Prognostic Signatures Based on Ferroptosis- and Immune-Related Genes for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are among the most common malignancies of the female genital tract. Ferroptosis and immunity regulate each other and play important roles in the progression of CESC. The present study aimed to screen ferroptosis- and immune-related differentially expressed genes (FI-DEGs) to identify suitable prognostic signatures for patients with CESC. We downloaded the RNAseq count data and corresponding clinical information of CESC patients from The Cancer Genome Atlas database; obtained recognized ferroptosis- and immune-related genes from the FerrDb and ImmPort databases, respectively; and screened for suitable prognostic signatures using a series of bioinformatics analyses. We identified eight FI-DEGs (CALCRL, CHIT1, DES, DUOX1, FLT1, HELLS, SCD, and SDC1) that were independently correlated with the overall survival of patients with CESC. The prediction model constructed using these eight FI-DEGs was also independently correlated with overall survival. Both the sensitivity and specificity of the prediction model constructed using these eight signatures were over 60%. The comprehensive index of ferroptosis and immune status was significantly correlated with the immunity of patients with CESC. In conclusion, the risk assessment model constructed with these eight FI-DEGs predicted the CESC outcomes. Therefore, these eight FI-DEGs could serve as prognostic signatures for CESC.

Comprehensive Analysis of The Clinical Significance and Prognostic Value of The CBX Family in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC)

Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the second most common type of cancer among gynecologic malignancies worldwide. Chromobox (CBX) family proteins are associated with the regulation of tumorigenesis, metastasis, and evolution of various cancers.Methods: The clinical features, expression levels, and prognostic value of CBXs in CESC were analyzed through several databases, including ONCOMINE, GEPIA, HPA, UALCAN, cBioPortal,Kaplan-Meier plotter and .Results: We concluded that the expression level of CBX2/4/8 was upregulated, while the expression level of CBX6/7 was downregulated in CESC specimens. Immune infiltration analysis revealed that CBX1/2/3/4/5/6/8 proteins were downregulated in normal cervical tissues, and upregulated in CESC specimens. In contrast, CBX7 protein expression was significantly higher in normal adjacent cervical tissues and was not detected in CESC tissues. CBX1/3/6 mRNA expression was significantly correlated with the pathological stage of CESC. Prognostic analysis showed that patients with high CBX7 levels of CESC had a favorable prognosis.Conclusions: Our study indicated that CBX7 could be an attractive biomarker for the prognosis of CESC.

So-Called Serous Carcinoma of the Uterine Cervix with BRCA2 Mutation: Case Report and Review of the Literature

Serous carcinoma of the uterine cervix (SCUC) is now believed to be a morphological variant of an HPV-associated endocervical adenocarcinoma or a metastasis from a serous carcinoma of the upper tract. In terms of mutational status as detected by next-generation sequencing (NGS), this controversial entity has not been characterized yet. We describe the case of a patient with a carcinoma categorized as stage IVB SCUC, initially treated with carboplatin, paclitaxel, and bevacizumab, followed by maintenance with bevacizumab. After locoregional progression, radiotherapy was administered. Unfortunately, further progression was observed, and carboplatin was resumed. Considering the presence of a <i>BRCA2</i> mutation as detected by NGS, treatment with a PARP inhibitor (olaparib) was decided and allowed disease control for 6 months. We believe that <i>BRCA</i> mutation may be systematically searched in patients suffering from carcinomas formerly referred to as SCUC and that targeted treatments should be considered.

HPV E6/E7 mRNA in situ hybridization in endocervical adenocarcinoma: implications for prognosis and diagnosis

Background Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific technique in detecting transcriptionally active HPV. We aimed to examine the diagnostic utility of this technique in endocervical adenocarcinoma (ECA), to explore the prognostic factors for ECA patients and develop a clinically useful nomogram based on clinicopathological parameters to predict it. Methods We retrospectively analyzed 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center from 2010 and 2014. The diagnostic performance of HPV E6/E7 RNAscope were evaluated by receiver operating characteristic (ROC) curve. A prognostic nomogram model including HPV E6/E7 RNAscope was generated based on multivariate Cox regression analysis, then we compared the predictive accuracy of the prognostic model with FIGO staging and treatment using concordance index (C-index), time-dependent ROC (tdROC), and decision curve analysis (DCA). Results The sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non-HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively. According the univariate analysis and multivariate logistic regression analysis, age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope were valuable predictive factors for OS. These parameters were incorporated into the nomogram model (nomogram A) compared with FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825, which was significantly higher than FIGO stage (C-index = 0.653, p = 0.002) and treatment (C-index = 0.578, p < 0.001). Conclusions HPV E6/E7 RNAscope is highly specific for ECA, and the 4-variable nomogram showed more accurate prognostic outcomes in patients with ECA.