Peng Wang

Comment on “Microsatellite instability as a marker of prognosis: a systematic review and meta-analysis of endometrioid endometrial cancer survival data”

ZNF251 haploinsufficiency confers PARP inhibitors resistance in BRCA1-mutated cancer cells through activation of homologous recombination

Poly (ADP-ribose) polymerase inhibitors (PARPis) represent a promising new class of agents that have demonstrated efficacy in treating various cancers, particularly those with BRCA1/2 mutations. Cancer-associated BRCA1/2 mutations disrupt DNA double-strand break (DSB) repair via homologous recombination (HR). PARP inhibitors (PARPis) have been used to trigger synthetic lethality in BRCA1/2-mutated cancer cells by promoting the accumulation of toxic DSBs. Unfortunately, resistance to PARPis is common and can occur through multiple mechanisms, including the restoration of HR and/or stabilization of replication forks. To gain a better understanding of the mechanisms underlying PARPis resistance, we conducted an unbiased CRISPR-pooled genome-wide library screen to identify new genes whose deficiency confers resistance to the PARPi olaparib. Our research revealed that haploinsufficiency of the ZNF251 gene, which encodes zinc finger protein 251, is associated with resistance to PARPis in various breast and ovarian cancer cell lines carrying BRCA1 mutations. Mechanistically, we discovered that ZNF251 haploinsufficiency leads to stimulation of RAD51-mediated HR repair of DSBs in olaparib-treated BRCA1-mutated cancer cells. Moreover, we demonstrated that a RAD51 inhibitor reversed PARPi resistance in ZNF251 haploinsufficient cancer cells harboring BRCA1 mutations. Our findings provide important insights into the mechanisms underlying PARPis resistance by highlighting the role of RAD51 in this phenomenon.

Diagnostic value of serum CA125 combined with PET/CT in ovarian cancer and tuberculous peritonitis in female patients

To evaluate the diagnostic value of serum CA125 combined with A total of 86 female patients (64 OC and 22 TBP) were included in this study. Serum CA125, PET/CT maximal intensity projection (MIP), maximal standardized uptake value, ovarian mass, ascites volume, and other indicators were analyzed and a diagnostic scoring system was established according to the weights of statistically significant indicators. Univariate analysis showed that serum CA125 in OC and TBP patients were 2079.9 ± 1651.3 U/mL and 448.3 ± 349.5 U/mL (P < 0.001). In MIP images, abdominal lesions were focal distribution in 92.2% (59/64) of OC patients and diffuse distribution in 95.5% (21/22) of TBP patients (P < 0.001). Ovarian masses could be observed in 82.8% (53/64) OC patients and 31.8% (7/22) TBP patients (P <0.001). The other indicators were not statistically significant. Logistic regression analysis showed that serum CA125 and MIP were independent risk factors for diagnosis. A diagnostic scoring system could be established based on serum CA125, MIP and ovarian mass, and the diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 98.4% (63/64), 95.5% (21/22), 97.7% (84/86), 98.4% (63/64), and 95.5% (21/22), respectively. Serum CA125 combined with PET/CT is of great value in the diagnosis of OC and TBP. A simple and efficient diagnostic scoring system can be established using serum CA125, MIP image feature, and ovarian mass.

Comment on: BRCA1 Expression by Immunohistochemistry and Prognosis in Ovarian Cancer: A Systematic Review and Meta‑Analysis

Serum Autoantibodies against LRDD, STC1, and FOXA1 as Biomarkers in the Detection of Ovarian Cancer

Purpose. This study is aimed at evaluating serum autoantibodies against four tumor-associated antigens, including LRDD, STC1, FOXA1, and EDNRB, as biomarkers in the immunodiagnosis of ovarian cancer (OC). Methods. The autoantibodies against LRDD, STC1, FOXA1, and EDNRB were measured using an enzyme-linked immunosorbent assay (ELISA) in 94 OC patients and 94 normal healthy controls (NHC) in the research group. In addition, the diagnostic values of different autoantibodies were validated in another independent validation group, which comprised 136 OC patients, 136 NHC, and 181 patients with benign ovarian diseases (BOD). Results. In the research group, autoantibodies against LRDD, STC1, and FOXA1 had higher serum titer in OC patients than NHC ( P &lt; 0.001 ). The area under receiver operating characteristic curves (AUCs) of these three autoantibodies were 0.910, 0.879, and 0.817, respectively. In the validation group, they showed AUCs of 0.759, 0.762, and 0.817 and sensitivities of 49.3%, 42.7%, and 48.5%, respectively, at specificity over 90% for discriminating OC patients from NHC. For discriminating OC patients from BOD, they showed AUCs of 0.718, 0.729, and 0.814 and sensitivities of 47.1%, 39.0%, and 51.5%, respectively, at specificity over 90%. The parallel analyses demonstrated that the combination of anti-LRDD and anti-FOXA1 autoantibodies achieved the optimal diagnostic performance with the sensitivity of 58.1% at 87.5% specificity and accuracy of 72.8%. The positive rate of the optimal autoantibody panel improved from 62.4% to 87.1% when combined with CA125 in detecting OC patients. Conclusion. Serum autoantibodies against LRDD, STC1, and FOXA1 have potential diagnostic values in detecting OC.

A Clinicopathologic Analysis of Decidual Polyps: A Potentially Problematic Diagnosis

Objective. The decidual polyp is a special cervical polyp that is not systemically reported or well known. The aim of this study was to describe the clinicopathologic features of the decidual polyps observed at the West China Second University Hospital of Sichuan University between 2015 and 2020 and to spread awareness of them. Methods. Two hundred and fifty cases of decidual polyps, accounting for 45.45% (250/550) of all cervical polyps identified during pregnancy, were reviewed. The patients were followed up until the end of their pregnancies, which delivered &lt;28 weeks and between 28 and 37 weeks, and full‐term delivery. The t‐test or nonparametric test was used to measure the data, and the chi‐square test was used for counting data. Statistical significance was set at p &lt; 0.05. Results. Most of the decidual polyps occurred during the first trimester, with a median patient age of 33 years. The polyps were both singles and multiples and located at the cervix, with a long stalk, and a median diameter of one centimeter. The gross morphological appearance varied from polypoid to lingulate, and they were fragile and bled easily. Microscopically, the decidual polyps showed diffuse glandular secretion as well as decidual changes in the stromal cells. They could be divided into two subtypes: decidua fragment and decidua with endometrial polyp formation. Seventy‐three patients who went on to have further pregnancies were followed until the end of the study period. Twenty‐one (21/73, 28.77%) of them had adverse pregnancy outcomes (12 cases delivered &lt;28 weeks and 9 cases delivered between 28 and 37 weeks). Conclusions. The data showed that the decidual polyp was the second most common cervical polyp during pregnancy, and its incidence was associated with adverse pregnancy outcomes. Thus, this type of polyp should be considered in cervical polypectomy specimens from pregnant women. A more uniform and accurate pathological diagnosis, including the thrombus status and division subtype, could provide the basis for obstetricians to promote treatment improving pregnancy outcomes.