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

Abstract

BackgroundLung 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.MethodsIn 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.ResultsOverall, 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).ConclusionCACs presented a significant diagnostic value in detecting lung cancer for patients with pulmonary nodules ≤10 mm.

Diagnostic value of circulating genetically abnormal cells to support computed tomography for benign and malignant pulmonary nodules

“…Moreover, the diagnostic value of CACs in comparison with other traditional biomarkers has been confirmed using a cohort of patients with lung nodules, which is an independent validation to the work conducted by Ye et al [ 24 ]. In the present study, the highest diagnostic efficiency was achieved when a CAC counts of 3 was chosen as the cut-off value, this result is similar to the study conducted by Qiu [ 25 ] and Ye [ 18 ] et al Overall, CAC counts presented better diagnostic value than commonly used tumour markers (CEA, CYFRA21–1, and NSE), which agrees with the results of several studies reporting the advantages of CACs for the diagnosis of lung cancer [ 17 , 18 , 24 , 25 , 27 ], CACs have the potential to become a better novel diagnostic marker of lung cancer.…”

“…Therefore, the traditional mode of small lung nodule diagnosis should be investigated. Previous works as well as this work suggest that CACs are an ideal candidate marker, as such a test only requires the simple process of blood collection and its accuracy has been reported in early lung cancer patients [ 18 , 24 , 25 ].…”

“…Katz et al also proved that CACs have auxiliary diagnostic value in different stages of lung cancer, with the latest research showing a sensitivity and specificity of 88.8% and 100%, respectively, for lung cancer diagnosis [ 17 ]. Therefore, CACs have great potential for diagnosing pulmonary nodules [ 18 ].…”

Potential clinical utility of liquid biopsy in early-stage non-small cell lung cancer

“…With the advantages of an early appearance in the disease course, cancer specificity, biological stability, and ready accessibility in bodily fluids [ 81 ], aberrant DNA methylation analysis combined with machine learning provided the opportunity to overcome the challenge of the low abundance of ctDNA in plasma samples [ 28 , 29 , 34 , 58 , 82 , 83 ]. CTCs in the blood could serve as effective screening and diagnostic markers to discriminate small malignant pulmonary nodules from benign lesions [ 54 , 56 ]. The profiling of circulating microRNAs has promising accuracy for discriminating lung cancer patients from healthy controls and could be developed as a supplement in future screening [ 51 , 84 ].…”

Editorial: Surgical Selection of Sublobar Resection and Scope of Lymph Node Dissection for Early-Stage Lung Cancer

“…Common evaluation methods include imaging, gene detection, and tumor-related marker detection. Ye et al ( 3 ) conducted a prospective study of 125 preoperative patients with NSCLC with nodules of 1 cm or less. Their analysis showed that patients with pulmonary nodules of 10 mm or less detected by circulating genetically abnormal cells (CACs) before operation could effectively diagnose lung cancer and help doctors choose the appropriate treatment.…”