RNA-binding proteins signature is a favorable biomarker of prognosis, immunotherapy and chemotherapy response for cervical cancer.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) still present a huge threaten to women's health, especially the local advanced patients. Hence, developing more effectiveness prognostic signatures is urgently needed. This study constructed and verified a robust RNA-binding proteins (RBPs) related signature through a series of bioinformatics methods and explored the biological function of hub RBP in vitro experiments. As a result, the 10 RBPs signature was successfully established and could act as an independent prognostic biomarker in CESC patients, which displayed the highest sensitivity and specificity in prognosis prediction compared with other clinicopathological parameters. The risk model also presented good performance in risk stratification among CESC patients. Besides, a nomogram was constructed based on pathological stage and the risk signature and exhibited satisfactory accuracy in prognosis prediction. Functional enrichment indicated that the risk signature mainly participated in immune-related pathways and cancer-related pathways, and the infiltration level of immune cells and immune checkpoints showed a significantly higher degree in low-risk patients compared with high-risk patients. Notably, the 10 RBPs signature act as a novel biomarker in immunotherapy and chemotherapy response. In addition, PRPF40B was selected as hub RBP and its transcription and translation levels were obviously increased in CESC tissues, as well as Hela and Siha cells. Knockdown of PRPF40B inhibits the proliferation, migration and invasion of Hela and Siha cells in vitro. In conclusion, our research provides a noticeable strategy in prognostic prediction among CESC patients, which may illuminate the prospect of CESC patients' clinical outcome.

Predictive value of protease-activated receptor-2 (PAR2 ) in cervical cancer metastasis.

Metastasis is the primary cause of an unfavourable prognosis in patients with malignant cancer. Over the last decade, the role of proteinases in the tumour microenvironment has attracted increasing attention. As a sensor of proteinases, proteinase-activated receptor 2 (PAR2 ) plays crucial roles in the metastatic progression of cervical cancer. In the present study, the expression of PAR2 in multiple types of cancer was analysed by Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan-Meier plotter was used to calculate the correlation between survival and the levels of PAR2 , Grb-associated binding protein 2(Gab2) and miR-125b. Immunohistochemistry (IHC) was performed to examine PAR2 expression in a tissue microarray (TMA) of CESCs. Empower Stats was used to assess the predictive value of PAR2 in the metastatic potential of CESC. We found that PAR2 up-regulation was observed in multiple types of cancer. Moreover, PAR2 expression was positively correlated with the clinicopathologic characteristics of CESC. miR-125b and its target Gab2, which are strongly associated with PAR2 -induced cell migration, are well-characterized as predictors of the prognostic value of CESC. Most importantly, the Cancer Genome Atlas (TCGA) data set analysis showed that the area under the curve (AUC) of the PAR2 model was significantly greater than that of the traditional model (0.833 vs 0.790, P < .05), demonstrating the predictive value of PAR2 in CESC metastasis. Our results suggest that PAR2 may serve as a prognostic factor for metastasis in CESC patients.

DGUOK-AS1 promotes cervical squamous cell carcinoma progression by suppressing miR-499a-5p that targets SPRR1B in vitro.

PURPOSE: Cervical squamous cell carcinoma (CESC) is the most common cancer type of cervical cancer, which threatens women's life seriously. LncRNA DGUOK-AS1has been reported to promote the biologic processes of CESC. We aim to figure out the role of DGUOK-AS1-miR-499a-5p-SPRR1B axis in modulating the CESC progression in vitro. METHODS: The levels of DGUOK-AS1, miR-499a-5p, and SPRR1B in CESC tissues and cells were examined by RT-qPCR. The interaction of DGUOK-AS1-miR-499a-5p-SPRR1B was verified by luciferase assay. Inhibition of DGUOK-AS1, miR-499a-5p, and SPRR1B was applied for exploring the biological function based on detection of cell viability, proliferation, migration, and apoptosis in CESC SiHa and HeLa cells. RESULTS: DGUOK-AS1 and SPRR1B expressions were obviously elevated, whereas the expression of miR-499a-5p was reduced in both CESC tissues and cells. Silencing of DGUOK-AS1 attenuated cell growth and boosted apoptosis of CESC cells. Notably, DGUOK-AS1 inhibited miR-499a-5p to release SPRR1B, which significantly accelerated the development of CESC. CONCLUSION: DGUOK-AS1sponging miR-499a-5p facilitated CESC cells progression by releasing SPRR1B in vitro. It provides a new sight for the treatment of CESC patients involving DGUOK-AS1-miR-499a-5p-SPRR1B.

