Expression Of Pleiotrophin In Patients With Lung Cancer And Its Clinical Implications

Objective:To investigate the expression status of pleiotrophin (PTN) in human lung cancertissues and its correlation with clinicopathologic parameters of patients. To explore thevalue of PTN as a biomarker in diagnosis of lung cancer.Methods:Fresh lung cancer tissues and corresponding pericarcinous tissues (2-5cm beyond thecancer margin) and normal lung tissues (surgical resection specimens of tissue near the cutend) were collected from15patients confirmed with lung cancer undergoing surgicaloprations. The expression of PTN mRNA was detected by RT-PCR technique. Using tissuemicroarray and immunohistochemical techniques, the expression of PTN proteins wasdetected in92lung cancer tissues. Fifteen tissue samples from benign pulmonary lesionswere also analyzed as control subjects. The correlation between the expression of PTN inlung cancer tissues and the clinicopathological parameters of the patients were analyzed.Results:1. One550bp fragment was amplificated from PTN gene by semi-quantitative PCR.The expression of PTN mRNA in lung cancer tissues was significantly higher thancorresponding pericarcinous tissues (0.5052±0.0377vs0.1587±0.0425, P＜0.001) andnormal lung tissues (0.5052±0.0377vs0.0006±0.0001, P＜0.001).The expression ofPTN mRNA of pericarcinous tissues was significantly higher than normal lung tissues(0.1587±0.0425vs0.0006±0.0001, P＜0.001).2. Immunohistochemical staining showed that PTN protein in lung cancer tissues wasmainly located in cytoplasm and cytomembrane. The expression of PTN protein of lungcancer tissues was significantly higher than benign pulmonary lesion tissues(0.2134(0.0226-0.3737) vs0.0460(0-0.1943), P＜0.01).In addition, higher expression of PTN was observed in small cell lung cancer tissue compared with those from squamouscell carcinoma (0.2330(0.1919-0.3737) vs0.2134(0.0292-0.2977),P＜0.05) andadenocarcinoma (0.2330(0.1919-0.3737) vs0.2005(0.0226-0.2854),P＜0.05). Also, PTNprotein expression was upregulated in poorly differentiated lung cancer tissues than thosein well and moderate-differentiated tissue samples (0.2218(0.0444-0.3737) vs0.2067(0.0226-0.2854), P＜0.05). The expression of PTN protein in advanced lung cancer ofTNM stage Ⅲ-Ⅳ was significantly higher than those of stage Ⅰ-Ⅱ(0.2171(0.0444-0.2977) vs0.1939(0.0226-0.2632),P＜0.01).The PTN expression in lungcancer tissues was found to be closely correlated with TNM staging (2=6.097,P＜0.05),pathological type (2=8.013,P＜0.05) and differentiation degree (2=3.941,P＜0.05) incontrast to patient age, sex, smoking status, tumor size, lymph node metastasis and distantmetastasis(P＞0.05).Conclusion:1. The PTN mRNA and protein is highly expressed in cancerous tissue samples fromlung cancer patients, and is helpful in discriminating lung cancer from benign pulmonarylesions; PTN may become a novel biomarker for the diagnosis of lung cancer.2. PTN expression status in lung cancer tissues was correlated with pathological type.It was higher expressed in cancerous tissues from small cell lung cancer than those ofnon-small cell lung cancer, indicating that PTN may be more helpful in the diagnosis ofsmall cell lung cancer.3. PTN expression status in lung cancer tissues was also correlated with tumor TNMstaging and differentiation degree. Higher expression of PTN was observed in advancedand poorly differentiated lung cancer tissues, prompt PTN is closely related to theoccurrence and development of lung cancer.