Jianhua Qian

Identification and validation of a seven cuproptosis-associated lncRNA signature to predict the prognosis of endometrial cancer

Objective Endometrial cancer (EC) is one of the most prevalent cancers in women. Long non-coding RNAs (lncRNAs) are potential diagnostic biomarkers in patients with EC. Methods We obtained clinical information and transcriptome data for 552 patients with EC from The Cancer Genome Atlas database. Cuproptosis-associated lncRNAs were obtained through Pearson’s correlation analysis. Univariate and multivariate Cox regression analyses were applied and a signature predicting overall survival (OS) among patients with EC was constructed. We also analyzed the tumor immune microenvironment and drug sensitivity. The results were validated by quantitative real time-polymerase chain reaction, and 5-ethynyl-2′-deoxyuridine and wound-healing assays. Results Seven cuproptosis-associated lncRNAs related to prognosis were screened out and a signature was constructed. OS was significantly superior in the low-risk group. In addition, patients in the low-risk group had more CD8+ T cell infiltration, a stronger type II interferon response, and greater cisplatin sensitivity. Expression levels of some of the lncRNAs were significantly increased by cuproptosis. Furthermore, silencing of lncRNA AC084117.1 significantly inhibited the proliferation and migration of EC cells. Conclusion We constructed a seven cuproptosis-associated lncRNA signature to predict the prognosis of patients with EC with good predictive power.

Generation and characterization of human iPSC lines (FAHZJUi001-A and FAHZJUi002-A) from two familial recurrent hydatidiform mole patients carrying homozygous mutation in the NLRP7 gene

Hydatidiform mole (HM) is a pathological pregnancy characterized by excessive trophoblast proliferation and the absence of embryonic tissue development, predominantly sporadic in onset. Recurrent hydatidiform mole (RHM) affects approximately 1%-4% of HM patients, among which familial RHM (FRHM) is extremely rare and classified as a monogenic autosomal recessive disorder. NLRP7 (NLR family, pyrin domain containing 7) is the major pathogenic gene for RHM, in which affected individuals have a profound impairment in fertility and a markedly elevated risk of malignant transformation. Yet mechanistic research remains constrained by ethical limitations in human embryo studies and the absence of animal models recapitulating HM phenotypes. Here, we report the generation and characterization of iPSC lines from FRHM patients harboring homozygous NLRP7 variants c.2078G > A (p.Arg693Gln) and c.2161 C > T (p.Arg721Trp), respectively. These cellular models offer a unique platform to dissect molecular pathways driving NLRP7-mediated reproductive failure, overcoming long-standing barriers in FRHM pathogenesis research.

Reappraisal and refined diagnosis of ultrasonography and histological findings for hydatidiform moles: a multicentre retrospective study of 821 patients

AimsSpecific identification of a hydatidiform mole (HM) and subclassification of a complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) are critical. This study aimed to reappraise the diagnostic performance of ultrasonography and histology with a refined diagnosis.MethodsThis was a retrospective, multicentre cohort study of 821 patients with histologically suspected HM specimens. Refined diagnostic algorithms with p57 immunohistochemistry and short tandem repeat (STR) genotyping were performed and used as the true standard for assessing the diagnostic performance of the original ultrasonography and morphology methods. The diagnostic performance was calculated using accuracy, agreement rate, sensitivity and the positive predictive value (PPV) compared with refined diagnostic results.ResultsOf the 821 histologically suspected HM cases included, 788 (95.98%) were successfully reclassified into 448 CHMs, 213 PHMs and 127 non-molar (NM) abortuses. Ultrasonography showed an overall accuracy of 44.38%, with a sensitivity of 44.33% for CHM and 37.5% for PHM. The overall classification accuracy of the original morphological diagnosis was 65.97%. After exclusion of the initially untyped HMs, the overall agreement rate was 59.11% (κ=0.364, p<0.0001) between the original and refined diagnoses, with a sensitivity of 40.09% and PPV of 96.05% for diagnosing CHMs and a sensitivity of 84.98% and a PPV of 45.59% for diagnosing PHMs. The interinstitutional variability of morphology in diagnosing HMs was significant among the 15 centres (range, 8.33%–100.00%, p<0.0001).ConclusionThe current diagnosis of HM based solely on ultrasound or morphology remains problematic, and ancillary techniques, particularly p57 immunohistochemistry and DNA genotyping, should be integrated into routine practice as much as possible.