Expressions of m6A RNA methylation regulators and their clinical predictive value in cervical squamous cell carcinoma and endometrial adenocarcinoma.

The mortality caused by cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) ranks second among female malignant tumour deaths, but their diagnostic and therapeutic targets are still limited. N6-methyladenosine (m6A) is the most common and extensive modification in mRNA molecules, and its methylation regulators participate in regulating the occurrence and development of many tumours. However, whether m6A RNA methylation regulators can be used as independent prognostic indicators of CESC remains unknown. This study unveiled differential expression of 20 m6A RNA methylation regulators between normal and CESC tumour samples, which RNA sequence data and clinical information were obtained from TCGA database. As a result, five m6A RNA methylation regulators (FTO, HNRNPA2B1, RBM15, IGF2BP1, IGF2BP3) were identified to be significantly linked to CESC tumour status. After Lasso cox regression analysis, six m6A RNA methylation regulators (YTHDC2, YTHDC1, ALKBH5, ZC3H13, RBMX, YTHDF1) were chosen to construct a risk signature. CESC patients were then classified as high-risk and low-risk group based on the median risk score. The overall survival (OS) of the CESC patients in high-risk group was significantly lower than that in low-risk group, and the area under curve (AUC) is 0.718. Moreover, the risk model can be an independent prognosis factors for CESC patients and can predict OS of CESC patients with different clinical factors. In conclusion, m6A RNA methylation regulators are closely correlated with CESC clinical characteristics and the selected six m6A RNA methylation regulators may be useful for CESC patients personalized treatment.

Viability of power distribution in India - Challenges and Way Forward.

Energy is a key component for economic growth as well as for human development. India is the third-ranking electricity generator in the world but ranks 106th in terms of per capita consumption. Specifically, the distribution of power is the most important link in the value chain of the power sector since it is the cash register for the entire sector. In India, electricity is a concurrent subject shared between the Central and State Governments. While the generation of power has been deregulated since 2003, the supply of power to the consumers is generally carried out by Government-owned power Distribution Companies (DISCOMs). In this paper, the authors analyze the financial distress of DISCOMs in India, and explain how the supply-demand mismatch due to over-ambitious demand projections, the fixed and energy charges of thermal power plants, and the excess procurement of "must-run" renewable sources together contribute to the high cost of power procurement that drives the financial stress faced by DISCOMs. The authors support their assertion with a study of nine DISCOMs supplying electricity to 155 million people in three States and propose policy recommendations for a turnaround of such DISCOMs which can be rolled out with suitable modifications across India.

Identification of EPHX2 and RMI2 as two novel key genes in cervical squamous cell carcinoma by an integrated bioinformatic analysis.

Cervical cancer is the fourth most common malignancy in women worldwide and cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer. The dysregulation of genes plays a significant role in cancer. In the present study, we screened out differentially expressed genes (DEGs) of CESC in the GSE63514 data set from the Gene Expression Omnibus database. An integrated bioinformatics analysis was used to select hub genes, as well as to investigate their related prognostic signature, functional annotation, methylation mechanism, and candidate molecular drugs. As a result, a total of 1907 DEGs were identified (944 were upregulated and 963 were downregulated). In the protein-protein interaction network, three hub modules and 30 hub genes were identified. And two hub modules and 116 hub genes were screened out from four CESC-related modules by the weighted gene coexpression network analysis. The gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to better understand functions and pathways. Genes with a significant prognostic value were found by prognostic signature analysis. And there were five genes (EPHX2, CHAF1B, KIAA1524, CDC45, and RMI2) identified as significant CESC-associated genes after expression validation and survival analysis. Among them, EPHX2 and RMI2 were noted as two novel key genes for the CESC-associated methylation and expression. In addition, four candidate small molecule drugs for CESC (camptothecin, resveratrol, vorinostat, and trichostatin A) were defined. Further studies are required to explore these significant CESC-associated genes for their potentiality in diagnosis, prognosis, and targeted therapy.

