Lung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profile
Abstract In patients with unresectable non-small cell lung cancer, histological diagnosis is frequently based on small biopsy specimens unsuitable for histological diagnosis when they are severely crushed and do not retain their morphology. Therefore, establishing a novel diagnostic method independe...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-07-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-37848-w |
| _version_ | 1797769532087992320 |
|---|---|
| author | Takashi Yamashita Yusuke Takanashi Asuka Uebayashi Mikako Oka Kiyomichi Mizuno Akikazu Kawase Soho Oyama Takuya Kitamoto Minako Kondo Shiho Omori Hong Tao Yutaka Takahashi Takumi Sakamoto Tomoaki Kahyo Haruhiko Sugimura Mitsutoshi Setou Norihiko Shiiya Kazuhito Funai |
| author_facet | Takashi Yamashita Yusuke Takanashi Asuka Uebayashi Mikako Oka Kiyomichi Mizuno Akikazu Kawase Soho Oyama Takuya Kitamoto Minako Kondo Shiho Omori Hong Tao Yutaka Takahashi Takumi Sakamoto Tomoaki Kahyo Haruhiko Sugimura Mitsutoshi Setou Norihiko Shiiya Kazuhito Funai |
| author_sort | Takashi Yamashita |
| collection | DOAJ |
| description | Abstract In patients with unresectable non-small cell lung cancer, histological diagnosis is frequently based on small biopsy specimens unsuitable for histological diagnosis when they are severely crushed and do not retain their morphology. Therefore, establishing a novel diagnostic method independent of tissue morphology or conventional immunohistochemistry (IHC) markers is required. We analyzed the lipid profiles of resected primary lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) specimens using liquid chromatography-tandem mass spectrometry. The specimens of 26 ADC and 18 SQCC cases were evenly assigned to the discovery and validation cohorts. Non-target screening on the discovery cohort identified 96 and 13 lipid peaks abundant in ADC and SQCC, respectively. Among these 109 lipid peaks, six and six lipid peaks in ADC and SQCC showed reproducibility in target screening on the validation cohort. Finally, we selected three and four positive lipid markers for ADC and SQCC, demonstrating high discrimination abilities. In cases difficult to diagnose by IHC staining, [cardiolipin(18:2_18:2_18:2_18:2)-H]− and [triglyceride(18:1_17:1_18:1) + NH4]+ showed the excellent diagnostic ability for ADC (sensitivity: 1.00, specificity: 0.89, accuracy: 0.93) and SQCC (sensitivity: 0.89, specificity: 0.83, accuracy: 0.87), respectively. These novel candidate lipid markers may contribute to a more accurate diagnosis and subsequent treatment strategy for unresectable NSCLC. |
| first_indexed | 2024-03-12T21:10:26Z |
| format | Article |
| id | doaj.art-e00a28344bf0464d98235353aafd471d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T21:10:26Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e00a28344bf0464d98235353aafd471d2023-07-30T11:15:02ZengNature PortfolioScientific Reports2045-23222023-07-0113111010.1038/s41598-023-37848-wLung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profileTakashi Yamashita0Yusuke Takanashi1Asuka Uebayashi2Mikako Oka3Kiyomichi Mizuno4Akikazu Kawase5Soho Oyama6Takuya Kitamoto7Minako Kondo8Shiho Omori9Hong Tao10Yutaka Takahashi11Takumi Sakamoto12Tomoaki Kahyo13Haruhiko Sugimura14Mitsutoshi Setou15Norihiko Shiiya16Kazuhito Funai17First Department of Surgery, Hamamatsu University School of MedicineFirst Department of Surgery, Hamamatsu University School of MedicineFirst Department of Surgery, Hamamatsu University School of MedicineFirst Department of Surgery, Hamamatsu University School of MedicineFirst Department of Surgery, Hamamatsu University School of MedicineFirst Department of Surgery, Hamamatsu University School of MedicineDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of MedicineAdvanced Research Facilities and Services, Hamamatsu University School of MedicineAdvanced Research Facilities and Services, Hamamatsu University School of MedicineDepartment of Tumor Pathology, Hamamatsu University School of MedicineDepartment of Tumor Pathology, Hamamatsu University School of MedicineDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of MedicineDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of MedicineDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of MedicineDepartment of Tumor Pathology, Hamamatsu University School of MedicineDepartment of Cellular and Molecular Anatomy, Hamamatsu University School of MedicineFirst Department of Surgery, Hamamatsu University School of MedicineFirst Department of Surgery, Hamamatsu University School of MedicineAbstract In patients with unresectable non-small cell lung cancer, histological diagnosis is frequently based on small biopsy specimens unsuitable for histological diagnosis when they are severely crushed and do not retain their morphology. Therefore, establishing a novel diagnostic method independent of tissue morphology or conventional immunohistochemistry (IHC) markers is required. We analyzed the lipid profiles of resected primary lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) specimens using liquid chromatography-tandem mass spectrometry. The specimens of 26 ADC and 18 SQCC cases were evenly assigned to the discovery and validation cohorts. Non-target screening on the discovery cohort identified 96 and 13 lipid peaks abundant in ADC and SQCC, respectively. Among these 109 lipid peaks, six and six lipid peaks in ADC and SQCC showed reproducibility in target screening on the validation cohort. Finally, we selected three and four positive lipid markers for ADC and SQCC, demonstrating high discrimination abilities. In cases difficult to diagnose by IHC staining, [cardiolipin(18:2_18:2_18:2_18:2)-H]− and [triglyceride(18:1_17:1_18:1) + NH4]+ showed the excellent diagnostic ability for ADC (sensitivity: 1.00, specificity: 0.89, accuracy: 0.93) and SQCC (sensitivity: 0.89, specificity: 0.83, accuracy: 0.87), respectively. These novel candidate lipid markers may contribute to a more accurate diagnosis and subsequent treatment strategy for unresectable NSCLC.https://doi.org/10.1038/s41598-023-37848-w |
| spellingShingle | Takashi Yamashita Yusuke Takanashi Asuka Uebayashi Mikako Oka Kiyomichi Mizuno Akikazu Kawase Soho Oyama Takuya Kitamoto Minako Kondo Shiho Omori Hong Tao Yutaka Takahashi Takumi Sakamoto Tomoaki Kahyo Haruhiko Sugimura Mitsutoshi Setou Norihiko Shiiya Kazuhito Funai Lung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profile Scientific Reports |
| title | Lung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profile |
| title_full | Lung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profile |
| title_fullStr | Lung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profile |
| title_full_unstemmed | Lung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profile |
| title_short | Lung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profile |
| title_sort | lung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profile |
| url | https://doi.org/10.1038/s41598-023-37848-w |
| work_keys_str_mv | AT takashiyamashita lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT yusuketakanashi lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT asukauebayashi lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT mikakooka lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT kiyomichimizuno lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT akikazukawase lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT sohooyama lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT takuyakitamoto lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT minakokondo lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT shihoomori lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT hongtao lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT yutakatakahashi lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT takumisakamoto lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT tomoakikahyo lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT haruhikosugimura lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT mitsutoshisetou lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT norihikoshiiya lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile AT kazuhitofunai lungadenocarcinomaandsquamouscellcarcinomadifficultforimmunohistochemicaldiagnosiscanbedistinguishedbylipidprofile |