Wei Chen

Instability in the Penta-C and Penta-D Loci in Microsatellite-Unstable Endometrial Cancer

Endometrial cancer (EC) is the most common gynecologic cancer. Early detection is one of the most important predictors of survival. The cancer is curable if detected early but the five-year survival rate in advanced cases can be as low as 22%. Microsatellite instability (MSI) testing is used to screen populations for Lynch Syndrome (LS), the most common cause of inherited EC, and to classify EC into distinct groups with unique histological, prognostic, and molecular features. Accurate sample identification is crucial for successful MSI testing because instability is assessed by comparing amplification patterns in markers in the normal and tumor samples that must be taken from the same individual. Penta-C and Penta-D pentanucleotide markers are used widely for sample identification in not only MSI testing but also parentage verification, forensic science, and population genetics studies. The objective of this study was to test 324 pairs of tumor and matched normal DNAs from EC patients for instability in these markers using the Promega MSI Analysis SystemTM considered the “gold standard” in MSI testing. Both markers were unstable, and therefore not reliable for MSI testing, in 8.2% of the EC patients with MSI. Instability in both mono- and pentanucleotide markers suggest that the tumors with MSI likely suffer from a “generalized” form of instability also affecting other short tandem repeats. Results from many studies using these markers for various purposes may not be accurate if samples with MSI are involved.

tRF-20-S998LO9D Inhibits Endometrial Carcinoma by Upregulating SESN2

The Value of P16 Protein Detection in the Screening for High‐Grade Squamous Intraepithelial and Higher Lesions of the Cervix by the Combined Detection of HR‐HPV and TCT

ABSTRACTLiquid‐based thin layer cytology (TCT) and HR‐HPV detection are the most important screening methods for cervical cancer. These two methods have limited sensitivity and specificity, so some cervical lesions are still missed or misdiagnosed. This paper mainly discusses the value of P16 protein detection in cervical cancer screening. In particular, it is effective and practical in high‐grade squamous epithelial and above cervical lesions (CINII+). In this retrospective study, the diagnostic specificity and positive predictive value (PPV) of P16 protein detection for cervical CINII+ lesions were significantly higher than that of TCT and HR‐HPV detection, and the accuracy was the highest. P16 protein detection can also reduce the rate of missed diagnoses in HR‐HPV‐negative patients and reduce unnecessary colposcopic biopsies. Our data highlight the feasibility and significance of P16 protein detection in cervical disease screening.

RETRACTED: Preliminary Evaluation of the Value of a Small‐Molecule Probe Targeting DNMT1 in Detecting the Methylation of PAX1 in Cervical Cancer

ABSTRACT Background To investigate the screening value of a small‐molecule probe to assess the methylation of PAX1 in cervical cancer. Materials and Methods The diagnostic threshold of the grayscale values for cervical lesions was assessed by plotting the Receiver Operating Characteristic (ROC) curve of subjects. Grayscale values were significantly different among the four groups ( p  < 0.05). Compared with the LSIL and cervicitis groups, a considerably higher grayscale value was found in the CA and high‐grade squamous intraepithelial lesion (HSIL) groups (both p  < 0.05). Results The differential ROC curves of the grayscale values showed that the diagnostic Area Under Curve of the probe for cervicitis and low‐grade squamous intraepithelial lesion (LSIL) was 0.8724 (95% CI = 0.7762–0.9685, p  < 0.0001), for cervicitis and CA was 1.0000 ( p  < 0.0001), for the LSIL and HSIL was 0.5484 (95% CI = 0.3826–0.7142, p  = 0.5755), and for the LSIL and CA was 0.7724 (95% CI = 0.6016–0.9432, p = 0.0138). Conclusion The small molecular probe has certain application value in differentiating the type of cervical lesions and has better efficacy in distinguishing cervical inflammatory and precancerous lesions from carcinogenesis, but less efficacy in determining the type of precancerous lesions.

