In recent years, molecular biomarkers for metastasis have been indentified in various cancers. Because biomarkers can be analyzed in a noninvasive and economic way, it is worth to find out more potential biomarkers for early diagnosis and prognosis of pancreatic cancer. Recent studies have shown that deregulation of oncogenes, tumor suppressor and genome maintenance genes, up-regulation of growth factors/growth factor receptor signaling cascade systems, and aberrant expression of apoptosis-regulating genes play crucial roles in the process of metastasis.
We performed this study to verify whether the high-expression of c-Myc in pancreatic tumor tissue may give rise to a high rate of LNM and PNI or not. Our study showed that the expression level of c-Myc was higher in cancer tissues than paracancerous tissues, and cytoplasm expression of c-Myc was significantly positive correlation with PNI (P
= 0.002). The result suggested that the over-expression of c-Myc played an important role in the process of pancreatic tumorigenesis and invasion. Furthermore, cytoplasm expression of c-Myc in cancer tissue acted as an independent risk factor for PNI (P
= 0.022). Therefore, c-Myc may be considered as a useful marker for metastasis and prognosis of pancreatic cancer. The precise mechanism of the c-Myc in tumorigenesis and invasion has remained elusive. The proto-oncogene c-Myc belongs to the family of myc genes and encodes a transcription factor that regulates cell proliferation, growth and apoptosis. Dysregulated expression of c-Myc found in various human tumors including lung cancer [17
], breast cancer [19
], colon cancer [17
], prostate cancer [20
], liver cancer [21
] and pancreatic cancer [22
], and is often associated with poor prognosis [23
]. The basic result showed that the effects of c-Myc on tumorigenesis have been mainly attributed to its ability to coordinate gene transcription [24
In addition, c-Myc acted as a downstream transcriptional effector of many signaling pathways involved in pancreatic carcinogenesis. It was regulated at multiple levels and its overexpression contributed to the genesis of cancer [25
]. For example Malte et al [26
] demonstrated that ectopic activation of NFATc1 and the Ca2+
/calcineurin signaling pathway was an important mechanism of oncogenic c-Myc activation in pancreatic cancer. However, so far only few research on the PNI, LNM and poor prognosis value of c-Myc over-expression have reported in pancreatic cancer. To the best knowledge, this was the first study to demonstrate overexpression of c-Myc was significantly positive correlation with PNI in pancreatic cancer. However, our study demonstrated that no significant association was observed between LNM and the expression level of c-Myc (P
> 0.05), which was consistent with some previous studies [9
]. These results indicated that different mechanisms may be involved in the pathogenesis of LNM and PIN.
Furthermore, our results showed that there was significant difference in the expression of Fas between cancer tissues and paracancerous tissues (P
< 0.0001). Analysis showed that Fas was lower in cancer tissues than paracancerous tissues. The results in current study suggested that Fas played an important role in the development of pancreatic cancer. According to the biology behavior and function of Fas, The pathogenesis of cancer might be associated with the abnormal regulation of apoptosis of Fas. We all known that Fas was best known for its ability to induce apoptosis but can also promote tumorigenesis in apoptosis-resistant tumor cells [27
]. Down-regulation of Fas expression in pancreatic cancer cells may be sufficient to confer resistance to Fas mediated apoptosis. Tang et al [28
] reported that Fas up-regulated mediator of apoptosis promote tumorigenesis. However, in one study, the results suggested that pancreatic cancer cells were resistant to Fas-mediated apoptosis by mechanisms excluding receptor down-regulation or Fas-associated phosphatase up-regulation and raise the possibility that Fasmediated apoptosis may be dependent on the activation of the JNK/p38 MAPK pathway in these cells. In addition, Bernstorff et al [13
] reported that loss of Fas expression in pancreatic adenocarcinoma significantly correlated with extrapancreatic spread of the tumors and was associated with a shorter overall survival.
Recently, a transcriptional analysis of perineural invasive PDAC cell lines has resulted in an extensive list of putative genes involved in perineural infiltration [29
]. A series of studies found that Fas can activate a number of non-apoptotic pathways that stimulate invasion [30
]. The present study showed that cytoplasm expression level of Fas in cancer tissues was negatively correlated with PNI (P
= 0.033). Taken together, Fas may be also considered as a potential marker for PNI and prognosis of cancer. Currently, there were few studies reported on the association between the expression of Fas and the PNI. Therefore, our result in this study could promote to understand the molecular mechanism of PNI. However, in this study, the statistically analysis showed that there was no significant association between LNM and expression level of Fas (P
> 0.05). The result was not consistent with a previous finding that significant association was observed between expression level of Fas and LNM (P
< 0.0001 ) [33
]. It may be partly due to small sample size involved in this study. Therefore, further studies will be necessary to determine whether Fas is a useful predictive factor for metastasis of pancreatic cancer.