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ObjectiveTo explore the ability of PAX1 methylation (PAX1m) to predict the pathological upgrade of cervical intraepithelial neoplasia (CIN) before cold knife conization (CKC).MethodsA total of 218 women that underwent colposcopy-directed biopsy (CDB) pathology for the confirmation of CIN2 and CIN3 between December 2020 to September 2021 were enrolled in this study. The methylation levels of PAX1 (ΔCpPAX1) were determined by quantitative methylation-specific polymerase chain reaction (qMSP). Receiver operating characteristic curve was used to identify the optimal cut-off value of ΔCpPAX1 for predicting the pathological upgrade of disease.ResultsIn the CDB-confirmed CIN2 group, 36% of CIN2 was found to have pathologically upgraded to CIN3 and 30% regressed to low-grade squamous intraepithelial lesion (LSIL) and below, and none of CIN2 upgraded to early-stage cervical cancer (ESCC) after CKC. In the CDB-confirmed CIN3 group, 19.5% (23/118) of CDB-confirmed CIN3 were pathologically upgraded to ESCC after CKC. Regardless of CIN2 or CIN3, the ΔCpPAX1 level of women with upgraded pathology after CKC was significantly lower than that of women with degraded pathology. The optimal △CpPAX1 cut-off value in predicting CIN3 to be upgraded to ESCC after CKC was 6.360 and the area under the curve (AUC) was 0.814, with similar sensitivity (78.3%) and higher specificity (84.2%) than cytology≥LSIL (Se:78.3%;Sp:58.9%) and HPV16/18 positive (Se:73.9%;Sp:46.3%) patients.ConclusionsPAX1m could be a promising auxiliary marker in predicting the pathological upgrade of CIN before CKC. We found that if the △Cp PAX1 cut-off value is lower than 6.360, it is highly suggestive of invasive cervical cancer.

Methyglyoxal (MGO), an essential endogenous dicarbonyl metabolite, can lead to multiple physiological problems including hyperglycemia, kidney diseases, malignant tumors, beyond its normal concentration range. The glyoxalase system, making MGO maintained at a low level, links glycation to carcinogenesis, growth, metastasis, and cancer chemotherapy. The glyoxalase system comprises glyoxalase 1 (Glo1) and glyoxalase 2 (Glo2), which is often overexpressed in various tumor tissues. However, very little is known about the glyoxalase system in breast cancer and gynecological cancer. In this review, we introduce the role of the glyoxalase system in breast cancer, endometrial cancer, ovarian cancer and cervical cancer, and highlight the potential of the glyoxalase system to be both as a marker for diagnosis and a novel target for antitumor therapy. However, the intrinsic molecular biology and mechanisms of the glyoxalase system in breast cancer and gynecological cancer need further exploration.

BackgroundAccurate assessment of predictive biomarker expression is critical in patient selection in clinical trials or clinical practice. However, changes in biomarker expression may occur after treatment. The aim of the present study was to evaluate the effects of chemotherapy on MET expression in gastric cancer (GC).MethodsMET expression was examined immunohistochemically before and after treatment in 122 patients with unresectable or recurrent GC, and was evaluated according to H-score or the scoring criteria used in the MetMAb trial. MET gene amplification was assessed by chromogenic in situ hybridization (CISH). The antitumor effect of MET targeted therapy was investigated in human gastric cancer cells in vitro and in vivo, and the underlying molecular mechanisms were analyzed by western blot.ResultsMET expression was associated with Lauren classification as well as tumor differentiation by either scoring system. MET amplification was not associated with clinical characteristics. Of the 71 patients who had paired pre- and post-treatment tumor tissues, 28 patients (39%) were initially positive for MET expression, and 43 (61%) were negative. Twenty-five patients (35%) showed significant changes in MET expression after treatment (P=0.007). Additionally, there was a concomitant overexpression of MET and HER2 in a subset of GC patients. MET inhibitor volitinib could significantly inhibit cell proliferation and xenograft growth in vitro and in vivo in MKN45 cells with MET and phosphorylated MET (pMET) high expressions via suppressing downstream PI3K/Akt and MAPK signaling pathways. Furthermore, combination therapy targeting both MET and HER2 demonstrated a synergistic antitumor activity.ConclusionsMET expression is altered post chemotherapy and MET status should be evaluated in real-time. Both MET and pMET expressions might need to be considered for patients suitable for volitinib treatment.

BackgroundThe Cancer Genome Atlas (TCGA) project shed light on the vital role of tumor molecular features in predicting endometrial cancer patients’ prognosis. This study aims to investigate the survival impact of surgical approaches on patients with different genetic alterations.Methods473 endometrial cancer patients from TCGA database were selected. To analyze the prognostic impact of surgical approach, survival analyses were conducted in patients with different molecular features. Finally, a simplified molecular stratification model was established to select patients suitable for open or minimally invasive surgery (MIS).ResultsIn our cohort, 291 patients received open surgery and 182 received MIS. Molecular features influenced patients’ survival after different surgical approaches. Based on survival analyses, three molecular subtypes were generated, with subtype 1 harboring POLE mutation (POLEmt), microsatellite-instability high (MSI-H), homologous recombination repair (HRR) pathway mutation or MUC16 mutation (MUC16mt); subtype 3 carrying TP53 mutation; and subtype 2 without specific molecular feature. The survival influence of molecular subtypes depended on surgical approaches. In the open surgery cohort, three subtypes showed similar survival outcome, while in the MIS cohort, prognosis varied significantly among three subtypes, with subtype 1 the best and subtype 3 the worst. In stepwise Cox regression, molecular subtype was an independent predictor of recurrence-free survival in patients receiving MIS (p < 0.001).ConclusionThe molecular features of endometrial cancer are associated with patients’ prognosis after different surgical approaches. MIS should be recommended in patients with POLEmt, MSI-H, HRR pathway mutation or MUC16mt, while for patients with TP53 mutation, open surgery is better concerning oncological safety.