Identification and validation of the high expression of pseudogene TCAM1P in cervical cancer via integrated bioinformatics analysis.

BACKGROUND: HPV as the main cause of cervical cancer has long been revealed, but the detailed mechanism has not yet been elucidated. The role of testis/cancer antigen in cervical cancer has been revealed. However, there are no reports about the statement of testis/cancer-specific non-coding RNA. In this study, we first proposed TCAM1P as a testis/cancer-specific pseudogene, and used a series of experimental data to verify its relationship with HPV, and analyzed its diagnosis value of high-grade cervical lesions and the mechanism of their high expression in cervical cancer. This provides a new direction for the prevention and treatment of cervical cancer. METHODS: The specific expression of pseudogenes in each tissue was calculated by "TAU" formula. ROC curve was used to judge the diagnosed value of TCAM1P for high-grade lesions. The proliferation ability of cells was measured by CCK8. The expression of TCAM1P, HPV E6/E7 were detected by qRT-PCR. The binding for RBPs on TCAM1P was predicted by starbase v2.0 database, then RIP assay was used to verify. Besides, Gene Ontology (GO) and KEGG enrichment analysis were performed with "clusterprofiler" R package. RESULTS: TCAM1P was specifically high-expressed in normal testicular tissue and cervical cancer. Interesting, with the severity of cervical lesions increased, the expression of TCAM1P increased, and TCAM1P could effectively diagnose high-grade cervical lesions. Besides, the expression of TCAM1P was HPV dependent, with highest expression in HPV-positive cervical cancer tissues. Furthermore, RIP assay showed that EIF4A3 regulated the expression of TCAM1P through binding with it. CCK8 assay showed that TCAM1P promoted the proliferation and the Gene ontology (GO) and KEGG Pathway enrichment analysis same suggested that TCAM1P is involved in multiple ways in cell proliferation including Cell cycle, DNA replication and etc. CONCLUSIONS: In this study, we firstly proposed that TCAM1P is cancer/testis pseudogene and is regulated by HPV E6/E7 and EIF4A3. TCAM1P promotes the proliferation of cervical cancer cells and acts as promoter in cervical cancer. Otherwise, TCAM1P promote proliferation through regulating cell cycle and DNA replication, but more evidence needs to be provided to reveal the mechanism by which TCAM1P plays a role in cervical cancer.

mTORC1 mediates the expansion of hematopoietic stem and progenitor cells through ribosome biogenesis protein Urb2 in zebrafish.

Mammalian target of rapamycin (mTOR) serves as the key sensor to control protein synthesis, cell growth, and survival. Despite mTOR is reported to regulate hematopoietic stem and progenitor cell (HSPC) engraftment and multiple-lineage hematopoiesis in mice, the roles of unique mTOR complexes (mTORCs) in early HSPC development and HSPC pool formation have not been adequately elucidated. Here, we uncover that mTORC1 is essential for early HSPC expansion in zebrafish. mTORC1 signaling was highly activated in definitive HSPCs during the emerging and expanding stages. Pharmacological or genetic inactivation of mTORC1 would cause defective HSPC expansion and migration due to disrupted cell proliferation. Interestingly, mTORC2 is dispensable for early HSPC development. Ribosome biogenesis protein Urb2 was downregulated upon mTORC1 inhibition, and urb2 overexpression partially rescued the hematopoietic defects in mTORC1-deficient embryos. These data demonstrate that mTORC1 signaling regulates early HSPC expansion through Urb2, and this work will deepen our understanding of mTOR in different physiological processes.

Risk factors and assessment of subclinical atherosclerosis in patients with psoriatic arthritis.

