Signal transducer and activator of transcription 3 overexpression promotes lymph node micrometastasis in early-stage non-small cell lung cancer

Abstract

Background: Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in several malignancies. Here, we define the correlation between STAT3 expression and lymph node micrometastasis of early-stage non-small cell lung cancer. Then we highlight some possibilities associated with developing a way to detect tumor micrometastasis and an anticancer drug that might therapeutically inhibit the STAT3 signaling pathway.

Methods: The samples were collected from 50 patients with early-stage non-small cell lung cancer and 50 patients with benign lung tumors. Mucin 1 mRNA expression was evaluated to determine lymph node micrometastasis status. STAT3 mRNA, STAT3 protein, and phosphorylated STAT3 protein expression were evaluated through reverse transcription polymerase chain reaction, western blot, and immunohistochemistry, respectively. Measurement data was represented as mean ± standard deviation, and the t-rest or F-test were used. The χ² -test was used in enumeration data. Logistic regression analysis was carried out to determine the independent risk factors influencing lymph node micrometastasis.

Results: STAT3 mRNA and proteins expression were correlated with lymph node micrometastasis (P < 0.05). Logistic regression analysis revealed STAT3 protein overexpression and the differentiation degree of tumors were independent risk factors for lymph node micrometastasis.

Conclusion: Overexpression of STAT3 might promote lymphatic micrometastasis of early-stage non-small cell lung cancer and might be a clinical predictor of lymph node micrometastasis.

Keywords: Lymph node micrometastasis; mucin 1; non-small cell lung cancer; phosphorylated signal transducer and activator of transcription 3; signal transducer and activator of transcription 3.

Figure 1

Mucin 1 (MUC1) mRNA expression in lymph node samples. M, marker; 1: negative control lymph node sample; 2: lymph node sample without micrometastasis; 3~5: lymph node samples with micrometastasis.

Figure 2

Signal transducer and activator of transcription 3 (STAT3) mRNA expression in lung cancer samples and normal lung tissue samples. M, marker; 1~2: normal lung tissue samples; 3~4: non‐small cell lung cancer samples with lymph node micrometastasis; 5: non‐small cell lung cancer samples without lymph node micrometastasis.

Figure 3

Signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (pSTAT3) proteins expression in lung cancer samples and normal lung tissue samples. 1~2: normal lung tissue samples; 3~4: non‐small cell lung cancer samples with lymph node micrometastasis; 5: non‐small cell lung cancer samples without lymph node micrometastasis.

Figure 4

Signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (pSTAT3) proteins expression in lung cancer samples and normal lung tissue samples (streptavidin‐peroxidase method, ×200). (a) STAT3 positive expression in squamous cell lung cancer, (b) STAT3 positive expression in lung adenocarcinoma, (c) STAT3 negative expression in squamous cell lung cancer, (d) STAT3 negative expression in lung adenocarcinoma, (e) STAT3 negative expression in normal lung tissue, (f) pSTAT3 positive expression in squamous cell lung cancer, (g) pSTAT3 positive expression in lung adenocarcinoma, (h) pSTAT3 negative expression in squamous cell lung cancer, (i) pSTAT3 negative expression in lung adenocarcinoma, and (j) pSTAT3 negative expression in normal lung tissue.