First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka, 431-3192, Japan.
Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka, 431-3192, Japan.
Sci Rep. 2023 Jul 26;13(1):12092. doi: 10.1038/s41598-023-37848-w.
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.
在不可切除的非小细胞肺癌患者中，组织学诊断通常基于严重挤压且无法保留形态的小活检标本，这些标本不适合组织学诊断。因此，需要建立一种新的诊断方法，该方法不依赖于组织形态或传统的免疫组织化学（IHC）标志物。我们使用液相色谱-串联质谱法分析了切除的原发性肺腺癌（ADC）和鳞状细胞癌（SQCC）标本的脂质谱。将 26 例 ADC 和 18 例 SQCC 标本均匀分配到发现和验证队列中。在发现队列上进行非靶向筛选，分别在 ADC 和 SQCC 中鉴定出 96 个和 13 个脂质峰。在这 109 个脂质峰中，在验证队列上进行靶向筛选时，ADC 和 SQCC 中有 6 个和 6 个脂质峰具有重现性。最后，我们选择了三个和四个阳性脂质标志物用于 ADC 和 SQCC，证明具有较高的鉴别能力。在难以通过 IHC 染色诊断的情况下，[二己酰基磷脂酰甘油（18:2_18:2_18:2_18:2）-H]和[三油酰甘油（18:1_17:1_18:1）+NH4]分别对 ADC（灵敏度：1.00，特异性：0.89，准确性：0.93）和 SQCC（灵敏度：0.89，特异性：0.83，准确性：0.87）具有出色的诊断能力。这些新型候选脂质标志物可能有助于更准确地诊断不可切除的 NSCLC，并制定随后的治疗策略。