Efficacy and safety of low‐dose apatinib in ovarian cancer patients with platinum‐resistance or platinum‐refractoriness: A single‐center retrospective study

AbstractBackgroundThis study aimed to evaluate the efficacy and safety of apatinib with a low dose of 250 mg/d in the treatment of platinum‐resistant or platinum‐refractory ovarian cancer patients.MethodsPatients with platinum‐resistant or platinum‐refractory ovarian carcinoma treated with 250 mg/d apatinib in our institution from November 2016 to December 2017 were retrospectively reviewed. The tumor response and progression were evaluated according to the standard by incorporating the levels of CA125 and Response Evaluation Criteria in Solid Tumors 1.1. CTCAE 4.03 was used to evaluate adverse events (AEs).ResultsFifty‐two eligible patients were enrolled in per‐protocol (PP) analysis and 65 patients (including 13 lost to follow‐up) were included in the intention‐to‐treat (ITT) analysis. In PP analysis, 18 patients (34.6%) had partial response (PR), 22 patients (42.3%) had stable disease (SD), and the disease control rate (DCR) was 61.5%. Median progression‐free survival (PFS) was 4.0 months (95% CI, 2.83‐5.17 m), and median overall survival (OS) was 25.33 months (95% CI, 17.74‐32.92 m). The objective response rate and DCR for patients in ITT analysis were 27.7% and 49.2%, respectively. The top three treatment‐related AEs were hypertension, hand‐foot syndrome, and leukopenia. Eight patients (15.4%) in PP population had grade 3 treatment‐related AEs. Previous chemotherapy lines, number of recurrences, and AEs did not affect the efficacy of apatinib. Age older than 60 was associated with higher rates of disease control and prolonged PFS (P < .05).ConclusionApatinib 250 mg/d is a feasible treatment in platinum‐resistant or platinum‐refractory epithelial ovarian cancer (EOC) patients.

Risk Stratification of Early-Stage Cervical Cancer with Intermediate-Risk Factors: Model Development and Validation Based on Machine Learning Algorithm

Abstract Background Adjuvant therapy for patients with cervical cancer (CC) with intermediate-risk factors remains controversial. The objectives of the present study are to assess the prognoses of patients with early-stage CC with pathological intermediate-risk factors and to provide a reference for adjuvant therapy choice. Materials and Methods This retrospective study included 481 patients with stage IB–IIA CC. Cox proportional hazards regression analysis, machine learning (ML) algorithms, Kaplan-Meier analysis, and the area under the receiver operating characteristic curve (AUC) were used to develop and validate prediction models for disease-free survival (DFS) and overall survival (OS). Results A total of 35 (7.3%) patients experienced recurrence, and 20 (4.2%) patients died. Two prediction models were built for DFS and OS using clinical information, including age, lymphovascular space invasion, stromal invasion, tumor size, and adjuvant treatment. Patients were divided into high-risk or low-risk groups according to the risk score cutoff value. The Kaplan-Meier analysis showed significant differences in DFS (p = .001) and OS (p = .011) between the two risk groups. In the traditional Sedlis criteria groups, there were no significant differences in DFS or OS (p > .05). In the ML-based validation, the best AUCs of DFS at 2 and 5 years were 0.69/0.69, and the best AUCs of OS at 2 and 5 years were 0.88/0.63. Conclusion Two prognostic assessment models were successfully established, and risk grouping stratified the prognostic risk of patients with CC with pathological intermediate-risk factors. Evaluation of long-term survival will be needed to corroborate these findings. Implications for Practice The Sedlis criteria are intermediate-risk factors used to guide postoperative adjuvant treatment in patients with cervical cancer. However, for patients meeting the Sedlis criteria, the choice of adjuvant therapy remains controversial. This study developed two prognostic models based on pathological intermediate-risk factors. According to the risk score obtained by the prediction model, patients can be further divided into groups with high or low risk of recurrence and death. The prognostic models developed in this study can be used in clinical practice to stratify prognostic risk and provide more individualized adjuvant therapy choices to patients with early-stage cervical cancer.

Phenolic Compounds from Polygonum chinense Induce Growth Inhibition and Apoptosis of Cervical Cancer SiHa Cells

Cervical cancer is considered to be one of the most serious malignant tumors in women. Natural compounds have been considered as important sources in the search for new anticancer agents. Polygonum chinense (PC) has been used as herbal medicine and Chinese cool tea. By activity‐guided of the extracts from PC, PCwater shows good growth inhibition on SiHa cell, then by chromatographic analysis (HPLC and HPLC‐MS/MS), we found twelve components, seven were phenolic compounds (PHE), two PHE named ellagic acid and corilagin were found to show strong growth inhibition effects in SiHa cell dose‐dependently, while the seven phenolic compounds showed low inhibition on the common human HcerEpic cell. Further research found ellagic acid and corilagin induced G2 phase cell cycle arrest by upregulating levels of P53, Bcl‐2, caspase 3, and caspase 9, while the Bax was reduced. These results suggested that PHE from PC might have potential anticancer effects against SiHa cells by acting through the apoptosis pathway, PHE from PC might have the potential to be used as a nutraceutical for the prevention and treatment of ovarian cancer.