Combination of CT and telomerase-positive circulating tumor cells improves diagnosis of small pulmonary nodules

Abstract

BACKGROUND Early diagnosis and treatment are key to the long-term survival of lung cancer patients. Although CT has significantly contributed to the early diagnosis of lung cancer, there are still consequences of excessive or delayed treatment. By improving the sensitivity and specificity of circulating tumor cell (CTC) detection, a solution was proposed for differentiating benign from malignant pulmonary nodules. METHODS In this study, we used telomerase reverse transcriptase–based (TERT-based) CTC detection (TBCD) to distinguish benign from malignant pulmonary nodules < 2 cm and compared this method with the pathological diagnosis as the gold standard. FlowSight and FISH were used to confirm the CTCs detected by TBCD. RESULTS Our results suggest that CTCs based on TBCD can be used as independent biomarkers to distinguish benign from malignant nodules and are significantly superior to serum tumor markers. When the detection threshold was 1, the detection sensitivity and specificity of CTC diagnosis were 0.854 and 0.839, respectively. For pulmonary nodules ≤ 1 cm and 1–2 cm, the sensitivity and specificity of CTCs were both higher than 77%. Additionally, the diagnostic ability of CTC-assisted CT was compared by CT detection. The results show that CT combined with CTCs could significantly improve the differentiation ability of benign and malignant nodules in lung nodules < 2 cm and that the sensitivity and specificity could reach 0.899 and 0.839, respectively. CONCLUSION TBCD can effectively diagnose pulmonary nodules and be used as an effective auxiliary diagnostic scheme for CT diagnosis. FUNDING National Key Research and Development Project grant nos. 2019YFC1315700 and 2017YFC1308702, CAMS Initiative for Innovative Medicine grant no. 2017-I2M-1-005, and National Natural Science Foundation of China grant no. 81472013.

Telomerase positive CTCs with PSMA high expression associated with prostate cancer metastasis

“…The oHSV1-hTERTp-GFP was designed by replacing the endogenous ICP4 promoter with a TERT promoter and replacing the genes encoding cell protein 34.5 (ICP34.5) with a GFP gene as described before (7,8). The purified viruses were stored at −80 ℃ until use.…”

“…Collected 4 milliliters of prebiopsy PB with ethylene diamine tetraacetic acid (EDTA) tubes and kept them at 4 ℃ until separation. Sample preparation and detailed workflow were carried out as previously described (7,8). In brief, the oHSV1-hTERTp-GFP was used to infect the cells after lysis of red blood cells, then infected cells were incubated at 5% CO 2 and 37 ℃ cell incubator for 24 h. The transduced cells were collected, then stained with an anti-CD45 antibody (Biolegend, San Diego, CA, USA; Cat: 304014) and anti-PSMA antibody (Biolegend, Cat: 342508).…”

“…CTCs have been reported to detect tumor metastasis and prognosis among those patients, which could be an ideal biomarker for PCa metastasis management (4)(5)(6). We have previously established a telomerase reverse transcriptase (TERT)based CTC detection (TBCD) method and showed a high sensitivity in lung cancer diagnosis (7,8). High telomerase activity plays a crucial role in the high division activity of cancer cells, and this approach could enrich and separate viable tumor cells with high proliferation ability (9,10).…”

Editorial for “Different Attenuation Models of Diffusion‐Weighted Imaging for the Differentiation of Benign and Malignant Musculoskeletal Tumors: A Volumetric in Addition to the Standard Approach”

“…In the present study, 4 although the authors found that the multiparametric approach did not improve the diagnostic performance of the K parameter, the study was headed in the right direction. Moreover, it is worth mentioning that combined imaging techniques and serological markers, such as circulating tumor cells or tumor markers, have been a popular approach in tumor diagnosis due to their unique advantages 7,8 . Therefore, except for the combination of imaging parameters, magnetic resonance imaging (MRI) methods combined with serological markers are expected to become a novel strategy for differentiating benign and malignant musculoskeletal tumors.…”

“…Moreover, it is worth mentioning that combined imaging techniques and serological markers, such as circulating tumor cells or tumor markers, have been a popular approach in tumor diagnosis due to their unique advantages. 7,8 Therefore, except for the combination of imaging parameters, magnetic resonance imaging (MRI) methods combined with serological markers are expected to become a novel strategy for differentiating benign and malignant musculoskeletal tumors. In addition, as artificial intelligence techniques continue to develop, radiomics has shown a great potential in cancer diagnosis, prognosis, and treatment.…”