Overexpression of periostin predicts poor prognosis in non-small cell lung cancer

Abstract

The periostin protein, encoded by the POSTN gene, is a component of the extracellular matrix, which is expressed by fibroblasts and has been observed in a variety of human malignancies. The present study aimed to detect the expression of periostin in the tissues of non-small cell lung cancer (NSCLC) patients and benign lung tumors, and to correlate the results with the clinicopathological data of the subjects, in order to evaluate periostin as a potential prognostic marker. In total, 49 NSCLC patients and 6 benign lung tumors were included in this study. The protein level of periostin was detected in paired normal/paratumor/cancer tissues by a western blot analysis and the mRNA level in paired normal/cancer tissues was detected by quantitative polymerase chain reaction (qPCR). The results were then correlated with established biological and prognostic factors. Immunohistochemistry was used to confirm the location of periostin in the NSCLC tissues. Uni- and multivariate analyses were performed using Cox's proportional hazards regression model. The protein level of periostin was elevated in the cancer tissue of the NSCLC patients compared with the normal (P=0.017) and paratumor (P=0.000) tissues. The expression level in the male patients was much higher than in the female patients at the protein (P=0.001) and mRNA (P=0.010) levels. The mRNA level in the non-adenocarcinoma (non-ADC) patients was much higher than in the adenocarcinoma (ADC) patients (P=0.029). Periostin was demonstrated higher expression at the protein level in the pseudotumors and tuberculosis patients than in the adjacent (P=0.016) and surrounding tissues (P=0.001). Immunostaining indicated that high levels of periostin were present in the mesenchymal areas, but not in the cancer cells themselves. The patients with tumors exhibiting high-level periostin expression showed a significantly shorter survival time (P=0.036, log-rank test). The 3-year survival rate was 81.5% for patients with low-level periostin expression (periostin-L; n=27) and 45.4% for patients with high-level periostin expression (periostin-H; n=22). Similarly, pathological node (pN) status was a significant prognostic marker in the univariate Cox survival analysis. Notably, periostin-H expression was also identified as an independent prognostic factor by the multivariate analysis (P=0.011). These results showed that the overexpression of periostin predicts a poor prognosis, therefore it may be regarded as a novel molecule in the progression and development of NSCLC. The results provide an additional target for the adjuvant treatment of NSCLC.

Keywords: non-small cell lung cancer; overexpressed; periostin; prognostic factor.

Figure 1

Representative results of periostin protein expression in different lung tissues. Lane C, cancer tissue; lane P, paratumor tissue; lane N, normal tissue. Samples: S1, S2 and S3. kDa, molecular weight.

Figure 2

The protein level of periostin in different lung tissues. Lane C, cancer tissue; lane P, paratumor tissue; lane N, normal tissue. The periostin protein gray scale levels of cancer tissues, paratumor tissues and normal tissues were 1.810±0.415, 0.857±0.130 and 0.808±0.100, respectively.

Figure 3

Expression of periostin in non-small cell lung cancer (NSCLC) by immunohistochemistry. (A) Highly-stained squamous carcinoma. (B) Weakly-stained squamous carcinoma. (C) No staining of squamous carcinoma. (D) Highly-stained ADC. (E) Weakly-stained ADC. (F) No staining of ADC. ADC, adenocarcinoma. (Mayer’s hematoxylin stain; magnification, ×200).

Figure 4

Kaplan-Meier analysis of tumor-specific survival in all non-small cell lung cancer (NSCLC) patients according to periostin expression level. The 3-year survival rate was 81.5% for patients with low-level periostin expression (periostin-L; n=27), and 45.4% for patients with high-level periostin expression (periostin-H; n=22).