OBJECTIVE: To understand the prevalence of subclinical atherosclerosis (SCA) in psoriatic arthritis (PsA) patients; to explore the correlation between PsA combined with SCA and traditional cardiovascular risk factors and disease activity; to compare the role of Framingham Risk Score (FRS) and atherosclerotic cardiovascular disease (ASCVD) scores. METHODS: We included 50 PsA patients who met the CASPAR classification criteria, 50 diabetes patients and 50 healthy people. Clinical data were collected from all patients, minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA), ASCVD, FRS were assessed in patients with PsA, and carotid artery intima-media thickness was measured. RESULTS: The prevalence of SCA in PsA patients was significantly higher than that in healthy controls (44% vs 24%, P<0.05). Smoking, drinking, ASCVD, FRS were the risk factors of PsA with SCA (P<0.05). Psoriasis (PsO) duration, PtGA, VAS and DAPSA were the risk factors for PsA with SCA (P<0.05). FRS and ASCVD scores underestimated SCA risk in PsA patients. CONCLUSION: Compared with healthy controls, patients with PsA have higher prevalence of SCA. High DAPSA is a risk factor for PsA with SCA. Carotid ultrasound can monitor SCA in patients with PsA, improve stratification of cardiovascular risk.

High-fat diet promotes tumor growth in the patient-derived orthotopic xenograft (PDOX) mouse model of ER positive endometrial cancer.

Endometrial cancer, one of the common gynecological malignancies, is affected by several influencing factors. This study established a unique patient-derived orthotopic xenograft (PDOX) nude mouse model for the study of influencing factors in ER positive endometrial cancer. The aim of this study was to demonstrate that a high-fat diet can affect the growth of ER positive endometrial cancer PDOX model tumors. The tumor tissues were expanded by subcutaneous transplantation in nude mice, and then the subcutaneous tumor tissues were orthotopically implanted into the nude mouse uterus to establish the PDOX model. After modeling, they were divided into high-fat diet group and normal diet group for 8 weeks of feeding, which showed that high-fat diet significantly promoted tumor growth (P < 0.001) and increased the protein expression level of ERα in tumor tissues. This study demonstrates that PDOX models of endometrial cancer can embody the role of dietary influences on tumor growth and that this model has the potential for preclinical studies of cancer promoting factors.

Carbonic anhydrase 10 functions as a tumor suppressor in renal cell carcinoma and its methylation is a risk factor for survival outcome.

Carbonic anhydrase 10 (CA10), one of the carbonic anhydrase isozymes, is explored to be downregulated in several tumor types, which indicates its critical role in tumorigenesis. However, its biologic and pathological function remains elusive in the pathogenesis of renal cell carcinoma (RCC). We examined expressions and functions of CA10 in RCC primary tumors and cell lines, assessed its tumor suppressive functions and further explored its impact on survival outcome of RCC patients. We found that CA10 was down-expressed in RCC primary tumors compared with adjacent non-malignant renal tissues. Promoter CpG methylation seemed to directly suppress the transcription of CA10 in RCC cells, which could be reversed by demethylation treatment. Restoration of CA10 in 786-O and Caki-2 cell lines inhibited their cell proliferation and promoted their apoptosis by regulating relevant apoptosis factors. Kaplan-Meier curve identified that CA10 methylation status was associated with progression-free survival in RCC (P = 0.021). Multivariate Cox regression analyses indicated the CA10 methylation status [HR, 4.724; 95% CI, 1.056-21.136; P = 0.042] was an independent predictor of disease progression. Collectively, our study demonstrates that CA10 as a tumor suppressor is frequently inactivated by promoter CpG methylation in RCC and its methylation is a risk factor for the prognosis of RCC.

The comprehensive complication index is more sensitive than the Clavien-Dindo classification for grading complications in elderly patients after radical cystectomy and pelvic lymph node dissection: Implementing the European Association of Urology guideline.

