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Introduction
As the world's second most common type of gynecological cancer, cervical cancer causes ~12,820 newly diagnosed cases and 4,210 mortalities each year in the United States (1). Although radical surgical treatment and radiotherapy are effective treatments, more than a third of these patients will develop progressive or recurrent tumors (2,3). Currently, the International Federation of Obstetricians and Gynecologists (FIGO) staging system, depth of invasion and lymph node (LN) status are recognized prognosis factors in patients with cervical cancer (4–6). Among these factors, the adverse impact of LN metastasis on patients with cervical cancer was confirmed in certain recent clinical studies (4,7). Currently, there are some studies that have investigated the mechanism of cervical LN metastasis (8,9); however, a there is still no valid biomarker for LN metastasis. Therefore, a comprehensive understanding of the pathways and genes contributing to the development and LN metastasis of cervical cancer is required.
The peroxisome proliferator-activated receptor (PPAR) signaling pathway was first reported in 1990, and demonstrated to be involved in glucose and lipid metabolism (10). With further investigation of the association between cell metabolism and cancer, the role of PPARs in tumors has been continuously explored. In general, deregulation of PPARγ, a subtype of PPARs, is detected in peripheral tissues associated with lipid metabolism (11), whereas Mandard and Patsouris (12) reported that PPARγ was also deregulated in inflammation and cancer. Although evidence has suggested that PPAR ligands may inhibit tumor angiogenesis during tumor formation (13,14), the importance of PPAR signaling pathway in tumors remains unclear, particularly the role in the carcinogenesis and metastasis of cervical cancer.
As members of the zinc-dependent protease family, matrix metalloproteinases (MMPs) are important factors involved in the degradation of extracellular matrix and proteolysis (15). As an interstitial collagenase, abnormal expression of MMP1 has been reported to be associated with progression of human cancer. The increased expression of MMP1 detected in prostate cancer (16), bladder cancer (17) and gastric cancer (18) has been demonstrated to be closely associated with prognosis. In addition, MMP1 has been reported to promote angiogenesis by activating the endothelial protease-activated receptor-1 (19). Anand et al (20) reported that glioma cell invasion can be promoted by MMP1 through the mitogen-activated protein kinase pathway (20). Whether MMP1 has a role in...