A73-16 Metabolomic Profiling of Tryptophan and Indole Derivatives in Lung Cancer

Background Tryptophan metabolism and its downstream derivatives, such as indole, have been implicated in lung cancer pathogenesis. Metabolomic profiling of tumor-draining lymph nodes has emerged as a valuable tool in characterizing tumor-driven metabolic aberrations, even before metastasis occurs. Here, we profiled tryptophan and indole-related metabolites across tumor draining lymph node (TDLN), non-tumor draining lymph node (NTDLN), and plasma samples from 63 patients with non-small cell lung cancer to identify differences across these three anatomic sites. Methods We collected quantitative metabolomic data from 63 patients using an existing extraction protocol and LC mass spectrometry. The analytes of interest were L-tryptophan, D-tryptophan, and N17-dimethylindole-3-carboxyaldehyde, a downstream tryptophan byproduct. Unpaired t-tests were performed across metabolite replicates in three different sites (TDLN, NTDLN, and plasma). For each site, we evaluated for significant differences in tryptophan and indole levels across age, sex, and pathology. Results There were no significant differences observed in D-tryptophan or L-tryptophan intensities when comparing TDLN (D-tryptophan 0.031 ± 0.011; L-tryptophan 0.029 ± 0.011) and NTDLN (D-tryptophan 0.028 ± 0.007; L-tryptophan 0.026 ± 0.007) when matched for age, sex, and pathology (p = 0.363). However, significant differences were observed in N17-dimethylindole-3-carboxyaldehyde intensity levels when comparing TDLN (1.005 ± 0.034) and NTDLN (0.973 ± 0.051, p = 0.027). When metabolites were analyzed across subgroups within the same anatomic site, men were found to have higher intensities in plasma samples of D-tryptophan (1.168 ± 0.391 vs. 0.897 ± 0.231; p = 0.0004), L-tryptophan (1.171 ± 0.402 vs. 0.901 ± 0.229; p = 0.0005), and N17-dimethylindole-3-carboxyaldehyde (1.177 ± 0.341 vs. 1.038 ± 0.104; p = 0.018), men vs women respectively. N17-dimethylindole-3-carboxyaldehyde intensities were also found to differ in NTDLN when comparing men and women (0.991 ± 0.012 vs. 0.954 ± 0.062; p = 0.019) and when comparing adenocarcinoma (0.966 ± 0.053) and squamous cell carcinoma (0.993 ± 0.012, p = 0.018). Conclusions There were no significant differences observed in tryptophan levels between TDLN and NTDLN, but the increase in an indole-related derivative suggests indole may be a more reliable marker of tumor invasion. The subgroup analyses were notable for differences in men and women when comparing tryptophan and indole levels; sex-based differences in tryptophan levels have been well-established in the literature. This workflow demonstrates a methodical approach to integrating metabolomics with clinical metadata in lung carcinoma. Future steps include collecting temporal data to determine whether metabolite levels are predictive of survival. This abstract is funded by: NIH