Ying Chen

Significance of TP53 Mutational Status‐Associated Signature in the Progression and Prognosis of Endometrial Carcinoma

Background. TP53 mutations are associated with poor outcome for patients with endometrial carcinoma (EC). However, to date, there have been no studies focused on the construction of TP53 mutational status‐associated signature in EC. In this study, we aim to conduct a TP53 mutation‐associated prognostic gene signature for EC. Methods. Hence, we explored the mutational landscape of TP53 in patients with EC based on the simple nucleotide variation data downloaded from The Cancer Genome Atlas (TCGA) database. Differential expression analysis and least absolute shrinkage and selection operator (LASSO)–Cox analysis was used to establish TP53 mutation‐associated prognostic gene signature. The overall survival rate between the high‐risk and low‐risk groups was compared by the Kaplan–Meier (K‐M) method. Results. We found that the TP53 mutation was associated with poor outcome, older age, lower BMI, and higher grade and stage of EC in patients. A TP53 mutational status‐associated signature was established based on transcriptome profiling data. Moreover, the patients in TCGA database were categorized into high‐ and low‐risk groups. Kaplan–Meier (K‐M) analysis indicated that the patients in the high‐risk group have poor survival outcome. Furthermore, receiver operating characteristic (ROC) curves confirmed the robust prognostic prediction efficiency of the TP53 mutational status‐associated signature. Finally, the prognostic ability was successfully verified in the other two datasets from cBioPortal database as well as in 60 clinical specimens. Univariate (hazard ratio (HR) = 1.041, 95%CI = 1.031–1.051, p < 0.001) and multivariate (hazard ratio (HR) = 1.029, 95%CI = 1.018–1.040, p < 0.001) Cox regression analyses indicated that the TP53 mutational status‐associated signature could be used as an independent prognostic factor for EC patients. Conclusion. In summary, our research constructed a powerful TP53 mutational status‐associated signature that could be a potential novel prognostic biomarker and therapeutic target for EC.

Molecular and Immune Correlates of Response to First-Line De-escalated Chemotherapy plus Penpulimab and Anlotinib in Advanced Cervical Cancer

Abstract The standard of care for advanced cervical cancer includes chemotherapy, antiangiogenic, and/or immune checkpoint blockade regimens. Although effective, it leads to pleiotropic side effects. Deescalation chemotherapy together with immunotargeted therapies has been proven effective and less toxic in other cancers. In this study, we conducted a multicenter, single-arm, phase II study of first-line deescalated platinum-based chemotherapy plus anlotinib and penpulimab, followed by maintenance therapy solely with anlotinib and penpulimab in patients with PD-L1–positive, persistent, recurrent, or metastatic cervical cancer. Of 32 efficacy-evaluable patients, 30 (93.8%, 95% confidence interval, 79.2%–99.2%) had an investigator-confirmed objective response. Single-nucleus RNA sequencing implied enhanced chemotaxis and proliferative activity of tumor-infiltrating T cells, and activated germinal center B cells portended optimal treatment response. Patients with a high tertiary lymphoid structure-to-tumor area ratio exhibited better survival. Our findings lay the groundwork for the feasibility of first-line de-escalated chemotherapy plus anlotinib and penpulimab in patients with metastatic, persistent, or recurrent cervical cancer. Significance: We recruited 34 patients with advanced cervical cancer receiving two cycles of platinum-based chemotherapy plus anlotinib and penpulimab, followed by maintenance therapy solely with anlotinib and penpulimab, and showed safety and efficacy of this deescalation regimen. This work highlights the potential for personalized treatment strategies and feasibility of reduced-toxicity regimens.