Standards of care in cauda equina syndrome.

What constitutes cauda equina syndrome (CES), how it should be subclassified and how urgently to image and operate on patients with CES are all matters of debate. A structured review of the literature has led us to evaluate the science and to propose evidence-based guidelines for the management of CES. Our conclusions include this guidance: pain only; MRI negative - recommend: analgesia, ensure imaging complete (not just lumbar spine) adequate follow-up. Bilateral radiculopathy (CESS) with a large central disc prolapse - recommend: discuss with the patient and if for surgery, the next day (unless deteriorates to CESI in which case emergency surgery); CESI - recommend: the true emergency for surgery by day or night; a large central PLID with uncertainty as to whether CESI or CESR (e.g. catheterised prior to CESR) or where there is residual cauda equina nerve root function or early CESR - recommend: treat as an emergency by day or night. Where there has been prolonged CESR and/or no residual sacral nerve root function - recommend: treat on the following day's list.

Identification and Validation of eRNA as a Prognostic Indicator for Cervical Cancer.

The survival of CESC patients is closely related to the expression of enhancer RNA (eRNA). In this work, we downloaded eRNA expression, clinical, and gene expression data from the TCeA and TCGA portals. A total of 7936 differentially expressed eRNAs were discovered by limma analysis, and the relationship between these eRNAs and survival was analyzed by univariate Cox hazard analysis, LASSO regression, and multivariate Cox hazard analysis to obtain an 8-eRNA model. Risk score heat maps, KM curves, ROC analysis, robustness analysis, and nomograms further indicate that this 8-eRNA model is a novel indicator with high prognostic performance independent of clinicopathological classification. The model divided patients into high-risk and low-risk groups, compared pathway diversity between the two groups through GSEA analysis, and provided potential therapeutic agents for high-risk patients.

The effect of TFAP2A/ANXA8 axis on ferroptosis of cervical squamous cell carcinoma (CESC) in vitro.

Potential role and associated mechanisms of Annexin A8 (ANXA8), a member of the Annexins family, in cervical squamous cell carcinoma (CESC) are still unclear, despite being upregulated in various malignant tumors. Here, we observed a notably elevated expression of ANXA8 in CESC cells. The inhibition of ANXA8 amplified the susceptibility of CESC cells to Erastin and sorafenib-induced ferroptosis, whereas it exerted minimal influence on DPI7 and DPI10-induced ferroptosis. The results from the Fe2+ concentration assay showed no significant correlation between ANXA8 gene knockdown and intracellular Fe2+ concentration induced by ferroptosis inducers. Western blot analysis demonstrated that the knockdown of ANXA8 did not alter ACSL4 and LPCAT levels under ferroptosis-inducing conditions, but it did result in a reduction in intracellular GSH levels induced by the ferroptosis inducer. Subsequently, we identified TFAP2A as an upstream transcription factor of ANXA8, which plays a role in regulating cell ferroptosis. The knockdown of TFAP2A significantly elevated MDA levels and depressed GSH levels in the presence of a ferroptosis inducer, thereby inhibiting cell ferroptosis. However, this inhibitory effect could be reversed by ANXA8 overexpression. Therefore, our research suggests that the TFAP2A/ANXA8 axis exerts regulatory control over ferroptosis in CESC cells by mediating GSH synthesis in System Xc.

Decoding the immune landscape: a comprehensive analysis of immune-associated biomarkers in cervical carcinoma and their implications for immunotherapy strategies.