Objectives: Lack of assessment of 90-d perioperative morbidity in elderly patients after radical cystectomy and pelvic lymph node dissection (PLND) using a standard reporting methodology, and the Clavien-Dindo classification (CDC) does not accurately reflect the burden of complications. We aim to report the 90-d complications of elderly patients after radical cystectomy, and to compare the validity of the Comprehensive Complication Index (CCI) and CDC. Methods: Retrospective review of 280 patients aged ≥75 years who received radical cystectomy between 2006 and 2021. The 90-d complications of elderly patients after radical cystectomy were reported by implementing the EAU criteria. The CDC and CCI were both used for grading complications. The Spearman rank correlation coefficient was used to estimate the correlation between postoperative stay and CDC/CCI. Logistic regression was used to identify the risk factors for major complications. The sample size for a fictive superiority trial was calculated for different endpoints. Results: A total of 225 (80.36%) patients suffered from 528 complications. The cumulative CCI had a more accurate prediction of postoperative stay than the CDC (r = 0.378, p < 0.001 vs. r = 0.349, p < 0.001). The need for sample size could decrease when CCI was used for the primary endpoint. More risk factors for major complications were identified when CCI ≥33.7 was defined as the endpoint of major complications. Conclusion: CCI is better than CDC for grading the severity of complications in elderly patients after radical cystectomy and PLND.

Pyroptosis-Related Gene Signature Predicts the Prognosis of ccRCC Using TCGA and Single-Cell RNA Seq Database.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of renal carcinoma, which is not sensitive to both radiotherapy and chemotherapy. The objective response rate of metastatic renal cancer to targeted drugs and immunotherapy is unsatisfactory. Pyroptosis, proven as an inflammatory form of programmed cell death, could be activated by some inflammasomes, while could create a tumor-suppressing environment by releasing inflammatory factors in the tumor. To explore indicators predicting the prognosis of ccRCC and the effect of antitumor therapy, we constructed a pyroptosis risk model containing 4 genes after 11 pyroptosis-related genes of 516 ccRCC cases in the TCGA database were scanned. Based on the risk score, 516 ccRCC cases were divided into two groups for functional enrichment analysis and immune profile to seek functional pathways and potential therapeutic targets. Besides, those results were verified in GSE29609 and single-cell transcriptomic data. The study suggests that the conducted pyroptosis model could predict the prognosis of ccRCC and reflect the immune microenvironment, which may help in immune checkpoint inhibitor treatment.

Head-to-Head Comparison of the Expression Differences of NECTIN-4, TROP-2, and HER2 in Urothelial Carcinoma and Its Histologic Variants.

Background: Antibody-drug conjugates (ADC), such as enfortumab vedotin (EV), sacituzumab govitecan (SG), and RC-48, have shown outstanding response rates to local advanced or metastatic urothelial carcinoma (UC). However, their corresponding target expression characteristics in UC and its histologic variants were unknown. Methods: We detected the expression of NECTIN-4, TROP-2, and HER2, which are the corresponding targets of ADCs EV, SG, and RC-48 in muscle-invasive UC through immunohistochemistry. Results: 161 consecutive samples from 2017 to 2021 of muscle-invasive UC and its histologic variants were obtained in Peking University First Hospital. Variant histology types included 72UC, 10 squamous carcinomas, 23 glandular carcinomas, 19 small cell carcinomas, 19 micropapillary variants, and 18 nested variants. NECTIN-4 expression was found to be 57/72 (79.2%), 10/10 (100%), 15/23 (65.2%), 4/19 (21.1%), 15/19 (78.9%), and 16/18 (88.9%) in conventional UC, squamous carcinoma, glandular carcinoma, small cell carcinoma, micropapillary, and nested variant, respectively, compared with 65/72 (90.3%), 8/10 (80.0%), 13/23 (56.5%), 3/19 (15.8%), 16/19 (84.2%), and 15/18 (83.3%) of TROP-2, and 26/72 (36.1%), 0, 5/23 (21.7%), 6/19 (31.6%), 5/19 (26.3%), and 7/18 (38.9%) of HER2.

PARP inhibitor resistance in breast and gynecological cancer: Resistance mechanisms and combination therapy strategies.

