Mambetsariev Isa, Mirzapoiazova Tamara, Lennon Frances, Jolly Mohit Kumar, Li Haiqing, Nasser Mohd W, Vora Lalit, Kulkarni Prakash, Batra Surinder K, Salgia Ravi
City of Hope, Dept. of Medical Oncology and Therapeutics Research, Duarte, CA 91010, USA.
Abbott Molecular, Des Plaines, IL 60018, USA.
J Clin Med. 2019 Jul 16;8(7):1038. doi: 10.3390/jcm8071038.
Small cell lung cancer (SCLC) is an aggressive neuroendocrine disease with an overall 5 year survival rate of ~7%. Although patients tend to respond initially to therapy, therapy-resistant disease inevitably emerges. Unfortunately, there are no validated biomarkers for early-stage SCLC to aid in early detection. Here, we used readouts of lesion image characteristics and cancer morphology that were based on fractal geometry, namely fractal dimension (FD) and lacunarity (LC), as novel biomarkers for SCLC. Scanned tumors of patients before treatment had a high FD and a low LC compared to post treatment, and this effect was reversed after treatment, suggesting that these measurements reflect the initial conditions of the tumor, its growth rate, and the condition of the lung. Fractal analysis of mitochondrial morphology showed that cisplatin-treated cells showed a discernibly decreased LC and an increased FD, as compared with control. However, treatment with mdivi-1, the small molecule that attenuates mitochondrial division, was associated with an increase in FD as compared with control. These data correlated well with the altered metabolic functions of the mitochondria in the diseased state, suggesting that morphological changes in the mitochondria predicate the tumor's future ability for mitogenesis and motogenesis, which was also observed on the CT scan images. Taken together, FD and LC present ideal tools to differentiate normal tissue from malignant SCLC tissue as a potential diagnostic biomarker for SCLC.
小细胞肺癌（SCLC）是一种侵袭性神经内分泌疾病，总体5年生存率约为7%。尽管患者最初往往对治疗有反应，但不可避免地会出现治疗抵抗性疾病。不幸的是，目前尚无经过验证的早期SCLC生物标志物来辅助早期检测。在此，我们将基于分形几何的病变图像特征和癌症形态学读数，即分形维数（FD）和孔隙率（LC），用作SCLC的新型生物标志物。与治疗后相比，治疗前患者的扫描肿瘤具有高FD和低LC，且这种效应在治疗后发生逆转，这表明这些测量反映了肿瘤的初始状态、生长速率以及肺部状况。线粒体形态的分形分析表明，与对照组相比，顺铂处理的细胞显示出明显降低的LC和增加的FD。然而，与对照组相比，用可减弱线粒体分裂的小分子mdivi-1处理与FD增加相关。这些数据与患病状态下线粒体代谢功能的改变密切相关，表明线粒体的形态变化预示着肿瘤未来的有丝分裂和运动发生能力，这在CT扫描图像上也得到了观察。综上所述，FD和LC是区分正常组织与恶性SCLC组织的理想工具，可作为SCLC潜在的诊断生物标志物。
