Clinical Research Papers:

High temperature requirement A3 (HTRA3) expression predicts postoperative recurrence and survival in patients with non-small-cell lung cancer

Jingya Zhao, Jing Zhang, Xin Zhang, Mingxiang Feng and Jieming Qu _

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Oncotarget. 2016; 7:40725-40734. https://doi.org/10.18632/oncotarget.9173

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Jingya Zhao1,*, Jing Zhang2,*, Xin Zhang2, Mingxiang Feng3 and Jieming Qu4,1

1 Department of Pulmonary Medicine, Huadong Hospital, Fudan University, Shanghai, China

2 Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China

3 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

4 Department of Pulmonary Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

* These authors have contributed equally to this study

Correspondence to:

Jieming Qu, email:

Mingxiang Feng, email:

Keywords: HTRA3, postoperative recurrence, non-small-cell lung cancer, invasion, immunohistochemistry

Received: December 09, 2015 Accepted: April 16, 2016 Published: May 04, 2016


Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and its recurrence rate after complete resection is high, owing to local or distant metastases. Low expression of high temperature requirement A3 (HTRA3) has been reported to promote tumorigenesis, diminish the effects of anti-tumor treatments, and correlate with a malignant phenotype. To assess the involvement of HTRA3 in the prognosis of postoperative NSCLC, we obtained tumors from 78 patients who had undergone complete surgical resection, and immunohistochemically examined them for HTRA3 expression. HTRA3 was significantly down-regulated in lung cancer tissues compared with normal lung tissues, and only six tumor cases(7.7%) exhibited relatively high levels of HTRA3 (P < 0.001). Notably, high-HTRA3 patients were at significantly lower risk of postoperative recurrence than low-HTRA3 or HTRA3-negative patients (0% versus 31.2% and 35.0%; P = 0.044, 0.029, respectively). High expression of HTRA3 also independently indicated longer disease-free survival in Cox regression analysis (hazard ratio 0.39, 95%CI 0.16-0.95, P = 0.038). Ectopic expression of the long isoform of HTRA3 attenuated the invasion of an NSCLC cell line in a Transwell assay, while knockdown of HTRA3 had the converse effect. Thus, HTRA3 suppresses tumor cell invasiveness and may serve as a prognostic biomarker for postoperative recurrence or survival in NSCLC.

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