Sphingomyelin(d35:1) as a novel predictor for lung adenocarcinoma recurrence after a radical surgery: a case-control study

BACKGROUND: To improve the postoperative prognosis of patients with lung cancer, predicting the recurrence high-risk patients is needed for the efficient application of adjuvant chemotherapy. However, predicting lung cancer recurrence after a radical surgery is difficult even with conventional histopathological prognostic factors, thereby a novel predictor should be identified. As lipid metabolism alterations are known to contribute to cancer progression, we hypothesized that lung adenocarcinomas with high recurrence risk contain candidate lipid predictors. This study aimed to identify candidate lipid predictors for the recurrence of lung adenocarcinoma after a radical surgery. METHODS: Frozen tissue samples of primary lung adenocarcinoma obtained from patients who underwent a radical surgery were retrospectively reviewed. Recurrent and non-recurrent cases were assigned to recurrent (n = 10) and non-recurrent (n = 10) groups, respectively. Extracted lipids from frozen tissue samples were subjected to liquid chromatography-tandem mass spectrometry analysis. The average total lipid levels of the non-recurrent and recurrent groups were compared. Candidate predictors were screened by comparing the folding change and P-value of t-test in each lipid species between the recurrent and non-recurrent groups. RESULTS: The average total lipid level of the recurrent group was 1.65 times higher than that of the non-recurrent group (P < 0.05). A total of 203 lipid species were increased (folding change, ≥2; P < 0.05) and 4 lipid species were decreased (folding change, ≤0.5; P < 0.05) in the recurrent group. Among these candidates, increased sphingomyelin (SM)(d35:1) in the recurrent group was the most prominent candidate predictor, showing high performance of recurrence prediction (AUC, 9.1; sensitivity, 1.0; specificity, 0.8; accuracy, 0.9). CONCLUSION: We propose SM(d35:1) as a novel candidate predictor for lung adenocarcinoma recurrence. Our finding can contribute to precise recurrence prediction and qualified postoperative therapeutic strategy for lung adenocarcinomas. TRIAL REGISTRATION: This retrospective study was registered at the UMIN Clinical Trial Registry (UMIN000039202) on 21st January 2020.