Advanced Lung Disease and Transplant Program, INOVA Fairfax Hospital, Falls Church, Virginia USA.
Pulmonary Medicine Department, Meir Medical Center, Kfar Saba, Israel.
Thorac Cancer. 2019 Apr;10(4):1009-1015. doi: 10.1111/1759-7714.13026. Epub 2019 Mar 12.
A ground glass opacity (GGO) lung lesion may represent early stage adenocarcinoma, which has an excellent prognosis upon prompt surgical resection. However, GGO lesions have broad differential diagnoses, including both benign and malignant lesions. Our objective was to study telomere length and telomerase activity in patients with suspected lung cancer in which GGO was the predominant radiographic feature. Knowledge of telomere biology may help distinguish malignant from benign radiographic lesions and guide risk assessment of these lesions. Peripheral blood samples were taken from 22 patients with suspected adenocarcinoma with the GGO radiographic presentation. Multidisciplinary discussion confirmed the need for surgery in all cases. We used an age and gender-matched group without known lung disease as a control. Telomere length and aggregates were assessed by quantitative fluorescence in situ hybridization (QFISH) and quantitative PCR. Cell senescence was evaluated by senescence-associated heterochromatin foci. Subjects with GGO lesions had a higher percentage of lymphocytes with shorter telomeres (Q-FISH, P = 0.003). Furthermore, relative telomere length was also reduced among the GGO cases (qPCR, P < 0.05). Increased senescence was observed in the GGO group compared to controls (P < 0.001), with significant correlation between the senescence-associated heterochromatin foci and aggregate formation (r = -0.7 and r = -0.44 for cases and controls, respectively). In conclusion, patients with resectable early adenocarcinoma demonstrate abnormal telomere length and cell senescence in peripheral blood leukocytes compared to control subjects. Abnormal telomere biology in the peripheral blood may increase suspicion of early adenocarcinoma among patients with GGO lesions.
磨玻璃密度（GGO）肺部病变可能代表早期腺癌，及时进行手术切除可获得良好的预后。然而，GGO 病变具有广泛的鉴别诊断，包括良性和恶性病变。我们的目的是研究以 GGO 为主要影像学特征的疑似肺癌患者的端粒长度和端粒酶活性。对端粒生物学的了解可能有助于区分恶性和良性影像学病变，并指导这些病变的风险评估。从 22 名疑似 GGO 表现为主的腺癌患者中采集外周血样本。多学科讨论确认所有病例均需手术。我们使用年龄和性别匹配、无已知肺部疾病的患者作为对照。通过定量荧光原位杂交（QFISH）和定量 PCR 评估端粒长度和聚集物。通过衰老相关异染色质焦点评估细胞衰老。GGO 病变患者具有更多淋巴细胞、较短端粒的百分比（Q-FISH，P=0.003）。此外，GGO 病例的相对端粒长度也降低（qPCR，P<0.05）。与对照组相比，GGO 组观察到更多的衰老细胞（P<0.001），衰老相关异染色质焦点与聚集物形成之间存在显著相关性（病例和对照组分别为 r=-0.7 和 r=-0.44）。总之，与对照组相比，可切除的早期腺癌患者在外周血白细胞中表现出异常的端粒长度和细胞衰老。外周血中异常的端粒生物学可能会增加对 GGO 病变患者早期腺癌的怀疑。