Breast cancer and gynecological tumors seriously endanger women's physical and mental health, fertility, and quality of life. Due to standardized surgical treatment, chemotherapy, and radiotherapy, the prognosis and overall survival of cancer patients have improved compared to earlier, but the management of advanced disease still faces great challenges. Recently, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) have been clinically approved for breast and gynecological cancer patients, significantly improving their quality of life, especially of patients with BRCA1/2 mutations. However, drug resistance faced by PARPi therapy has hindered its clinical promotion. Therefore, developing new drug strategies to resensitize cancers affecting women to PARPi therapy is the direction of our future research. Currently, the effects of PARPi in combination with other drugs to overcome drug resistance are being studied. In this article, we review the mechanisms of PARPi resistance and summarize the current combination of clinical trials that can improve its resistance, with a view to identify the best clinical treatment to save the lives of patients.

EphA2 Promotes the Development of Cervical Cancer through the CXCL11/PD-L1 Pathway.

Erythropoietin-producing hepatoma receptor A2 (EphA2), receptor tyrosine kinase, the most widespread member of the largest receptor tyrosine kinase family, plays a critical role in physiological and pathological conditions. In recent years, the role of EphA2 in the occurrence and development of cancer has become a research hotspot and is considered a promising potential target. Our previous studies have shown that EphA2 has an indisputable cancer-promoting role in cervical cancer, but its related mechanism requires further research. In this study, high-throughput sequencing was performed on EphA2 knockdown cervical cancer cells and the control group. An analysis of differentially expressed genes revealed that EphA2 may exert its cancer-promoting effect through C-X-C motif chemokine ligand 11 (CXCL11). In addition, we found that EphA2 could further regulate programmed cell death ligand 1 (PD-L1) through CXCL11. This has also been further demonstrated in in vivo experiments. Our study demonstrated that EphA2 plays a tumor-promoting role in cervical carcinoma through the CXCL11/PD-L1 pathway, providing new guidance for the targeted therapy and combination therapy of cervical carcinoma.

Praja2 suppresses the growth of gastric cancer by ubiquitylation of KSR1 and inhibiting MEK-ERK signal pathways.

Gastric cancer (GC) is a common malignant tumor, which has a high incidence and fatality. Therefore, it is important to clarify the molecular mechanism of the occurrence and development for GC and to find more effective treatments and targeted drugs. In this study, we found that the kinase suppressor of Ras1 (KSR1) was increased in GC tissues and cell lines. Silencing of KSR1 inhibited the proliferation, migration and invasion of MKN-45 cells. E3 ligase Praja2 was downregulated in GC tissues and cell lines. In addition, praja2 promoted ubiquitylation of KSR1, but inhibited MEK-ERK signal pathways. Functional analysis indicated overexpression of praja2 inhibited the proliferation, migration and invasion of MKN-45 cells, while MG132 or FGF2 treatment removed the inhibitory effects of praja2 on GC progression. In vivo tumorigenesis experiments indicated praja2 inhibited tumor growth via KSR1-MEK-ERK axis. In conclusion, praja2 promoted the ubiquitylation and degradation of KSR1, which disturbed MEK- ERK signaling and inhibited GC progression. Our study might provide a novel target for GC clinical treatment.

Identifying Hypoxia Characteristics to Stratify Prognosis and Assess the Tumor Immune Microenvironment in Renal Cell Carcinoma.