Background and aims: Cervical cancer, a prevalent gynecological malignant tumor, poses a significant threat to women's health and lives. Immune checkpoint inhibitor (ICI) therapy has emerged as a promising avenue for treating cervical cancer. For patients with persistent or recurrent metastatic cervical cancer, If the sequence of dead receptor ligand-1 (PD-L1) is positive, ICI show significant clinical efficacy. PD-L1 expression serves as a valuable biomarker for assessing ICI therapeutic efficacy. However, the complex tumor immune microenvironment (TIME), encompassing immune cell composition and tumor-infiltrating lymphocyte (TIL) status, also exerts a profound influence on tumor immunity and prognosis. Given the remarkable strides made by ICI treatments in improving the survival rates of cervical cancer patients, it becomes essential to identify a comprehensive biomarker that integrates various TIME aspects to enhance the effectiveness of ICI treatment. Therefore, the quest for biomarkers linked to multiple facets of TIME in cervical cancer is a vital pursuit. Methods: In this study, we have developed an Immune-Associated Gene Prognostic Index (IRGPI) with remarkable prognostic value specifically for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). The Cancer Genome Atlas CESC dataset (n = 305) was meticulously analyzed to pinpoint key immune-related genes via weighted gene co-expression network analysis and differential gene expression assays. Subsequently, we employed Cox regression analysis to construct the IRGPI. Furthermore, the composition of immune cells and TIL status were examined using CIBERSORT and TIDE. Tumor expression of Epigen, LCN10, and P73 were determined with immunohistochemistry. Results: The resulting IRGPI, composed of EPGN, LCN10, and TP73 genes, displayed a strong negative correlation with patient survival. The discovery was validated with a patient cohort from our hospital. The IRGPI not only predicts the composition of immune cell subtypes such as Macrophages M1, NK cells, Mast cells, Plasma cells, Neutrophils, Dendritic cells, T cells CD8, and T cells CD4 within CESC, but also indicates TIL exclusion, dysfunction, and PD-1 and PD-L1 expression. Therefore, the IRGPI emerges as a promising biomarker not only for prognostic assessment but also for characterizing multiple immune features in CESC. Additionally, our results underscored the significant associations between the IRGPI and immune cell composition, TIL exclusion, and dysfunction, along with PD-1 and PD-L1 expression in the TIME. Conclusion: Consequently, the IRGPI stands out as a biomarker intimately connected to both the survival and TIME status of CESC patients, offering potential insights into immunotherapy strategies for CESC.

Angiogenesis-related lncRNAs index: A predictor for CESC prognosis, immunotherapy efficacy, and chemosensitivity.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is a common gynecologic tumor and patients with advanced and recurrent disease usually have a poor clinical outcome. Angiogenesis is involved in the biological processes of tumors and can promote tumor growth and invasion. In this paper, we created a signature for predicting prognosis based on angiogenesis-related lncRNAs (ARLs). This provides a prospective direction for enhancing the efficacy of immunotherapy in CESC patients. We screened seven OS-related ARLs by univariate and multivariate regression analyses and Lasso analysis and developed a prognostic signature at the same time. Then, we performed an internal validation in the TCGA-CESC cohort to increase the precision of the study. In addition, we performed a series of analyses based on ARLs, including immune cell infiltration, immune function, immune checkpoint, tumor mutation load, and drug sensitivity analysis. Our created signature based on ARLs can effectively predict the prognosis of CESC patients. To strengthen the prediction accuracy of the signature, we built a nomogram by combining signature and clinical features.

EGLN1: A Biomarker of Poor Prognosis of Cervical Cancer and a Target of Treatment.

Objective: To conduct bioinformatics analysis on the prognostic effect, mechanism of action, and drug sensitivity of Egl-9 family hypoxia-inducible factor 1 (EGLN1) expression on cervical cancer. Methods: Bioinformatics were obtained from Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), and the human cancer metastasis database (HCMDB), and the effect of EGLN1 expression level on the prognosis of cervical cancer was comprehensively analyzed. The protein-protein interaction network was constructed by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and the possible mechanism of EGLN1 affecting the prognosis of cervical cancer was discussed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, Gene Set Cancer Analysis (GSCALite) was used to predict sensitive drugs online. Results: The higher the expression level of EGLN1, the shorter the tumor-free survival time and overall survival time of cervical cancer. The higher the stage of cervical cancer, the higher the expression level of EGLN1. The expression of EGLN1 affects the degree of immune infiltration, the variation of somatic copy number, and the level of N6-methyladenosine (m6A) modification in cervical cancer. COX regression model suggested that EGLN1 was an independent prognostic factor of cervical cancer. Conclusions: The high expression of EGLN1 in cervical cancer is an independent risk factor for the prognosis of cervical cancer, which affects the prognosis of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) through different signal pathways. It is expected to be used to predict the sensitive anticancer drugs for the treatment of cervical cancer.

