Abstract. Sensitive and specific biomarkers for the early detection of cervical cancer are urgently required to reduce the high morbidity and mortality of this disease. We previously demonstrated that circulating microRNAs (miRNAs) are correlated with certain types of human cancer. The aim of this study was to investigate the altered profile of serum miRNAs in cervical cancer patients in order to predict cervical cancer at a relative early stage. Serum samples were collected from 213 cervical cancer patients and 158 age-and ethnicity-matched controls. An initial screening of miRNA expression was performed by Solexa sequencing. Differential expression was validated using the stem-loop miRNA quantitative polymerase chain reaction (qPCR) assay in individual samples and the samples were arranged by two-phase selection and validation. The Solexa sequencing results revealed 12 markedly upregulated serum miRNAs in cervical cancer patients compared with controls. The reverse transcription-qPCR analysis identified a profile of 5 serum miRNAs (miR-21, -29a, -25, -200a and -486-5p) as a cervical cancer biomarker. The receiver operating characteristic curves indicated that a panel of 5 miRNAs constitutes a more sensitive and specific diagnostic test compared with any single miRNA-based assay, the squamous cell carcinoma antigen or the carbohydrate antigen 125. More importantly, miR-29a and miR-200a may indicate tumor histological grade and progression stage. Therefore, a 5-miRNA signature identified from genome-wide serum miRNA expression profiling may serve as a fingerprint for cervical cancer diagnosis. IntroductionCervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality in women worldwide, accounting for 9% (529,800) of total new cancer cases and 8% (275,100) of total cancer deaths among women in 2008 (1). Cervical cancer is also the major cause of death in women of reproductive age (2-4). Cervical cancer is characterized by a long period of preclinical disease progressing through a number of well-defined premalignant stages. The transition of normal epithelium to preneoplastic cervical intraepithelial neoplasia (CIN) and invasive cervical cancer may require >10 years (5). The overall survival was reported to be ~80-90% for stage Ib, 70-80% for stage II, 60% for stage III and 15% for stage IVa disease (6). From a clinical perspective, if detected prior to the point of progression to invasive disease, a variety of treatment options are available and the disease is almost certainly curable. Unfortunately, the early stages of cervical cancer are usually asymptomatic. When common signs and symptoms (such as vaginal bleeding and/or discharge and pelvic or back pain) appear, the disease is usually at an advanced stage. Furthermore, a number of these symptoms are non-specific and may represent a variety of different conditions (7).Cervical carcinoma in situ is confined to the epithelial layer; therefore, the Papanicolaou test (Pap smear) cannot effectively detect the l...

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Serum microRNAs (miRNAs), with their remarkable stability and unique concentration profiles in patients with various diseases, are promising non-invasive biomarkers for tumor detection. The present study investigated the altered profiles of serum microRNAs in patients with endometrioid endometrial cancer (EEC) in order to predict the malignancy of the disease at a relatively early stage. TaqMan® low-density arrays (TDLAs) were used to perform an analysis in the initial screening phase using serum samples pooled from seven EEC patients and 20 controls. The differential expression was validated using a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (qRT-PCR) in samples taken from 26 EEC patients and 22 age- and gender-matched healthy controls. The data obtained from the TLDAs demonstrated that 22 serum miRNAs were markedly upregulated in the EEC patients compared with the controls. The qRT-PCR analysis further identified a profile of four serum miRNAs (miR-222, miR-223, miR-186 and miR-204) as a fingerprint for EEC detection. The area under the receiver operating characteristic (ROC) curve of this four-serum miRNA signature was 0.927, which was markedly higher than that of carbohydrate antigen 125 (CA-125; 0.673). The four-miRNA signature identified by genome-wide serum miRNA expression profiling analysis provides a novel, non-invasive approach for EEC diagnosis.