Abstract
ObjectiveThe size distribution of circulating aneuploid cells (CACs) and its clinical significance were investigated in resectable non-small cell lung cancer (NSCLC).Patients and MethodsA total of 50 patients with resectable NSCLC were enrolled in this study. Blood samples (50 pre-surgery and 35 post-surgery) were collected and used for the detection of CAC chromosome 8 heteroploidy through the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method.ResultsLess than 20% small cell size and more than 80% large cell size CACs were detected. Karyotypes, including triploid, tetraploid, and multiploid, had varying distributions. The triploid subtype accounted for the majority of small cell size CACs, whereas the multiploid subtype accounted for the majority of large cell size CACs. We found that total small cell size and triploid small cell size CACs, but not large cell size CACs, derived from pre-surgery samples, were associated with shorter disease-free survival. Moreover, total small cell size and triploid small cell size CACs were associated with higher TNM stage and recurrence. Nevertheless, the variation between pre- and post-surgery CACs was not related to survival among patients with resectable NSCLC.ConclusionsPre-surgery small cell size CACs, especially the triploid subtype, could be regarded as a potential prognostic biomarker for patients with resectable NSCLC.
Highlights
Lung cancer is the leading cause of cancer-associated death worldwide [1]
The triploid subtype accounted for the majority of small cell size circulating aneuploid cells (CACs), whereas the multiploid subtype accounted for the majority of large cell size CACs
We found that total small cell size and triploid small cell size CACs, but not large cell size CACs, derived from pre-surgery samples, were associated with shorter disease-free survival
Summary
Lung cancer is the leading cause of cancer-associated death worldwide [1]. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases, with a low 5-year survival rate of less than 20% [2,3,4]. CTCs, CECs, and CACs are well-known for their association with metastasis and progression and provide information for individual therapy and prediction of prognosis in several cancer types such as breast, colorectal, prostate, and lung [7, 12,13,14,15,16,17] Epithelial markers such as EpCAM and cytokeratin are often used to enrich CTCs [18]. This approach may miss an aggressive and clinically relevant subpopulation of tumor cells, partially because of the epithelial-mesenchymal transition (EMT) that occurs with a reduction in or loss of epithelial markers in the tumors [19, 20] This kind of EMT+ CTC is helpful in predicting poor outcome and managing therapy, which is important for patients [19]. CTCs are a heterogeneous population; clarification of its characteristics can shed light on tumor heterogeneity, recurrence mechanism, treatment efficacy, or poor prognosis for cancer patients [21, 22]
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