Background: Renal cell carcinoma (RCC) is a common malignant tumor worldwide, and immune checkpoint inhibitors are a new therapeutic option for metastatic RCC. Infiltrating immune cells in the tumor microenvironment (TME) play a critical part in RCC biology, which is important for tumor therapy and prediction. Hypoxia is a common condition that occurs in the TME and may lead to RCC immunosuppression and immune escape. This study was conducted to analyze the extent of the hypoxia immune microenvironment in the TME of RCC and develop a hypoxia-related risk model for predicting the prognosis of patients with RCC. Methods: The gene expression profiles of 526 patients with RCC were downloaded from The Cancer Genome Atlas database. Combined with the hallmark-hypoxia gene dataset downloaded from Gene Set Enrichment Analysis, prognosis-related hypoxia genes were selected by survival analysis. A protein-protein interaction network and functional enrichment analysis were performed. A hypoxia-related risk model predicting the prognosis of patients with RCC was established using the least absolute shrinkage and selection operator. Data of 91 cases downloaded from the International Cancer Genome Consortium (ICGC) database were used for validation. CIBERSORT was applied to analyze the fractions of 22 immune cell types in the TME of RCC between low- and high-risk groups. The expression profiles of immunomodulators and immunosuppressive cytokines were also analyzed. Results: Ninety-three genes were significantly associated with poor overall survival of patients with RCC and were mainly involved in 10 pathways. Using the established hypoxia-related risk model, the receiver operating characteristic curves showed an accuracy of 76.1% (95% CI: 0.719-0.804), and Cox proportional hazards regression analysis revealed that the model was an independent predictor of the prognosis of patients with RCC [hazard ratio (HR) = 2.884; 95% CI: 2.090-3.979] (p < 0.001). Using the ICGC database, we verified that the low-risk score group had a better overall survival outcome than the high-risk group. Additionally, dividing the hypoxia risk score into high-risk and low-risk groups could predict the immune microenvironment of RCC. Conclusions: We demonstrated that a hypoxia-related risk model can be used to predict the outcomes of patients with RCC and reflect the immune microenvironment of RCC, which may help improve the overall clinical response to immune checkpoint inhibitors.

Identifying a hypoxia related score to predict the prognosis of bladder cancer: a study with The Cancer Genome Atlas (TCGA) database.

BACKGROUND: Recurrence is common in bladder cancer, with a hypoxic tumor microenvironment (TME) playing a role in genetic instability and prognosis of bladder cancer. However, we still lack practical hypoxia related model for predicting the prognosis of bladder cancer. In this study, we identified new prognosis-related hypoxia genes and established a new hypoxia score related signature. METHODS: The Gene Set Variation Analysis (GSVA) algorithm was utilized to calculate the hypoxia score of bladder cancer cases found on the The Cancer Genome Atlas (TCGA) database on the gene expression profiles. The cases were first divided into low- and high-hypoxia score groups and then differentially expressed genes (DEGs) expression analysis was conducted. Hypoxia-related genes were identified using weighted gene co-expression network analysis (WGCNA). We then conducted a protein-protein interaction (PPI) network and carried out functional enrichment analysis of the genes that overlapped between DEGs and hypoxia-related genes. LASSO Cox regression analysis was used to establish a hypoxia-related prognostic signature, which was validated using the GSE69795 dataset downloaded from GEO database. RESULTS: Results from Kaplan-Meier analysis showed that patients with a high hypoxia score had significantly poor overall survival compared to patients with low hypoxia score. We selected 270 DEGs between low- and high-hypoxia score groups, while WGCNA analysis identified 1,313 genes as hypoxia-related genes. A total of 170 genes overlapped between DEGs and hypoxia-related genes. LASSO algorithms identified 29 genes associated with bladder cancer prognosis, which were used to construct a novel 29-gene signature model. The prognostic risk model performed well, since the receiver operating characteristic (ROC) curve showed an accuracy of 0.802 (95% CI: 0.759-0.844), and Cox proportional hazards regression analysis proved the model an independent predictor with hazard ratio (HR) =1.789 (95% CI: 1.585-2.019) (P<0.001). The low-risk score patients had remarkably longer overall survival than patients with a higher score (survival rate 71.06% vs. 23.66%) in the The Cancer Genome Atlas (TCGA) cohort (P<0.0001) and in the dataset GSE69795 (P=0.0079). CONCLUSIONS: We established a novel 29-gene hypoxia-related signature model to predict the prognosis of bladder cancer cases. This model and identified hypoxia-related genes may further been used as biomarkers, assisting the evaluation of prognosis of bladder cancer cases and decision making in clinical practice.

m6A-mRNA Methylation Regulates Gene Expression and Programmable m6A Modification of Cellular RNAs With CRISPR-Cas13b in Renal Cell Carcinoma.

