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

Abstract Background To 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 scarc...

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Autores principales:	Yusuke Takanashi, Kazuhito Funai, Fumihiro Eto, Kiyomichi Mizuno, Akikazu Kawase, Hong Tao, Takuya Kitamoto, Yutaka Takahashi, Haruhiko Sugimura, Mitsutoshi Setou, Tomoaki Kahyo, Norihiko Shiiya
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Lung squamous cell carcinoma Prognostic factor Recurrence prediction Lipid Mass spectrometry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1b4093d545914752b6aad0fa3c4d2dff
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spelling	oai:doaj.org-article:1b4093d545914752b6aad0fa3c4d2dff2021-11-21T12:30:16ZDecreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study10.1186/s12885-021-08948-51471-2407https://doaj.org/article/1b4093d545914752b6aad0fa3c4d2dff2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08948-5https://doaj.org/toc/1471-2407Abstract Background To 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. Methods Recurrent (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. Results Among 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. Conclusion We 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 registration This retrospective study was registered at the UMIN Clinical Trial Registry ( UMIN000039202 ) on January 21, 2020.Yusuke TakanashiKazuhito FunaiFumihiro EtoKiyomichi MizunoAkikazu KawaseHong TaoTakuya KitamotoYutaka TakahashiHaruhiko SugimuraMitsutoshi SetouTomoaki KahyoNorihiko ShiiyaBMCarticleLung squamous cell carcinomaPrognostic factorRecurrence predictionLipidMass spectrometryNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lung squamous cell carcinoma Prognostic factor Recurrence prediction Lipid Mass spectrometry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Lung squamous cell carcinoma Prognostic factor Recurrence prediction Lipid Mass spectrometry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yusuke Takanashi Kazuhito Funai Fumihiro Eto Kiyomichi Mizuno Akikazu Kawase Hong Tao Takuya Kitamoto Yutaka Takahashi Haruhiko Sugimura Mitsutoshi Setou Tomoaki Kahyo Norihiko Shiiya Decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study
description	Abstract Background To 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. Methods Recurrent (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. Results Among 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. Conclusion We 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 registration This retrospective study was registered at the UMIN Clinical Trial Registry ( UMIN000039202 ) on January 21, 2020.
format	article
author	Yusuke Takanashi Kazuhito Funai Fumihiro Eto Kiyomichi Mizuno Akikazu Kawase Hong Tao Takuya Kitamoto Yutaka Takahashi Haruhiko Sugimura Mitsutoshi Setou Tomoaki Kahyo Norihiko Shiiya
author_facet	Yusuke Takanashi Kazuhito Funai Fumihiro Eto Kiyomichi Mizuno Akikazu Kawase Hong Tao Takuya Kitamoto Yutaka Takahashi Haruhiko Sugimura Mitsutoshi Setou Tomoaki Kahyo Norihiko Shiiya
author_sort	Yusuke Takanashi
title	Decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study
title_short	Decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study
title_full	Decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study
title_fullStr	Decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study
title_full_unstemmed	Decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study
title_sort	decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study
publisher	BMC
publishDate	2021
url	https://doaj.org/article/1b4093d545914752b6aad0fa3c4d2dff
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Decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study

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