Quantitative Proteomics Reveal the Mechanism of MiR-138–5p Suppressing Cervical Cancer via Targeting ZNF385A

MicroRNAs are short, noncoding RNA molecules that exert pivotal roles in cancer development and progression by modulating various target genes. There is growing evidence that miR-138-5p is significantly involved in cervical cancer (CC). However, its precise molecular mechanism has yet to be fully understood. In the current investigation, a quantitative proteomics approach was utilized to detect possible miR-138-5p targets in HeLa cells systematically. In total, 364 proteins were downregulated, and 150 were upregulated after miR-138-5p overexpression. Bioinformatic analysis of these differentially expressed proteins (DEPs) revealed significant enrichment in several cancer-related pathways. Zinc finger protein 385A (ZNF385A) was determined as a novel direct target of miR-138-5p and discovered to facilitate the proliferation, migration, and cell cycle progression of HeLa cells. SFN and Fas cell surface death receptor(FAS) were then identified as functional downstream effectors of ZNF385A and miR-138-5p. Moreover, a tumor xenograft experiment was conducted to validate the association of miR-138-5p-ZNF385A-SFN/FAS axis with the development of CC

Development and validation of nomograms to predict survival of primary cervical lymphoma: A surveillance, epidemiology, and end results (SEER) database analysis

Due to the rarity of primary cervical lymphoma (PCL), the long-term survival of patients with cervical lymphoma and factors influencing survival are unknown. This study aimed to compare the survivals of patients with PCL and those with other cervical tumors and construct a clinical prediction model to assess the prognosis of patients with PCL. Patients with PCL from the Surveillance, Epidemiology, and End Results database were allocated randomly in a 7:3 ratio to the training and validation sets. Cox proportional hazard and Fine-Gray models were used to verify independent factors influencing overall survival (OS) and disease-specific survival (DSS), and nomograms were constructed. Receiver operating characteristic curve analysis and decision curve analysis (DCA) were used to test the performance and clinical utility of the models, respectively. We included 206 patients with PCL. The areas under the curves (AUCs) and DCA showed that all models had clinical benefits; The models constructed in this study had a predictive performance for patients with PCL. It can guide clinicians to rationalize the treatment plan for patients.

Novel Hybrids of 3-Substituted Coumarin and Phenylsulfonylfuroxan as Potent Antitumor Agents with Collateral Sensitivity against MCF-7/ADR

Twenty-three new coumarin-furoxan hybrids were synthesized, which exhibited nanomole antiproliferation activities in A2780, A2780/CDDP, MCF-7/ADR, and MDA-MB-231. Among them, compound

Prediction of Immunotherapy Response and Prognostic Outcomes for Patients With Ovarian Cancer Using PANoptosis‐Related Genes

BackgroundOvarian cancer (OC) is a lethal malignancy often diagnosed at a late stage with frequent recurrence and immunotherapy resistance. PANoptosis is a novel programmed cell death regulating tumors and immunity. We constructed a prognostic model based on PANoptosis‐related genes (PRGs) and evaluated its value for predicting immunotherapy response and survival in OC.MethodsPRGs linked to OC prognosis were identified from public databases, followed by using the STRING database to develop a protein–protein interaction (PPI) network. The LASSO and multivariate Cox regression analyses were used to construct a risk model, and its predictive value was verified by survival analysis, receiver operator characteristic (ROC) curve, and nomogram. Next, we analyzed the immune microenvironment by combining CIBERSORT, MCP‐counter, and ssGSEA algorithms and assessed the response of patients in different risk groups to immunotherapy using TIDE with immune phenotype score (IPS) methods. GSEA was performed to evaluate the activation status of biological pathways between patients in different risk groups. Finally, we verified the expression and potential biological functions of the key genes using quantitative reverse transcription‐PCR (qRT‐PCR), CCK‐8, scratch, and transwell assays.ResultsA PANoptosis‐related risk model for OC was constructed based on eight genes (PIK3CG, CAMK2A, CD38, NFKB1, PSMA4, PSMA8, PSMB1, and STAT4). The model could accurately evaluate the prognostic outcomes for OC patients, showing a high stability across different datasets. High‐risk patients had lower immune cell infiltration, elevated TIDE, and reduced IPS, which suggested weaker immunotherapy responsiveness and therefore a worse prognosis. In addition, pathway analysis showed that the high‐risk group was mainly enriched in tumor progression–related pathways. In vitro, PIK3CG, CAMK2A, NFKB1, PSMA4, and PSMB1 were upregulated in OC cell lines, and knockdown of PIK3CG notably suppressed the proliferative, migratory, and invasive capabilities of OC cells.ConclusionThe PRG model established in this study may contribute to the assessment of immunotherapeutic response and prognosis for OC patients.