Background: N6-methyladenosine (m6A) is the most extensive messenger RNA modification. Despite recent advances in the biological roles of m6A, its role in the development and progression of renal cell carcinoma (RCC) remains unclear. Methods: In this study, we gained the transcriptome-wide m6A profile and gene expression pattern in RCC and paired adjacent peritumoral tissues by meRIP-seq and RNA-seq. m6A modifications of mRNAs were validated by meRIP-qPCR in tissues, and targeted methylation or demethylation was validated by using a CRISPR-Cas13b-based tool in RCC cell lines. Results: Our findings showed that there were 13,805 m6A peaks among 5,568 coding gene transcripts (mRNAs) in adjacent tissues and 24,730 m6A peaks among 6,866 mRNAs in tumor tissues. Furthermore, m6A modification sites were usually located in the coding sequences (CDS), and some near the start and stop codons. Gene Ontology analysis revealed that coding genes had differential N6-methyladenosine sites and were enriched in kidney development and cancer-related signaling pathways. We also found that different levels of m6A modifications could regulate gene expression. Conclusion: In summary, our results provided evidence for studying the potential function of RNA m6A modification and m6A-mediated gene expression regulation in human RCC.

Fangchinoline exerts antitumour activity by suppressing the EGFR­PI3K/AKT signalling pathway in colon adenocarcinoma.

Fangchinoline (FAN), an alkaloid extracted from Stephania tetrandra, has a variety of biological and pharmacological activities, but evidence of its effects on colon adenocarcinoma (COAD) is limited. Therefore, the present study aimed to elucidate the molecular mechanisms by which FAN affects COAD. The cytotoxicity, viability and proliferation of DLD­1 and LoVo cells were assessed in the presence of FAN using MTT and colony formation assays. The effects of FAN on apoptosis and the cell cycle in COAD cells were analysed by flow cytometry, and the migration and invasion of these cells were assessed by wound healing and Transwell experiments. Furthermore, a network pharmacological analysis was conducted to investigate the target of FAN and the results were confirmed by western blotting. In addition, a xenograft model was established in nude mice, and ultrasound imaging was used to assess the preclinical therapeutic effects of FAN in vivo. To the best of our knowledge, the results of this study provided the first evidence that FAN inhibited cellular proliferation, stemness, migration, invasion, angiogenesis and epithelial­mesenchymal transition (EMT), and induced apoptosis and G1­phase cell cycle arrest. Network pharmacological analysis further confirmed that FAN prevented EMT through the epidermal growth factor receptor (EGFR)­phosphoinositide 3­kinase (PI3K)/AKT signalling pathway. Finally, FAN significantly repressed tumour growth and promoted apoptosis in xenografts. Thus, targeting EGFR with FAN may offer a novel therapeutic approach for COAD.

Renal Ewing's sarcoma/primitive neuroectodermal tumor (PNET): a case series of 7 patients and literature review.

BACKGROUND: Primitive neuroectodermal tumor (PNET) is a rare kind of sarcoma that is primarily found in the kidney and has a very poor prognosis. Here, we review and summarize the clinical data of patients with renal PNET in our center and follow up the patients for survival status. Although the current literature suggests that chemotherapy may benefit the survival of these patients, the information from our center suggests that this may not be the case. METHODS: We retrospectively analyzed the clinical data of patients with renal PNET diagnosed pathologically at Peking University First Hospital from January 1, 2007, to January 1, 2018. All of the patients were followed up for survival status. RESULTS: Seven patients with renal PNET were found. The ratio of males to females was 6:1. The median age was 29 years (21-72 years) at the time of diagnosis. The preoperative imaging examination showed a large renal mass protruding outwards from the renal contour, with internal necrosis and hemorrhage. Six/7 patients were diagnosed with distant metastasis or retroperitoneal lymph node metastasis. The main clinical manifestations of patients were pain (5/7) and fever (3/7). In immunohistochemistry, all patients' samples were CD99 positive. All patients died in our follow-up, with an average overall survival (OS) of 12.09 months (1.90-26.77 months). CONCLUSIONS: As a rare renal tumor, renal PNET has a propensity to occur in young males. Most patients have distant metastasis when they are diagnosed, and the prognosis is very poor. Effective treatments are urgently needed.

