Brominska Barbara, Gabryel Piotr, Jarmołowska-Jurczyszyn Donata, Janicka-Jedyńska Małgorzata, Kluk Andrzej, Trojanowski Maciej, Brajer-Luftmann Beata, Woliński Kosma, Czepczyński Rafał, Gut Paweł, Bromiński Gabriel, Majewski Przemysław, Dyszkiewicz Wojciech, Ruchała Marek
Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland.
Department of Thoracic Surgery, Poznan University of Medical Sciences, Poznan, Poland.
Arch Med Sci. 2019 Jul;15(4):1010-1016. doi: 10.5114/aoms.2018.75889. Epub 2018 Jun 1.
Klotho has been recently described as a carcinogenesis suppressor. Large cell neuroendocrine lung carcinoma (LCNEC) is a rare, highly malignant neoplasm. In the light of increasing incidence of neuroendocrine tumours, biomarkers predicting survival are needed. We consider that Klotho might be one.
We analysed records of all patients diagnosed with LCNEC, atypical carcinoid and typical carcinoid operated on in our institution between 2007 and 2015. Initially, we found 134 cases. Forty-six specimens were unattainable and thus excluded from research. All patients diagnosed with LCNEC according to the WHO classification were included in the study. Immunohistochemical staining for Klotho was performed. We retrospectively reviewed patient charts and analysed multiple variables.
Positive staining for Klotho was present in 36 tissue specimens, while 12 patients were Klotho-negative. Survival length was significantly higher in Klotho-positive cases ( = 0.024), while advanced nodal status (N1 and N2) represented a marker of poor outcome ( = 0.011). In multivariate analysis, both Klotho presence ( = 0.015; HR = 0.37; 95% CI: 0.17-0.86) and nodal involvement ( = 0.007; HR = 3.04; 95% CI: 1.37-6.82) were independent prognostic factors. Tumour vessel invasion and visceral pleura infiltration were not associated with worse treatment results. Klotho presence predicted a favourable prognosis in these groups ( = 0.018; = 0.007).
Our results suggest that Klotho might be a positive factor for predicting survival in LCNEC and nodal involvement a negative one. Thus, these two markers may assist in the selection of subjects with unfavourable prognosis and to personalise therapy regimens.
最近，klotho被描述为一种致癌作用抑制因子。大细胞神经内分泌肺癌（LCNEC）是一种罕见的高恶性肿瘤。鉴于神经内分泌肿瘤的发病率不断上升，需要能够预测生存情况的生物标志物。我们认为klotho可能是其中之一。
我们分析了2007年至2015年间在我们机构接受手术的所有诊断为LCNEC、非典型类癌和典型类癌患者的记录。最初，我们发现了134例病例。46个标本无法获取，因此被排除在研究之外。所有根据世界卫生组织分类诊断为LCNEC的患者均纳入研究。进行了klotho的免疫组织化学染色。我们回顾性地查阅了患者病历并分析了多个变量。
36个组织标本中klotho染色呈阳性，而12例患者klotho呈阴性。klotho阳性病例的生存长度显著更高（P = 0.024），而晚期淋巴结状态（N1和N2）是预后不良的一个标志（P = 0.011）。在多变量分析中，klotho的存在（P = 0.015；HR = 0.37；95%CI：0.17 - 0.86）和淋巴结受累情况（P = 0.007；HR = 3.04；95%CI：1.37 - 6.82）均为独立的预后因素。肿瘤血管侵犯和脏层胸膜浸润与较差的治疗结果无关。klotho的存在在这些组中预示着良好的预后（P = 0.018；P = 0.007）。
我们的结果表明，klotho可能是预测LCNEC生存情况的一个积极因素，而淋巴结受累是一个消极因素。因此，这两个标志物可能有助于选择预后不良的患者并使治疗方案个性化。
