Xiaojian Yan

Construction and validation of a novel aging‐related gene signature and prognostic nomogram for predicting the overall survival in ovarian cancer

AbstractBackgroundOvarian cancer (OC) is the most lethal gynecological malignancy. The objective of this study was to establish and validate an individual aging‐related gene signature and a clinical nomogram that can powerfully predict independently the overall survival rate of patients with ovarian cancer.MethodsData on transcriptomic profile and relevant clinical information were retrieved from The Cancer Genome Atlas (TCGA) database as a training group, and the same data from three public Gene Expression Omnibus (GEO) databases as validation groups. Univariate Cox regression analysis, lasso regression analysis, and multiple multivariate Cox analysis were analyzed sequentially to select the genes to be included in the aging‐associated signature. A risk scoring model was established and verified, the predictive value of the model was evaluated, and a clinical nomogram was established.ResultsWe found eight genes that were most relevant to prognosis and constructed an eight‐mRNA signature. Based on the model, each OC patient's risk score was able to be calculated and patients were split into groups of low and high risks with a distinct outcome. Survival analysis confirmed that the outcome of patients in the high‐risk group was dramatically shorter than that of those in the low‐risk group, and the eight‐mRNA signature can be considered as a powerful and independent predictor that could predict the outcome of OC patient. Additionally, the risk score and age can be used to construct a clinical nomogram as a simpler tool for predicting prognosis. We also explored the association between the risk score and immunity and drug sensitivity.ConclusionThis study suggested that the aging‐related gene signature could be used as an intervention point and latent prognostic predictor in OC, which may provide new perceptions for postoperative treatment strategies.

Identification and validation of a six-gene signature associated with glycolysis to predict the prognosis of patients with cervical cancer

AbstractBackgroundCervical cancer (CC) is one of the most common gynaecological cancers. The gene signature is believed to be reliable for predicting cancer patient survival. However, there is no relevant study on the relationship between the glycolysis-related gene (GRG) signature and overall survival (OS) of patients with CC.MethodsWe extracted the mRNA expression profiles of 306 tumour and 13 normal tissues from the University of California Santa Cruz (UCSC) Database. Then, we screened out differentially expressed glycolysis-related genes (DEGRGs) among these mRNAs. All patients were randomly divided into training cohort and validation cohort according to the ratio of 7: 3. Next, univariate and multivariate Cox regression analyses were carried out to select the GRG with predictive ability for the prognosis of the training cohort. Additionally, risk score model was constructed and validated it in the validation cohort.ResultsSix mRNAs were obtained that were associated with patient survival. The filtered mRNAs were classified into the protective type (GOT1) and the risk type (HSPA5, ANGPTL4, PFKM, IER3 and PFKFB4). Additionally, by constructing the prognostic risk score model, we found that the OS of the high-risk group was notably poorer, which showed good predictive ability both in training cohort and validation cohort. And the six-gene signature is a prognostic indicator independent of clinicopathological features. Through the verification of PCR, the results showed that compared with the normal cervial tissuses, the expression level of six mRNAs were significantly higher in the CC tissue, which was consistent with our findings.ConclusionsWe constructed a glycolysis-related six-gene signature to predict the prognosis of patients with CC using bioinformatics methods. We provide a thorough comprehension of the effect of glycolysis in patients with CC and provide new targets and ideas for individualized treatment.

Predictive role of serum cholesterol and triglycerides in cervical cancer survival

Lipids have been evaluated for their possible role in cancer survival prediction. The aim of the current study was to investigate the prognostic value of lipids on overall survival for stage IB1-IIA2 cervical cancer patients. A retrospective study including cervical cancer patients with early-stage (FIGO 2009 stage IB1-IIA2) disease was conducted from January 2012 to February 2017. Patients with any history of liver disease or other cancers, and patients who took any medications known to influence lipid metabolism, were excluded. We measured various factors in patients' lipid profiles including total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein, and assessed these four parameters together with clinicopathological features to identify the significant prognostic factors for overall survival. A total of 583 patients with median age 53 (range 25-82) years were included. Among them, 283 (48.5%) patients were in FIGO stage IB1, 44 patients (7.6%) in stage IB2, 189 (32.4%) patients in stage IIA1, and the remaining 67 (11.5%) patients were in stage IIA2. Using univariable Cox proportional hazard analysis and subsequent multivariable analysis, total cholesterol, triglycerides, and pelvic lymph node status were shown to be independent prognostic factors for overall survival (p<0.05 for all). Furthermore, the results of the Kaplan-Meier survival curves showed that both the high total cholesterol group and the high triglycerides group were associated with worse overall survival (p=0.002 and p=0.001, respectively) CONCLUSIONS: Our study showed that total triglycerides and total cholesterol may serve as potential predictors for overall survival in patients with cervical cancer. Cervical cancer patients may benefit from treatments after adjusting their triglycerides and total cholesterol levels.