A Risk Score Model Incorporating Three m6A RNA Methylation Regulators and a Related Network of miRNAs-m6A Regulators-m6A Target Genes to Predict the Prognosis of Patients With Ovarian Cancer.

Ovarian cancer (OC) is the leading cause of cancer-related death among all gynecological tumors. N6-methyladenosine (m6A)-related regulators play essential roles in various tumors, including OC. However, the expression of m6A RNA methylation regulators and the related regulatory network in OC and their correlations with prognosis remain largely unknown. In the current study, we obtained the genome datasets of OC from GDC and GTEx database and analyzed the mRNA levels of 21 key m6A regulators in OC and normal human ovarian tissues. The expression levels of 7 m6A regulators were lower in both the OC tissues and the high-stage group. Notably, the 5-year survival rate of patients with OC presenting low VIRMA expression or high HNRNPA2B1 expression was higher than that of the controls. Next, a risk score model based on the three selected m6A regulators (VIRMA, IGF2BP1, and HNRNPA2B1) was built by performing a LASSO regression analysis, and the moderate accuracy of the risk score model to predict the prognosis of patients with OC was examined by performing ROC curve, nomogram, and univariate and multivariate Cox regression analyses. In addition, a regulatory network of miRNAs-m6A regulators-m6A target genes, including 2 miRNAs, 3 m6A regulators, and 47 mRNAs, was constructed, and one of the pathways, namely, miR-196b-5p-IGF2BP1-PTEN, was initially validated based on bioinformatic analysis and assay verification. These results demonstrated that the risk score model composed of three m6A RNA methylation regulators and the related network of miRNAs-m6A regulators-m6A target genes is valuable for predicting the prognosis of patients with OC, and these molecules may serve as potential biomarkers or therapeutic targets in the future.

Epigenetic Alterations in Renal Cell Cancer With TKIs Resistance: From Mechanisms to Clinical Applications.

The appearance of tyrosine kinase inhibitors (TKIs) has been a major breakthrough in renal cell carcinoma (RCC) therapy. Unfortunately, a portion of patients with TKIs resistance experience disease progression after TKIs therapy. Epigenetic alterations play an important role in the development of TKIs resistance. Current evidence suggests that epigenetic alterations occur frequently in RCC patients with poor response to TKIs therapy, and modulation of them could enhance the cytotoxic effect of antitumor therapy. In this review, we summarize the currently known epigenetic alterations relating to TKIs resistance in RCC, focusing on DNA methylation, non-coding RNAs (ncRNAs), histone modifications, and their interactions with TKIs treatment. In addition, we discuss application of epigenetic alteration analyses in the clinical setting to predict prognosis of patients with TKIs treatment, and the potential use of epigenetics-based therapies to surmount TKIs resistance.

Surgical management of angiomyolipoma with vena cava thrombus during pregnancy: a case report.

Renal angiomyolipoma (AML) can grow and worsen during pregnancy. Sporadic classic variant renal AML with tumor thrombus in the renal vein and inferior vena cava (IVC) during pregnancy is rare. We report a case of complex surgical treatment during pregnancy with normal childbirth. A 27-year-old woman with bilateral AML was faced with large asymptomatic AML and IVC thrombus at 24 weeks of gestation. The magnetic resonance imaging showed that the tumor thrombus had fatty signal. The tumor and IVC thrombus were treated by laparoscopic nephrectomy and open tumor thrombectomy during pregnancy. The patient underwent term spontaneous vaginal delivery at 39 weeks of gestation smoothly and the neonate was in good health. Successful retroperitoneal laparoscopic nephrectomy with open tumor thrombectomy during pregnancy is possible in dealing with invasive renal AML for pregnant patients. Renal AML requires close follow-up during pregnancy. And detailed consult with urologists is necessary before pregnancy.