Decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study

BMC Cancer

Takuya Kitamoto¹  Fumihiro Eto²  Yusuke Takanashi³  Tomoaki Kahyo⁴  Yutaka Takahashi⁵  Mitsutoshi Setou⁶  Hong Tao⁷  Haruhiko Sugimura⁷  Kiyomichi Mizuno⁸  Norihiko Shiiya⁸  Akikazu Kawase⁸  Kazuhito Funai⁸ 

[1] Advanced Research Facilities & Services, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;International Mass Imaging Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;Preppers Co. Ltd., 1-23-17 Kitashinagawa, Shinagawa Ward, 140-0001, Tokyo, Japan;Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;Preppers Co. Ltd., 1-23-17 Kitashinagawa, Shinagawa Ward, 140-0001, Tokyo, Japan;International Mass Imaging Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Systems Molecular Anatomy, Institute for Medical Photonics Research, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, 431-3192, Shizuoka, Japan;

关键词: Lung squamous cell carcinoma;    Prognostic factor;    Recurrence prediction;    Lipid;    Mass spectrometry;   

DOI  :  10.1186/s12885-021-08948-5

来源: Springer

【 摘 要 】

BackgroundTo reduce disease recurrence after radical surgery for lung squamous cell carcinomas (SQCCs), accurate prediction of recurrent high-risk patients is required for efficient patient selection for adjuvant chemotherapy. Because treatment modalities for recurrent lung SQCCs are scarce compared to lung adenocarcinomas (ADCs), accurately selecting lung SQCC patients for adjuvant chemotherapy after radical surgery is highly important. Predicting lung cancer recurrence with high objectivity is difficult with conventional histopathological prognostic factors; therefore, identification of a novel predictor is expected to be highly beneficial. Lipid metabolism alterations in cancers are known to contribute to cancer progression. Previously, we found that increased sphingomyelin (SM)(d35:1) in lung ADCs is a candidate for an objective recurrence predictor. However, no lipid predictors for lung SQCC recurrence have been identified to date. This study aims to identify candidate lipid predictors for lung SQCC recurrence after radical surgery.MethodsRecurrent (n = 5) and non-recurrent (n = 6) cases of lung SQCC patients who underwent radical surgery were assigned to recurrent and non-recurrent groups, respectively. Extracted lipids from frozen tissue samples of primary lung SQCC were analyzed by liquid chromatography-tandem mass spectrometry. Candidate lipid predictors were screened by comparing the relative expression levels between the recurrent and non-recurrent groups. To compare lipidomic characteristics associated with recurrent SQCCs and ADCs, a meta-analysis combining SQCC (n = 11) and ADC (n = 20) cohorts was conducted.ResultsAmong 1745 screened lipid species, five species were decreased (≤ 0.5 fold change; P < 0.05) and one was increased (≥ 2 fold change; P < 0.05) in the recurrent group. Among the six candidates, the top three final candidates (selected by AUC assessment) were all decreased SM(t34:1) species, showing strong performance in recurrence prediction that is equivalent to that of histopathological prognostic factors. Meta-analysis indicated that decreases in a limited number of SM species were observed in the SQCC cohort as a lipidomic characteristic associated with recurrence, in contrast, significant increases in a broad range of lipids (including SM species) were observed in the ADC cohort.ConclusionWe identified decreased SM(t34:1) as a novel candidate predictor for lung SQCC recurrence. Lung SQCCs and ADCs have opposite lipidomic characteristics concerning for recurrence risk.Trial registrationThis retrospective study was registered at the UMIN Clinical Trial Registry (UMIN000039202) on January 21, 2020.

【 授权许可】

CC BY