Circulating Genetically Abnormal Cells Add Non-Invasive Diagnosis Value to Discriminate Lung Cancer in Patients With Pulmonary Nodules ≤10 mm

Maosong Ye; Xiaoxuan Zheng; Xin Ye; Juncheng Zhang; Chuoji Huang; Zilong Liu; Meng Huang; Xianjun Fan; Yanci Chen; Botao Xiao; Jiayuan Sun; Chunxue Bai

doi:10.3389/fonc.2021.638223

Circulating Genetically Abnormal Cells Add Non-Invasive Diagnosis Value to Discriminate Lung Cancer in Patients With Pulmonary Nodules ≤10 mm

Front Oncol. 2021 Mar 11:11:638223. doi: 10.3389/fonc.2021.638223. eCollection 2021.

Authors

Maosong Ye¹, Xiaoxuan Zheng^{2

3}, Xin Ye^{4

5

6}, Juncheng Zhang^{4

5}, Chuoji Huang^{4

5}, Zilong Liu¹, Meng Huang^{4

5}, Xianjun Fan^{4

5}, Yanci Chen^{4

5}, Botao Xiao⁶, Jiayuan Sun^{2

3}, Chunxue Bai¹

Affiliations

¹ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Respiratory Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁴ Joint Research Center of Liquid Biopsy in Guangdong, Hong Kong, and Macao, Zhuhai, China.
⁵ Zhuhai Sanmed Biotech Ltd., Zhuhai, China.
⁶ School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.

Abstract

Background: Lung cancer screening using low-dose computed tomography (LDCT) often leads to unnecessary biopsy because of the low specificity among patients with pulmonary nodules ≤10 mm. Circulating genetically abnormal cells (CACs) can be used to discriminate lung cancer from benign lung disease. To examine the diagnostic value of CACs in detecting lung cancer for patients with malignant pulmonary nodules ≤10 mm.

Methods: In this prospective study, patients with pulmonary nodules ≤10 mm who were detected at four hospitals in China from January 2019 to January 2020 were included. CACs were detected using fluorescence in-situ hybridization. All patients were confirmed as lung cancer or benign disease by further histopathological examination. Multivariable logistic regression models were established to detect the presence of lung cancer using CACs and other associated characteristics. Receiver operating characteristic analysis was used to evaluate the performance of CACs for lung cancer diagnosis.

Results: Overall, 125 patients were included and analyzed. When the cutoff value of CACs was >2, the sensitivity and specificity for lung cancer were 70.5 and 86.4%. Male (OR = 0.330, P = 0.005), maximum solid nodule (OR = 2.362, P = 0.089), maximum nodule located in upper lobe (OR = 3.867, P = 0.001), and CACs >2 (OR = 18.525, P < 0.001) met the P < 0.10 criterion for inclusion in the multivariable models. The multivariable logistic regression model that included the dichotomized CACs (>2 vs. ≤2) and other clinical factors (AUC = 0.907, 95% CI = 0.842-0.951) was superior to the models that only considered dichotomized CACs or other clinical factors and similar to the model with numerical CACs and other clinical factors (AUC = 0.913, 95% CI = 0.850-0.956).

Conclusion: CACs presented a significant diagnostic value in detecting lung cancer for patients with pulmonary nodules ≤10 mm.

Keywords: circulating genetically abnormal cell (CAC); early detection; early diagnosis; lung cancer; pulmonary nodule.