It is often helpful to classify biomarker values into groups of different risk levels to facilitate evaluation of a biological, physiological, or pathological state. Stratification of patients into two risk groups is commonly seen, but there is always need for more than two groups for fine assessment. So far, there are no standard methods or tools to help decide how many cutoff points are optimal. In this study, we developed a comprehensive package that included methods to determine both the optimal number and locations of cutoff points for both survival data and dichotomized outcome. We illustrated workflow of this package with data from 797 patients with cervical cancer. By analyzing several risk factors of cervical cancer such as tumor size, body mass index (BMI), number of lymph nodes involved and depth of stromal invasion, in relation to survival and clinical outcome such as lymph nodal metastasis and lymphovascular invasion, we demonstrated that the best choice for BMI and stromal invasion was two cutoff points and one for the others. This study provided a useful tool to facilitate medical decisions and the analyses on cervical cancer may also be of interest to gynecologists. The package can be freely downloaded.

Infection-induced chronic inflammation is common in patients with endometriosis. Although microbial communities in the reproductive tracts of patients have been reported, little was known about their dynamic profiles during disease progression and complication development. Microbial communities in cervical mucus were collected by cervical swabs from 10 healthy women and 23 patients, and analyzed by 16S rRNA amplicon sequencing. The abundance, ecological relationships and functional networks of microbiota were characterized according to their prevalence, clinical stages, and clinical features including deeply infiltrating endometriosis (DIE), CA125, pain score and infertility. Cervical microbiome can be altered during endometriosis development and progression with a tendency of increased Firmicutes and decreased Actinobacteria and Bacteroidetes. Distinct from vaginal microbiome, upregulation of Lactobacillus, in combination with increased Streptococcus and decreased Dialister, was frequently associated with advanced endometriosis stages, DIE, higher CA125 levels, severe pain, and infertility. Significantly, reduced richness and diversity of cervical microbiome were detected in patients with more severe clinical symptoms. Clinical treatments against infertility can partially reverse the ecological balance of microbes through remodeling nutrition metabolism and transport and cell-cell/cell-matrix interaction. This study provides a new understanding on endometriosis development and a more diverse cervical microbiome may be beneficial for patients to have better clinical outcomes.

Cervical cancer is a common gynecological malignancy, accounting for 10% of all gynecological cancers. Recently, targeted therapy for cervical cancer has shown unprecedented advantages. Several studies have shown that ubiquitin conjugating enzyme E2 (UBE2C) is highly expressed in a series of tumors, and participates in the progression of these tumors. However, the possible impact of UBE2C on the progression of cervical squamous cell carcinoma (CESC) remains unclear. Here, we carried out tissue microarray analysis of paraffin-embedded tissues from 294 cervical cancer patients with FIGO/TNM cancer staging records. The results indicated that UBE2C was highly expressed in human CESC tissues and its expression was related to the clinical characteristics of CESC patients. Overexpression and knockdown of UBE2C enhanced and reduced cervical cancer cell proliferation, respectively, in vitro. Furthermore, in vivo experiments showed that UBE2C regulated the expression and activity of the mTOR/PI3K/AKT pathway. In summary, we confirmed that UBE2C is involved in the process of CESC and that UBE2C may represent a molecular target for CESC treatment.

This paper investigates the expression of the CREB1 gene in ovarian cancer (OV) by deeply excavating the gene information in the multiple databases and the mechanism thereof. In short, we found that the expression of the CREB1 gene in ovarian cancer tissue was significantly higher than that of normal ovarian tissue. Kaplan–Meier survival analysis showed that the overall survival was significantly shorter in patients with high expression of the CREB1 gene than those in patients with low expression of the CREB1 gene, and the prognosis of patients with low expression of the CREB1 gene was better. The CREB1 gene may play a role in the occurrence and development of ovarian cancer by regulating the process of protein. Based on differentially expressed genes, 20 small-molecule drugs that potentially target CREB1 with abnormal expression in OV were obtained from the CMap database. Among these compounds, we found that naloxone has the greatest therapeutic value for OV. The high expression of the CREB1 gene may be an indicator of poor prognosis in ovarian cancer patients. Targeting CREB1 may be a potential tool for the diagnosis and treatment of OV.

Aim: To evaluate the usefulness of serum squamous-cell carcinoma antigen (SCC-Ag) and 2-[¹⁸F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) for the detection of recurrent squamous-cell carcinoma (SqCC) of the uterine cervix, and its prediction of patient survival. Methods: FDG-PET/CT was performed for patients with serum SCC-Ag levels elevated to ≥1.5 ng/mL (Group 1) and those with suspicious recurrences without any increase in serum SCC-Ag levels (Group 2). The results were analyzed on the basis of histological data, disease progression and/or clinical follow-up. Recurrence was defined as evidence of recurrent lesions within 6 months of FDG-PET/CT. The outcome was determined using medical records. Results: In total, 88 consecutive patients with cervical SqCC cancer with suspected recurrence (62 in Group 1 and 26 in Group 2) were enrolled. Recurrences were observed in 55 patients (77.4% (48/62) in Group 1 vs. 26.9% (7/26) in Group 2, p < 0.001). The overall sensitivity, specificity and accuracy of serum SCC-Ag were 87.3%, 57.6% and 76.1%, respectively, and those of FDG-PET/CT were 98.2%, 90.9% and 95.5%, respectively; the corresponding values were 97.9%, 92.9% and 96.8% for Group 1 and 100%, 89.5% and 92.3% for Group 2. Surgical resection was performed for 16 patients. At the end of the study, 40.3% (25/62) of Group 1 patients and 88.5% (23/26) of Group 2 patients were alive (p < 0.001). The survival of patients who underwent surgical resection for recurrent tumors was higher than that of patients who did not undergo resection (62.5% (10/16) vs. 17.9% (7/39), p = 0.001). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from FDG-PET/CT showed significantly different in-patient survival. Conclusions: Serum SCC-Ag could predict tumor recurrence and the survival of patients with SqCC cervical cancer. As such, the surgical resection of limited recurrent disease, as determined using FDG-PET/CT, might improve the survival of patients with cervical cancer. MTV and TLG may serve as a prognostic biomarker of survival in patients with recurrent cervical cancer.