Dataset Information

Clinical significance of circulating tumor cells and tumor markers in the diagnosis of lung cancer.

ABSTRACT:

Background

Lung cancer has the highest fatality rate of all cancer types. To improve patients' survival and life quality, it is therefore very important to screen for and detect it at an early stage.

Methods

A negative enrichment-fluorescence in situ hybridization (NE-FISH) approach was used to detect circulating tumor cells (CTCs) in lung cancer patients, and levels of lung cancer-associated serum markers were also measured in the peripheral blood of these same patients. The correlation between CTCs, serum cancer markers (carcinoembryonic antigen [CEA], CA 125, CYFRA 21-1, and SCC), and clinicopathological characteristics was then investigated. Moreover, the potential clinical use of the combination of CTCs and tumor markers for the diagnosis of lung cancer, especially at early stages, was also explored.

Results

CTC frequencies in lung cancer patients were significantly higher than in healthy control volunteers or patients with benign lung disease, and the area under the receiver operating characteristics curve for the control group was 0.846 (95% CI 0.796-0.887, P < 0.001). The rate of CTC positivity in lung cancer patients was 68.29% when the CTC cutoff value was 2, and the sensitivity of this means of lung cancer detection rose to 82.93% by combining CTC-based detection with measurements of serum tumor markers. Similarly, the diagnostic sensitivity of this approach in early-stage lung cancer patients (I-II) was improved from 63.93% to 78.69%. Detection of CTCs can thus assist with the identification of benign and malignant pulmonary nodules.

Conclusions

It is potentially helpful and effective to employ a combination of CTCs and serum tumor markers for the clinical diagnosis of lung cancer.

SUBMITTER: Li Y

PROVIDER: S-EPMC6639255 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Clinical significance of circulating tumor cells and tumor markers in the diagnosis of lung cancer.

Li Yang Y Tian Xudong X Gao Lei L Jiang Xiaohong X Fu Rao R Zhang Tingting T Ren Tianying T Hu Ping P Wu Yaping Y Zhao Peige P Yang Dawei D

Cancer medicine 20190527 8

<h4>Background</h4>Lung cancer has the highest fatality rate of all cancer types. To improve patients' survival and life quality, it is therefore very important to screen for and detect it at an early stage.<h4>Methods</h4>A negative enrichment-fluorescence in situ hybridization (NE-FISH) approach was used to detect circulating tumor cells (CTCs) in lung cancer patients, and levels of lung cancer-associated serum markers were also measured in the peripheral blood of these same patients. The corr ...[more]

PMID: 31132233

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Project description:During the process of metastasis, which is the leading cause of cancer-related death, cancer cells dissociate from primary tumors, migrate to distal sites, and finally colonize, eventually leading to the formation of metastatic tumors. The migrating tumor cells in circulation, e.g., those found in peripheral blood (PB) or bone marrow (BM), are called circulating tumor cells (CTCs). CTCs in the BM are generally called disseminated tumor cells (DTCs). Many studies have reported the detection and characterization of CTCs to facilitate early diagnosis of relapse or metastasis and improve early detection and appropriate treatment decisions. Initially, epithelial markers, such as EpCAM and cytokeratins (CKs), identified using immunocytochemistry or reverse transcription polymerase chain reaction (RT-PCR) were used to identify CTCs in PB or BM. Recently, however, other markers such as human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and immuno-checkpoint genes also have been examined to facilitate detection of CTCs with metastatic potential. Moreover, the epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs) have also received increasing attention as important CTC markers owing to their roles in the biological progression of metastasis. In addition to these markers, researchers have attempted to develop detection or capture techniques for CTCs. Notably, however, the establishment of metastasis requires cancer-host interactions. Markers from host cells, such as macrophages, mesenchymal stem cells, and bone marrow-derived cells, which constitute the premetastatic niche, may become novel biomarkers for predicting relapse or metastasis or monitoring the effects of treatment. Biological studies of CTCs are still emerging. However, recent technical innovations, such as next-generation sequencing, are being used more commonly and could help to clarify the mechanism of metastasis. Additionally, biological findings are gradually being accumulated, adding to our body of knowledge on CTCs. In this review, we will summarize recent approaches to detect or capture CTCs. Moreover, we will introduce recent studies of the clinical and biological importance of CTCs and host cells.

