were significantly different (adjusted p-value<0.05, log2fold change>2.5). These results were validated in the 14-sample cohort with matching plasma and serum of which the latter showed significant correlation between tumor and plasma (Spearman R=0.872, adj p=0.03). Conclusions: Our results indicate that certain sphingomyelins and phosphatidylcholines may be useful as plasma markers of high grade BlCa. Further analyses are required to evaluate whether these markers are more discriminatory compared to existing urinary markers. Citation Format: Maria-Malvina Tsamouri, Akshaya Karthikeyan, Christopher A. Lucchesi, Blythe P. Durbin-Johnson, Marc A. Dall'Era, Paramita M. Ghosh. Tumor, serum and plasma metabolome in patients with high-grade bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4765.
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