The Prognostic and Immune Significance of BZW2 in Pan-Cancer and its Relationship with Proliferation and Apoptosis of Cervical Cancer.

BACKGROUND: Basic leucine zipper and W2 domains 2 (BZW2), a member of the basic domain leucine zipper superfamily of transcription factors, has been implicated in the development and progression of various cancers. However, the precise biological role of BZW2 in pan-cancer datasets remains to be explored. This study aimed to assess the prognostic significance of BZW2 and its immune-related signatures in various tumors. METHODS: Our study investigated the expression, epigenetic modifications, and clinical prognostic relevance of BZW2 using multi-omics data in different cancer types. Additionally, the immunological characteristics, tumor stemness, drug sensitivity, and correlation of BZW2 with immunotherapy response were explored. Finally, in vitro experiments were conducted to assess the impact of BZW2 knockdown on Hela cells, a cell line derived from cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). RESULTS: BZW2 exhibited elevated expression levels in various tumor tissues and significantly impacted the prognosis of different cancer types. BZW2 emerged as an independent prognostic factor in CESC. We found that copy number amplification and methylation levels of BZW2 were associated with its mRNA expression. Immunological analyses revealed that BZW2 shapes a non-inflamed immunosuppressive tumor microenvironment across multiple cancers. Furthermore, our cell experiments demonstrated that BZW2 knockdown reduced proliferation, migration, and apoptosis activities in CESC cells. CONCLUSIONS: BZW2 promotes cancer progression by shaping a non-inflamed immunosuppressive tumor microenvironment. Additionally, BZW2 was shown to significantly influence the proliferation, migration, and apoptosis of CESC cells.

Analysis of miR-497/195 cluster identifies new therapeutic targets in cervical cancer.

OBJECTIVE: miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets. RESULTS: In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.

Integrated bioinformatics combined with machine learning to analyze shared biomarkers and pathways in psoriasis and cervical squamous cell carcinoma.

Background: Psoriasis extends beyond its dermatological inflammatory manifestations, encompassing systemic inflammation. Existing studies have indicated a potential risk of cervical cancer among patients with psoriasis, suggesting a potential mechanism of co-morbidity. This study aims to explore the key genes, pathways, and immune cells that may link psoriasis and cervical squamous cell carcinoma (CESC). Methods: The cervical squamous cell carcinoma dataset (GSE63514) was downloaded from the Gene Expression Omnibus (GEO). Two psoriasis-related datasets (GSE13355 and GSE14905) were merged into one comprehensive dataset after removing batch effects. Differentially expressed genes were identified using Limma and co-expression network analysis (WGCNA), and machine learning random forest algorithm (RF) was used to screen the hub genes. We analyzed relevant gene enrichment pathways using GO and KEGG, and immune cell infiltration in psoriasis and CESC samples using CIBERSORT. The miRNA-mRNA and TFs-mRNA regulatory networks were then constructed using Cytoscape, and the biomarkers for psoriasis and CESC were determined. Potential drug targets were obtained from the cMAP database, and biomarker expression levels in hela and psoriatic cell models were quantified by RT-qPCR. Results: In this study, we identified 27 key genes associated with psoriasis and cervical squamous cell carcinoma. NCAPH, UHRF1, CDCA2, CENPN and MELK were identified as hub genes using the Random Forest machine learning algorithm. Chromosome mitotic region segregation, nucleotide binding and DNA methylation are the major enrichment pathways for common DEGs in the mitotic cell cycle. Then we analyzed immune cell infiltration in psoriasis and cervical squamous cell carcinoma samples using CIBERSORT. Meanwhile, we used the cMAP database to identify ten small molecule compounds that interact with the central gene as drug candidates for treatment. By analyzing miRNA-mRNA and TFs-mRNA regulatory networks, we identified three miRNAs and nine transcription factors closely associated with five key genes and validated their expression in external validation datasets and clinical samples. Finally, we examined the diagnostic effects with ROC curves, and performed experimental validation in hela and psoriatic cell models. Conclusions: We identified five biomarkers, NCAPH, UHRF1, CDCA2, CENPN, and MELK, which may play important roles in the common pathogenesis of psoriasis and cervical squamous cell carcinoma, furthermore predict potential therapeutic agents. These findings open up new perspectives for the diagnosis and treatment of psoriasis and squamous cell carcinoma of the cervix.

