Expression of Periostin, Homologous with an Insect Cell Adhesion Molecule, as a Prognostic Marker in Non‐small Cell Lung Cancers

Abstract

We used our palindromic polymerase chain reaction (PCR)-driven cDNA differential display technique to identify and isolate a gene, designated periostin, from cancer tissues and found it to be overexpressed in several human tumors. We attempted to determine the influence of periostin expression on clinical outcome in patients with non-small cell lung cancer (NSCLC) by reverse transcriptase (RT)-PCR analysis. Periostin gene was highly expressed at the tumor periphery of lung cancer tissue but not within the tumor by in situ RNA hybridization, suggesting that expression of periostin may be involved in the process of tumor invasion. Periostin transcripts were detected in 50 (49.0%) of the tumor samples, although some paired normal lung samples showed weak expression. There was no relationship between periostin gene expression and gender, N-or Tstatus. The NSCLC patients with periostin expression had significantly poorer survival than the patients without periostin expression (P = = = =0.0338). Key words: Periostin-RT-PCR-Lung cancer-PrognosisLung cancer is a major cause of death from malignant diseases, due to its high incidence and malignant behavior, and the lack of major advances in treatment strategy. 1)Lung cancer was the leading indication for respiratory surgery (42.2%) in 1998 in Japan, with more than 15 000 patients undergoing surgical operation at Japanese institutions.2) The clinical behavior of non-small lung cancer (NSCLC) is largely associated with its stage.3) However, a significant number of tumors in patients with early-stage NSCLC show aggressive behavior and a tendency to relapse. Moreover, the prognosis for patients with operable NSCLC remains gloomy in comparison with that observed in operable gastric, colon, or breast cancer.4) A variety of clinicopathologic characteristics may affect prognosis. 5)Despite steadily accumulating evidence that numerous genetic markers influence the biological behavior of NSCLC, the intrinsic nature of the gene deregulation that leads small tumors to metastasize remains highly elusive. 6)The abnormal expression of certain genes in cancer cells is closely related to various aspects of tumor progression, including tumor growth, invasion and metastasis. Recently, we used the palindromic polymerase chain reaction (PCR)-driven cDNA differential display technique developed in our laboratory 7) to identify and isolate periostin cDNA, and found it to be overexpressed in several human tumors including primary colon cancer, metastatic liver cancer from colon cancer and breast cancer (Bao et al., manuscript in preparation). The periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule.8-10) It was reported that cellular adhesion molecules play an important role in the process of metastasis. 11)As available prognostic markers leave much to be desired for NSCLC, we investigated periostin transcript in patients with NSCLC by means of a reverse transcriptase PCR (RT-PCR) and in situ hybridization analysis, and we assessed t...

Periostin is frequently overexpressed and enhances invasion and angiogenesis in oral cancer

“…Periostin is originally identified from osteoblasts and functions as a cell adhesion molecule for preosteoblast and to participate in osteoblast recruitment, attachment and spreading (Takeshita et al, 1993;Horiuchi et al, 1999). Previous studies showed that the expression of Periostin is upregulated in various types of cancer, including head and neck (Gonzalez et al, 2003), colon , Tai et al, 2005, breast , lung (Sasaki et al, 2001c) and ovarian cancer (Gillan et al, 2002). Here, we also found that 68% of OSCC cases expressed Periostin mRNA and 69% of OSCC cases expressed Periostin protein.…”

Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

“…Previous studies showed that periostin was up-regulated in various types of cancers such as the lung, 26 brain, 8 ovary, 9 breast, 27 colon 11 and oral cavity, 28,29 and its serum level was reported to be high in patients with thymoma, 30 non-small cell lung cancer 10 and breast cancer. 31 These reports suggested that periostin is involved in tumor spread, invasion and metastasis.…”

“…6,7 Recently, the expression of periostin has been implicated in the development of variety of carcinomas such as neuroblastoma, 8 epithelial ovarian cancer 9 and non-small cell lung carcinoma. 10 Periostin has been also reported to promote the metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway. 11 In addition, periostin has been suggested to promote the invasiveness or growth rate and confer resistance to hypoxia in pancreatic cancer cells, although the source of this protein was stromal cells rather than cancer cells.…”

Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the β4 integrin and the PI3k pathway

“…A similar structure was reported for fasciclin I, a cell adhesion molecule involved in the development of the central nervous system of insects (Zinn et al, 1988), and for the big-h3 molecule, a secreted protein induced by TGF-b1 which promotes the attachment and spreading of fibroblasts (Skonier et al, 1992;LeBaron et al, 1995). Periostin was found to be overexpressed in various types of human cancer such as lung (Sasaki et al, 2001a), brain (Sasaki et al, 2002), ovary (Gillan et al, 2002), breast (Shao et al, 2004) and colon cancers Tai et al, 2005) and elevated levels have been detected in sera of patients with thymoma (Sasaki et al, 2001b), non-small lung carcinoma (Sasaki et al, 2001c) and breast cancer (Sasaki et al, 2003). Although these reports implicate periostin in tumour spread, the functional role of this protein is poorly described and recent publications report conflicting data.…”