Project description:Background and objectiveIn cancer patients, circulating tumor cells (CTCs) are employed as "Liquid Biopsy" for tumor detection, prognosis and assessment of the response to therapy. CTCs are responsible for tumor dissemination but the mechanisms involved in intravasation, survival in the circulation and extravasation at secondary sites to establish metastases are not fully characterized. In lung cancer patients, CTCs are present in very high numbers in small cell lung cancer (SCLC) that is found disseminated in most patients upon first presentation and has a dismal prognosis. This review aims at the discussion of recent work on metastatic SCLC and novel insights into the process of dissemination derived from the access to a panel of unique SCLC CTC lines.MethodsPubMed and Euro PMC were searched from January 1st, 2015 to September 23th, 2022 using the following key words: "SCLC", "NSCLC", "CTC" and "Angiogenesis" and supplemented by data from our own work.Key content and findingsExperimental and clinical data indicate that the intravasation of single, apoptotic or clustered CTCs occur via leaky neoangiogenetic vessels in the tumor core and not via crossing of the adjacent tumor stroma after EMT. Furthermore, in lung cancer only EpCAM-positive CTCs have been found to have prognostic impact. All our established SCLC CTC lines form spontaneously EpCAM-positive large and chemoresistant spheroids (tumorospheres) that may become trapped in microvessels in vivo and are suggested to extravasate by physical force. The rate-limiting step of the shedding of CTCs is most likely the presence of irregular and leaky tumor vessels or in case of SCLC, also via vessels formed by vasculogenic mimicry. Therefore, lower microvessel densities (MVD) in NSCLC can explain the relative rarity of CTCs in NSCLC versus SCLC.ConclusionsThe detection of CTCs lacks standardized techniques, is difficult in non-metastatic patients and important cell biological mechanisms of dissemination need still to be resolved, especially in respect to the actual metastasis-inducing cells. Expression of VEGF and the MVD are key prognostic indicators for tumors and ultimately, enumeration of CTCs seems to reflect neoangiogenetic vascular supply of tumors and prognosis.

Project description:BackgroundThe correlation between tumor markers (TM) and TNM stage of non-small-cell lung cancer (NSCLC) has not been widely reported.MethodsTM levels (CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, and SCC-Ag) in 424 cases of lung adenocarcinoma (LAC), 166 cases of lung squamous cell carcinoma (LSCC), and 103 cases of benign chest disease (BCD) were analyzed before treatment.ResultsBy Kendall's tau-b correlation analysis, CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, and SCC-Ag were correlated with T stage of LAC (r = 0.235, p < 0.05; r = 0.298, p < 0.05; r = 0.254, p < 0.05; r = 0.063, p < 0.05; r = 0.080, p < 0.05; r = 0.268, p < 0.05; and r = 0.080, p < 0.05). CEA, CA125, CA15-3, CA19-9, CA72-4, and CYFRA21-1 were correlated with N stage of LAC (r = 0.356, p < 0.05; r = 0.415, p < 0.05; r = 0.340, p < 0.05; r = 0.117, p < 0.05; r = 0.175, p < 0.05; and r = 0.351, p < 0.05). CEA, CA125, CA15-3, CA19-9, CA72-4, and CYFRA21-1 were correlated with M stage of LAC (r = 0.365, p < 0.05; r = 0.353, p < 0.05; r = 0.293, p < 0.05; r = 0.135, p < 0.05; r = 0.169, p < 0.05; and r = 0.312, p < 0.05). CA125, CYFRA21-1, and SCC-Ag were correlated with T stage of LSCC (r = 0.202, p < 0.05; r = 0.233, p < 0.05; and r = 0.099, p < 0.05). CA125 and CYFRA21-1 were correlated with N stage of LSCC (r = 0.178, p < 0.05 and r = 0.284, p < 0.05). CA125, CA15-3, and CYFRA21-1 were correlated with M stage of LSCC (r = 0.214, p < 0.05; r = 0.152, p < 0.05; and r = 0.213, p < 0.05). Combining hazard ratio, AUC, sensitivity, specificity, NPV, and PPV, it was concluded that CEA and CYFRA21-1were the most related TM of LAC. SCC-Ag and CYFRA21-1 were the most related TM of LSCC.ConclusionsCEA combined with CYFRA21-1 contributed to auxiliary diagnosis of LAC. CYFRA21-1 combined with SCC-Ag contributed to auxiliary diagnosis of LSCC. CEA, CA125, CA15-3, CA19-9, CA72-4, and CYFRA21-1 were correlated with primary tissue and metastasis of LAC. CA125 and CYFRA21-1 were correlated with primary tissue and metastasis of LSCC.

Dataset Information

Clinical significance of circulating tumor cells and tumor markers in the diagnosis of lung cancer.

Background

Methods

Results

Conclusions

Publications

Clinical significance of circulating tumor cells and tumor markers in the diagnosis of lung cancer.

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