Exploring Immune-Related Gene Profiling and Infiltration of Immune Cells in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma.

Cervical cancer is a widespread malignancy among women, leading to a substantial global health impact. Despite extensive research, our understanding of the basic molecules and pathogenic processes of cervical squamous cell carcinoma is still insufficient. This investigation aims to uncover immune-related genes linked to CESC and delineate their functions. Leveraging data from the GEO and ImmPort databases, a total of 22 immune-related genes were identified. Multiple tools, including DAVID, the human protein atlas, STRING, GeneMANIA, and TCGA, were employed to delve into the expression and roles of these immune genes in CESC, alongside their connections to the disease's pathological features. Through RT-PCR, the study confirmed notable disparities in CXCL8 and CXCL10 mRNA expression between CESC and normal cervical tissue. The TCGA dataset's immune-related information reinforced the association of CXCL8 and CXCL10 with immune infiltration in CESC. This research sheds light on the potential of CXCL8 and CXCL10 as promising therapeutic targets and essential prognostic factors for individuals diagnosed with CESC.

Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma.

Purpose: To identify new novel biomarkers for predicting the efficacy of concurrent chemoradiotherapy(CCRT) in cervical squamous cell carcinoma(CESC). Methods: Gene expression datasets GSE56363, GSE5787, and GSE168009 were analyzed to identify candidate genes to predict the efficacy of CCRT in CESC. Single-cell RNA sequencing (scRNA-seq) data from GSE168652 and CESC patients in The Cancer Genome Atlas(TCGA) were systematically analyzed to explore possible molecular mechanisms. Kaplan-Meier evaluated the correlation between LUM (Lumican) and prognostic significance. The expression of LUM protein in biopsy tissues before CCRT was detected by immunohistochemistry in 15 CESC patients. Results: LUM mRNA levels were significantly upregulated in nonresponders of CESC.patients receiving CCRT and positively correlated with poor therapeutic effect. Furthermore, high expression of LUM influenced the immune microenvironment in CESC patient-derived organoids treated with CCRT. LUM overexpression in CESC cells induced resistance to CCRT, potentially via immune landscape modulation. Gene Set Enrichment Analysis (GSEA) revealed that possible mechanisms underlying resistance to CCRT might involve the PARs and IL1 signaling pathway affecting the immune landscape. Conclusions: High LUM expression is correlated with poor efficacy in CESC patients receiving CCRT, possibly through the PARs and IL1 signaling pathway affecting the immune landscape.

Prediction of Prognosis and Chemotherapeutic Sensitivity Based on Cuproptosis-Associated lncRNAs in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma.

Cervical cancer is the fourth most common cancer. The 5-year survival rate for metastatic cervical cancer is less than 10%. The survival time of patients with recurrent cervical cancer is approximately 13-17 months. Cuproptosis is a novel type of cell death related to mitochondrial respiration. Accumulative studies showed that long non-coding RNAs (lncRNAs) regulated cervical cancer progression. Compressive bioinformatic analysis showed that nine cuproptosis-related lncRNAs (CRLs), including C002128.2, AC002563.1, AC009237.14, AC048337.1, AC145423.1, AL117336.1, AP001542.3, ATP2A1-AS1, and LINC00426, were independently correlated with the overall survival (OS) of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients. The time-dependent area under curve value reached 0.716 at 1 year, 0.718 at 3 years, and 0.719 at 5 years. Notably, CESC patients in the low-risk group had increased immune cell infiltration and expression of several immune checkpoints, which indicated that they may benefit more from immune checkpoint blockade therapy. In addition, we also used the model for drug sensitivity analysis. Several drug sensitivities were more sensitive in high-risk patients and showed significant correlations with the risk models, such as Bortezomib_1191, Luminespib_1559, and Rapamycin_1084, suggesting that these drugs may be candidate clinical drugs for patients with a high risk of CESC. In summary, this study further explored the mechanism of CRLs in CESC and provided a more optimized prognostic model and some insights into chemotherapy of CESC.

