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Published on: December 4, 2018
Expression and unique functions of four nuclear factor of activated T cells isoforms in non-small cell lung cancer
Zhao-Li Chen1, Shou-Hua Zhao, Zhen Wang
1Department of Thoracic Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, PR China.
Abstract:
Nuclear factor of activated T cells (NFAT) is an important family of transcription factors that can be activated by calmodulin and calcineurin in human cells. To investigate the expression and clinical significance of NFAT isoforms and calcineurin in non-small cell lung cancer (NSCLC), we collected tumor and adjacent normal tissues from 159 NSCLC patients and assembled them in a tissue microarray. Protein levels of NFAT1, NFAT2, NFAT3, NFAT4, and calcineurin were determined using immunohistochemistry. Correlations between NFAT and calcineurin expression and clinicopathologic characteristics were analyzed. We found that the positive rates of NFAT1 (52.8%, 84/159), NFAT2 (11.3%, 18/159), NFAT3 (28.3%, 45/159), NFAT4 (47.2%, 75/159), and calcineurin (47.8%, 76/159) expression were significantly higher in tumor tissues than in adjacent normal lung tissues (P<0.001), respectively. The positive rate of NFAT1 expression was significantly higher in patients with adenocarcinoma (63.5%, 47/74) than in those with squamous cell carcinoma (43.5%, 37/85) (χ2=6.340, P=0.012); with lymph node metastasis (61.6%, 53/86) than without lymph node metastasis (42.5%, 31/73) (χ2=5.818, P=0.016); and with stage-II and -III diseases (61.8%, 55/89) than with stage-I disease (41.4%, 29/70) (χ2=6.524, P=0.011). Moreover, the overexpression of NFAT1 was associated with poor survival of NSCLC patients (χ2=5.006, P=0.025). The positive rate of NFAT4 was significantly higher in patients with squamous carcinoma (57.6%, 49/85) than in those with adenocarcinoma (35.1%, 26/74) (χ2=8.045, P=0.005) and with high and moderate differentiation (54.9%, 61/111) than with low differentiation (29.2%, 14/48) (χ2=8.943, P=0.003). Calcineurin overexpression was significantly associated with histologic type (higher in squamous carcinoma than in adenocarcinoma, χ2=8.897, P=0.003), differentiation grade (higher in high-moderation grade than in low grade, χ2=9.566, P=0.002) and gender (higher in male than in female, χ2=5.766, P=0.016). Furthermore, calcineurin expression was significantly correlated with NFAT4 level (r=0.429, P<0.001). These results suggest that NFAT1 expression is associated with lung adenocarcinoma progression, and NFAT4 expression, which was higher in squamous lung cancer, is associated with calcineurin expression and differentiation grade.
Insights
Nuclear factor of activated T cells (NFAT) and calcineurin are upregulated in non-small cell lung cancer (NSCLC). NFAT1 overexpression correlates with poorer survival in NSCLC patients, while NFAT4 and calcineurin expression are linked to specific subtypes and differentiation.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Nuclear factor of activated T cells (NFAT) are transcription factors crucial for cellular processes.
- Calcineurin is a key regulator of NFAT activation in human cells.
- The role of NFAT isoforms and calcineurin in non-small cell lung cancer (NSCLC) remains to be fully elucidated.
Purpose of the Study:
- To investigate the expression levels of NFAT1, NFAT2, NFAT3, NFAT4, and calcineurin in NSCLC tissues.
- To analyze the correlation between the expression of these proteins and clinicopathological characteristics of NSCLC patients.
- To determine the prognostic significance of NFAT and calcineurin expression in NSCLC.
Main Methods:
- Tumor and adjacent normal tissues from 159 NSCLC patients were collected for tissue microarray construction.
- Immunohistochemistry was employed to assess the protein levels of NFAT1, NFAT2, NFAT3, NFAT4, and calcineurin.
- Statistical analyses, including chi-squared tests and correlation analysis, were performed to evaluate expression patterns and clinical associations.
Main Results:
- NFAT1, NFAT2, NFAT3, NFAT4, and calcineurin showed significantly higher expression in NSCLC tumor tissues compared to normal tissues.
- NFAT1 overexpression was associated with adenocarcinoma, lymph node metastasis, advanced stage (II-III), and poorer patient survival.
- NFAT4 and calcineurin expression were significantly higher in squamous cell carcinoma and associated with differentiation grade, with calcineurin also linked to gender.
Conclusions:
- NFAT1 expression is implicated in the progression of lung adenocarcinoma and serves as a potential prognostic marker.
- NFAT4 and calcineurin are differentially expressed in NSCLC subtypes and are associated with tumor differentiation, suggesting their involvement in specific lung cancer pathobiology.
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