Prognostic value of cytokeratin-7 mRNA expression in peripheral whole blood of advanced lung adenocarcinoma patients

Koren, Ana; Sodja, Eva; Rijavec, Matija; Jež, Mojca; Kovač, Viljem; Korošec, Peter; Čufer, Tanja

doi:10.1007/s13402-015-0238-4

Cited by 16 publications

(15 citation statements)

References 53 publications

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“…Since metastasis is one of the most crucial factors determining the survival of cancer patients, ample attempts have been made to identify key molecular mediators that control metastasis. Nonsmall cell lung cancer (NSCLC) is a highly metastatic malignancy, and the disease is estimated to be the leading cause of cancer-related death [4][5][6][7][8]. The endogenous gas nitric oxide (NO) is known to play a role in the progression of different types of cancer [9] and it has been found that the expression of several forms of NO synthases (NOSs) is strongly upregulated in, among others, NSCLC cells [10].…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide increases the migratory activity of non-small cell lung cancer cells via AKT-mediated integrin αv and β1 upregulation

2016

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Background Previously, nitric oxide (NO) has been found to affect the metastatic behavior of various types of cancer. In addition, it has been found that alterations in integrin expression may have profound effects on cancer cell survival and migration. Here, we aimed at assessing the effects of non-toxic concentrations of NO on human non-small cell lung cancer (NSCLC) cells, including the expression of integrins and the migration of these cells. Methods The cytotoxic and proliferative effects of NO on human NSCLC-derived H460, H292 and H23 cells were tested by MTT assay. The migration capacities of these cells was evaluated by wound healing and transwell migration assays. The expression of integrins and migration-associated proteins was determined by Western blot analyses. Results We found that NO treatment caused a significant increase in the expression of integrin αv and β1 in all three NSCLC-derived cell lines tested. Known migrationassociated proteins acting downstream of these integrins, including focal adhesion kinase (FAK), active RhoA (Rho-GTP) and active cell division control 42 (Cdc42-GTP), were found to be significantly activated in response to NO. In addition, we found that NO-treated cells showed an increased motility and that this motility was associated with a significant increase in the number of filopodia per cell. We also found that NO-treated cells exhibited increased active protein kinase G (PKG), protein kinase B (AKT) and FAK expression levels. Using a pharmacological approach, we found that the integrinmodulating effect of NO is most likely brought about by a PKG/AKT-dependent mechanism, since the observed changes in integrin expression were abolished by AKT inhibitors, but not by FAK inhibitors. Conclusion Our data suggest a novel role of NO in the regulation of integrin expression and, concomitantly, the migratory capacity of NSCLC cells.

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Section: Introductionmentioning

confidence: 99%

Nitric oxide increases the migratory activity of non-small cell lung cancer cells via AKT-mediated integrin αv and β1 upregulation

2016

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“…In that study, however, they took 20 mL of blood from 43 patients with NSCLC at various stages of disease (56% stage IV) using, after the negative selection, immunofluorescence, a method with a poor sensitivity. In another study in NSCLC patients, CTCs were highlighted by CK7 mRNA expression measured by RT-PCR; there was not a significant association between CK7 mRNA levels and the response to chemotherapy or the survival [ 45 ]. Based on our data, we think this contrasting result is due to the use of only one epithelial marker and so it emphasizes how the expression of mesenchymal markers in combination with epithelial ones can significantly improve the CTCs detection.…”

Section: Discussionmentioning

confidence: 99%

Molecular Detection of EMT Markers in Circulating Tumor Cells from Metastatic Non-Small Cell Lung Cancer Patients: Potential Role in Clinical Practice

Milano

Mazzetta

Valente

et al. 2018

Analytical Cellular Pathology

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Background Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related mortality; nevertheless, there are few data regarding detection of circulating tumor cells (CTCs) in NSCLC, compared to other kinds of cancers in which their prognostic roles have already been defined. This difference is likely due to detection methods based on the epithelial marker expression which ignore CTCs undergoing epithelial-mesenchymal transition (CTCsEMT). Methods After optimization of the test with spiking experiments of A549 cells undergoing TGF-β1-induced EMT (A549EMT), the CTCsEMT were enriched by immunomagnetic depletion of leukocytes and then characterized by a RT-PCR assay based on the retrieval of epithelial and EMT-related genes. Blood samples from ten metastatic NSCLC patients before starting treatment and during chemotherapy were used to test this approach by longitudinal monitoring. Ten age- and sex-matched healthy subjects were also enrolled as controls. Results Recovery experiments of spiked A549EMT cells showed that the RT-PCR assay is a reliable method for detection of CTCsEMT. CTCsEMT were detected in three patients at baseline and in six patients after four cycles of cysplatin-based chemotherapy. Longitudinal monitoring of three patients showed that the CTCsEMT detection is related to poor therapeutic response. Conclusions The RT-PCR-based approach for the evaluation of CTCsEMT phenotype could be a promising and inexpensive tool to predict the prognosis and the therapeutic response in NSCLC patients.

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“…Total RNA from tumor and normal tissue samples was extracted using a miRNeasy Mini Kit (Qiagen) according to the manufacturer's instructions. RNA from peripheral whole blood samples was extracted using a PAXgene Blood miRNA Kit (PreAnalytiX) as previously described [ 48 ]. Briefly, all RNA samples were treated with RNase-free DNase (Qiagen) and reverse transcribed to cDNA using high-capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

HighBMI1mRNA expression in peripheral whole blood is associated with favorable prognosis in advanced non-small cell lung cancer patients

et al. 2017

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Polycomb group member protein BMI1 is involved in maintaining cell identity, proliferation, differentiation and human oncogenesis. In the present study, we determined BMI1 mRNA expression in whole blood and evaluated the impact of the expression level on the treatment response and survival of 96 advanced NSCLC patients treated with first-line platinum-based chemotherapy. We also determined BMI1 mRNA expression in primary tumors from 22 operable NSCLC patients treated with radical surgery. We found that compared with control subjects, BMI1 mRNA expression in whole blood of advanced NSCLC patients was decreased (P<0.001). Similarly, we observed decreased BMI1 mRNA expression in primary tumors compared to normal lungs from operable NSCLC patients (P=0.001). We found high BMI1 mRNA expression in blood was associated with longer progression-free survival (PFS) (P=0.049) and overall survival (OS) (P=0.012) in advanced NSCLC patients treated with first-line platinum-based chemotherapy. However, no association between the BMI1 mRNA level and response to chemotherapy was found (P=0.21). Multivariate Cox proportional hazards regression analysis showed elevated BMI1 mRNA level in whole blood was an independent prognostic factor for longer PFS (P=0.012) and OS (P<0.001). In conclusion, BMI1 mRNA expression in whole blood might represent a new biomarker for the diagnosis and prognosis of NSCLC.

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Prognostic value of cytokeratin-7 mRNA expression in peripheral whole blood of advanced lung adenocarcinoma patients

Cited by 16 publications

References 53 publications

Nitric oxide increases the migratory activity of non-small cell lung cancer cells via AKT-mediated integrin αv and β1 upregulation

Nitric oxide increases the migratory activity of non-small cell lung cancer cells via AKT-mediated integrin αv and β1 upregulation

Molecular Detection of EMT Markers in Circulating Tumor Cells from Metastatic Non-Small Cell Lung Cancer Patients: Potential Role in Clinical Practice

HighBMI1mRNA expression in peripheral whole blood is associated with favorable prognosis in advanced non-small cell lung cancer patients

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