Fatty acid synthase (FASN) inhibits the cervical squamous cell carcinoma (CESC) progression through the Akt/mTOR signaling pathway.

BACKGROUND: Cervical cancer is a malignant tumor that affects females and remains the cause of the highest morbidity and mortality among women worldwide. Currently, gene-targeted therapy is a novel treatment option for clinicians. Furthermore, fatty acid synthase (FASN) plays a therapeutic role in various cancers. Nonetheless, the mechanism of action of this enzyme in cervical squamous cell carcinoma and cervical duct adenocarcinoma (CESC) has not yet been reported. METHODS: RNA (ribonucleic acid) sequencing data and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). The expression levels of FASN were obtained from Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Human Protein Atlas (HPA). Univariate and multivariate Cox regression analyses were utilized to assess independent prognostic factors associated with survival. A nomogram and receiver operating characteristic curve (ROC) were employed to evaluate survival and predictive power. In vitro experiments and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) were conducted to identify cell interference efficiency. MTS, monoclonal formation, and EDU assays were used to determine cell viability. Wound healing and invasion assays (transwell assay) were used to evaluate cell migration and invasion. Finally, Hoechst 33342, propidium iodide (PI) staining and Annexin V-FITC staining were used to assess apoptosis and the cell cycle, while western blotting was utilized to determine the protein expression levels. RESULTS: FASN was aberrantly expressed in various cancers, including CESC, where it was highly expressed. Kaplan-Meier, univariate, multivariate Cox regression analyses and ROC curve indicated that FASN is a potential key indicator of survival prognosis among CESC patients and demonstrated good predictive ability and efficacy. Complementary in vitro experiments confirmed that FASN is an important target for CESC therapy. CONCLUSION: The current study validated the biological and clinical significance of FASN in CESC prognosis, suggesting that FASN knockdown may exert antitumor activity against cervical cancer through the Akt/mTOR signaling pathway.

UCHL1 acts as a prognostic factor and promotes cancer stemness in cervical squamous cell carcinoma.

BACKGROUND: The incidence and death rate of cervical cancer rank fourth among female malignant tumors worldwide. A growing number of researches are devoted to exploring more effective treatment methods and cancer stem cells (CSCs) are thought to be a potential therapeutic target in cervical cancer. In our study, we focused on the expression and function of UCHL1 in cervical squamous cell carcinoma (CESC). METHODS: We detected and the expression of UCHL1 in 134 CESC patients through immunohistochemistry and further confirm UCHL1 was a prognostic factor by univariate and multivariate analysis. Then, according to TCGA database for CESC, we found that UCHL1 expression correlated with the markers associated with CSCs (CD133, ABCG2 and SOX2). Therefore, we used western blot and spheroid formation assays to future evaluate the function of UCHL1 on cancer stemness in C-33A and SiHa cell lines. At the same time, we detected the cell proliferation, migration and invasion change by CCK-8 assay, scratch assay and transwell assay, when UCHL1 was knockdown or overexpressed. Finally, xenograft models were used to examine the effect of UCHL1 in vivo. RESULTS: We found the expression of UCHL1 in mRNA and protein was higher in tumor than in paired normal tissue and was a prognostic factor in CESC. The UCHL1 high expression group showed a shorter survival in the overall survival. According to TCGA database, the expression of UCHL1 was correlated with CD133, ABCG2 and SOX2. The results of sphere-forming ability and CSCs related markers expression were showed UCHL1 promoted cancer stemness in CESC. Similarly, CCK-8 assay, scratch assay and transwell assay were applied to demonstrate that overexpression of UCHL1 promoted the proliferation, migration and invasion in SiHa, but when UCHL1 was knockdown in C-33A, the function of UCHL1 displayed the opposite result. Finally, knockdown UCHL1 inhibited CESC tumor propagation in xenograft models. CONCLUSION: Our results suggest that UCHL1 is a prognostic factor and correlated with cancer stemness, proliferation, migration and invasion of CESC, which may provide a novel therapeutic strategy for CESC treatment.