Comparison of laparoscopic and open radical hysterectomy in cervical cancer patients with tumor size ≤2 cm

There is recent evidence that demonstrates worse oncologic outcomes associated with minimally invasive radical hysterectomy when compared with open radical hysterectomy, particularly in patients with tumors >2 cm. The aim of our study was to retrospectively evaluate the oncological outcomes between laparoscopic and open radical hysterectomy in International Federation of Gynecology and Obstetrics(FIGO) 2009 stage IB1 (FIGO 2009) cervical cancer patients with tumor size ≤2 cm. A retrospective review of medical records was performed to identify patients who underwent either laparoscopic or open radical hysterectomy during January 2010 and December 2018. Inclusion criteria were: (1) histologically confirmed cervical cancer including all histological types; (2) FIGO 2009 stage IB1; (3) tumor size ≤2 cm (determined by pelvic examination, magnetic resonance imaging or transvaginal ultrasound); (4) had undergone radical hysterectomy (type II or III) with pelvic and/or para-aortic lymphadenectomy as primary surgical treatment; (5) had follow-up information. Patients with FIGO 2009 stage IA1 or IA2, tumor size >2 cm, or who received neo-adjuvant chemotherapy before surgery, those with cervical cancer incidentally found after simple hysterectomy, or with insufficient data were excluded. Concurrent comparison between the laparoscopic and open cohorts was made for disease-free survival and overall survival. A total of 325 cervical cancer patients were included; of these, 129 patients underwent laparoscopic surgery and 196 patients had open surgery. The median follow-up times were 51.8 months (range 2-115) for laparoscopic surgery and 49.5 months (range 3-108) for open surgery. Patients in the laparoscopic group had significantly worse 5 year disease-free survival than those in the open group (90.4% vs 97.7%; p=0.02). There was no significant difference in 5 year overall survival between groups (96.9% vs 99.4%, p=0.33). The Cox proportional hazards regression analysis indicated that laparoscopic surgery was associated with lower disease-free survival compared with open surgery (adjusted hazard ratio 4.64, 95% CI 1.26 to 17.06; p=0.02). In patients with non-squamous cell carcinoma or with grade II-III, laparoscopic surgery had a significantly worse 5 year disease-free survival compared with the open surgery group (74% vs 100%, p=0.01, and 88.8% vs 98.0%, p=0.02, respectively). Laparoscopic radical hysterectomy was associated with worse disease-free survival for stage IB1 (FIGO 2009) cervical cancer patients with tumor size ≤2 cm compared with open radical hysterectomy. Further studies may shed additional light on the impact of minimally invasive surgery in this low-risk patient population.

Clinical features and prognostic factors of cervical villoglandular adenocarcinoma

Villoglandular adenocarcinoma is a rare sub-type of cervical adenocarcinoma. To analyze the clinicopathological features and evaluate the prognosis of patients with villoglandular adenocarcinoma of the cervix. Patient characteristics, procedure, pathology, and surgical outcomes were retrospectively reviewed in patients with villoglandular adenocarcinoma between November 2006 and June 2019 from multiple centers in China. In order to explore the difference between villoglandular adenocarcinoma and routine adenocarcinoma, patients (FIGO 2009 stage IA1-IB2) who had complete data during the same time period were included. A total of 60 patients with villoglandular adenocarcinoma and 104 with standard adenocarcinoma were included. The median age of the patients with villoglandular adenocarcinoma was 42 years (range 27-68). The most common 2009 FIGO stage was IB1 in 39 (65%) patients with villoglandular adenocarcinoma. A total of 23 patients underwent laparoscopic surgery (two total hysterectomies, 21 radical hysterectomies) and the other 37 patients underwent laparotomy (three total hysterectomies, 34 radical hysterectomies). A total of 56 patients underwent lymphadenectomy and three (5.4%) had positive lymph nodes. Fifteen (25%) patients had one or both ovaries preserved. Seven patients were lost to follow-up. The median follow-up time for the entire group was 50.2 months (range 5.1-154.6). No deaths or recurrences occurred. Excluding six patients with FIGO 2009 stage II, the 5-year disease-free survival of the 47 patients with villoglandular adenocarcinoma with FIGO 2009 stage I for whom there was follow-up, was significantly higher than that of the 104 patients with standard cervical adenocarcinoma (100% vs 92.2%, log-rank p=0.039). However, the 5-year overall survival of the two groups did not differ (100% vs 95.7%, log-rank p=0.11). Villoglandular adenocarcinoma has a favorable prognosis. Further studies are needed to provide more details of treatment strategies and prognosis.