The cervical cancer was the predominant cancer among women and the global burden of cervical cancer is disproportionately high among the developing countries [13]. It is known that the infection of human papilloma (HPV) virus, especially the high risk type HPV virus, is the main cause of cervical cancer [14, 15]. The accurate bio-markers are meaningful for the prediction of the prognosis in cervical cancer.
In recent decades, molecular markers have been identified playing important role in the detection and treatment of patients with several different cancer types, including cervical cancer [16–21]. Yang et al. indicated that high Delta-like ligand 4 (DLL4) expression predicts pelvic lymph node metastasis and poor survival in cervical cancer that may be a potential clinical diagnostic marker for patients with early-stage cervical cancer [18]. Yang L et al. investigated that MALAT1 might be an important marker of prognosis and a potential therapeutic target of cervical cancer. Zhang et al. also demonstrated that MALAT-1 is upregulated and played an indispensible role in cervical cancer, which may act as a potential prognostic indicator for cervical cancer [17, 20]. Ling S et al. found miR-206 significantly downregulated in cervical cancer samples than adjacent normal tissues that may act as a novel diagnostic and prognostic marker [21].
The dysexpression of HOX genes have recently been reported in various human cancers. HOXA9, a HOX gene, has also been implicated in human diseases, including cancers, such as ovarian cancer, glioblastoma, lung cancer, breast cancer and so on [12, 22–26]. Song Yi Ko et al. found that high HOXA9 expression in clinical specimens of ovarian cancer was strongly associated with increased abundance of tumor-associated macrophages (TAMs) and intratumoral T-regulatory cells [22]. Céline S. Gonçalves et al. as well as Marta Pojo et al. identifed HOXA9 as a critical oncogene in the initiation and progression of glioma that establish HOXA9 as a driver of glioma initiation, aggressiveness and resistance to therapy [23, 24]. John Wrangle et al. defined a three-gene panel, CDO1, HOXA9, and TAC1, which degree of sensitivity and specificity may be of high value to diagnose the earliest stages of NSCLC [25]. Sun et al. implicate the HMGA2–TET1–HOX signaling pathway in the epigenetic regulation of human breast cancer and that stratifies breast patient survival [26].
In the present study, we have studied HOXA9 mRNA expression in 154 specimens of cervical cancer patients by qRT-PCR, which can quantify mRNA levels with high accuracy, and found that HOXA9 mRNA was down-expressed in the majority of cervical cancer tissues compared with normal tissues. The down-regulated HOXA9 result indicated that it may therefore function as a tumor suppressor. Then we further analyzed the association between HOXA9 expression and clinical characteristics of the patients with cervical cancer. The results indicated that the expression of HOXA9 was tightly correlated with TNM stage, pathological grade, FIGO stage and differentiation, which showed that HOXA9 participated in the development and progression of cervical cancer. The Kaplan–Meier analysis showed that patients with a high HOXA9 expression had a longer overall survival compared to those with low expression (log rank test, P < 0.05), revealing HOXA9 was related to the prognosis of cervical cancer. According to cox regression analysis, low expression of HOXA9 was confirmed to be related to the prognosis of cervical caner and it could be an independent prognostic indicator and provided a promising therapeutic strategy for cervical cancer.