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Clinical value of MLH1-negative circulating tumor cells in lung cancer patients.

ABSTRACT: Circulating tumor cells (CTCs) serve as valuable biomarkers. However, MutL homolog 1 (MLH1)-negative CTCs and their clinical significance in lung cancer are nearly unknown.Here, bioinformatic analysis of MLH1 expression and its clinical significance was conducted using the Oncomine, Ualcan, and Kaplan-Meier plotter websites. Size-based isolation and RNA in situ hybridization assays were used to identify CTCs and evaluate MLH1 and mesenchymal marker expression in CTCs. MLH1 was downregulated in lung cancer patients. Patients with lower MLH1 expression levels had worse prognoses. In a cohort of 32 randomly selected patients with lung cancer, the patients with poorer treatment responses had more MLH1-negative CTCs. The total CTCs, MLH1-negative CTCs and mesenchymal markers-expressing CTCs levels were negatively correlated with prognosis in the lung cancer patients.Our data showed the clinical significance of MLH1 expression in lung cancer tissues. The characterization and numeration of CTCs based on the expression of MLH1 and mesenchymal markers may be a convenient approach for predicting treatment response and prognosis in lung cancer.

SUBMITTER: Liang JY

PROVIDER: S-EPMC6636948 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Clinical value of MLH1-negative circulating tumor cells in lung cancer patients.

Liang Jin-Yan JY Yang Qi-Fan QF Zeng Yu-Lan YL Liu Yang-Yang YY Liu Yu-Ting YT Gu Fei-Fei FF Hu Yue Y Zhang Kai K Zhong Hao H Liu Li L

Medicine 20190601 25

Circulating tumor cells (CTCs) serve as valuable biomarkers. However, MutL homolog 1 (MLH1)-negative CTCs and their clinical significance in lung cancer are nearly unknown.Here, bioinformatic analysis of MLH1 expression and its clinical significance was conducted using the Oncomine, Ualcan, and Kaplan-Meier plotter websites. Size-based isolation and RNA in situ hybridization assays were used to identify CTCs and evaluate MLH1 and mesenchymal marker expression in CTCs. MLH1 was downregulated in l ...[more]

PMID: 31232917

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Project description:BackgroundAs one of the most aggressive gastrointestinal tract cancers, esophageal carcinoma (EC) had the tenth morbidity and sixth mortality rate globally in 2020. This study was conducted to investigate whether circulating tumor cells (CTCs) could be used as diagnostic and prognostic tools for patients with EC.MethodsPeripheral blood samples were collected from 129 patients newly diagnosed with EC, 17 individuals with benign diseases, and 75 healthy donors for CTC analysis using the negative enrichment-fluorescence in situ hybridization (NE-FISH) approach. The relationship between CTCs (counts and karyotypes) and clinicopathological features was then investigated. Moreover, overall survival (OS) and progression-free survival (PFS) were analyzed to evaluate the predictive value of CTCs.ResultsThe detection of CTCs using the NE-FISH approach helped in differentiating patients with EC from benign or healthy controls at a threshold of 2 per 3.2 ml peripheral blood with a sensitivity and specificity of 70.54% and 96.74%, respectively (area under the curve = 0.826, 95% CI 0.770-0.874, p < 0.001). The CTC count was associated with tumor depth (p = 0.012), but there was no correlation with other clinicopathological characteristics. Furthermore, the proportion of CTCs with chromosome 7 triploidy was linked to distant metastasis (p = 0.033) and TNM stage (p = 0.002). The OS was significantly shorter for patients with CTCs ≥ 3 than for those with CTCs < 3. Univariate analysis revealed that sex, vascular invasion, distant metastasis, tumor depth, lymph node metastasis, and TNM stage were the significant prognostic factors for patients with EC. Multivariate analysis demonstrated that distant metastasis (hazard ratio (HR) 3.262, 95% CI 1.671-6.369, p = 0.001 for PFS; HR 3.759, 95% CI 1.867-7.571, p < 0.001 for OS) was a significant prognostic factor for patients with EC.ConclusionsDetection of CTCs using NE-FISH could be helpful in the diagnosis of EC. The proportion of CTCs with chromosome 7 triploidy was related to distant metastasis and TNM stage. Patients with CTCs ≥ 3 had short OS, while distant metastasis was an independent factor indicating a poor prognosis for patients with EC.

Dataset Information

Clinical value of MLH1-negative circulating tumor cells in lung cancer patients.

Publications

Clinical value of MLH1-negative circulating tumor cells in lung cancer patients.

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