SMYD4 monomethylates PRMT5 and forms a positive feedback loop to promote hepatocellular carcinoma progression.

Both lysine and arginine methyltransferases are thought to be promising therapeutic targets for malignant tumors, yet how these methyltransferases function in malignant tumors, especially hepatocellular carcinoma (HCC), has not been fully elucidated. Here, we reported that SMYD4, a lysine methyltransferase, acts as an oncogene in HCC. SMYD4 was highly upregulated in HCC and promoted HCC cell proliferation and metastasis. Mechanistically, PRMT5, a well-known arginine methyltransferase, was identified as a SMYD4-binding protein. SMYD4 monomethylated PRMT5 and enhanced the interaction between PRMT5 and MEP50, thereby promoting the symmetrical dimethylation of H3R2 and H4R3 on the PRMT5 target gene promoter and subsequently activating DVL3 expression and inhibiting expression of E-cadherin, RBL2, and miR-29b-1-5p. Moreover, miR-29b-1-5p was found to inversely regulate SMYD4 expression in HCC cells, thus forming a positive feedback loop. Furthermore, we found that the oncogenic effect of SMYD4 could be effectively suppressed by PRMT5 inhibitor in vitro and in vivo. Clinically, high coexpression of SMYD4 and PRMT5 was associated with poor prognosis of HCC patients. In summary, our study provides a model of crosstalk between lysine and arginine methyltransferases in HCC and highlights the SMYD4-PRMT5 axis as a potential therapeutic target for the treatment of HCC.

Circular RNA circARHGEF28 inhibited the progression of prostate cancer via the miR-671-5p/LGALS3BP/NF-κB axis.

Circular RNAs (circRNAs) play crucial roles in various biological processes, including prostate cancer (PCa). However, the precise roles and mechanism of circRNAs are complicated. Hence, we studied the function of a circRNA that might be involved in the progression of PCa. In this study, we found that circARHGEF28 was frequently downregulated in PCa tissues and cell lines. Furthermore, gain- and loss-of function experiments in vitro showed that circARHGEF28 inhibited proliferation, migration, and invasion of PCa. Additionally, circARHGEF28 suppressed PCa progression in vivo. Bioinformatics analysis and RNA pull-down and capture assay found that circARHGEF28 sponged miR-671-5p in PCa cells. Importantly, qRT-PCR and dual luciferase assays found that Lectin galactoside-binding soluble 3 binding protein (LGALS3BP) was downstream of miR-671-5p, and western blot analysis further confirmed that LGALS3BP negatively regulated the nuclear factor kappa-B (NF-κB) pathway. These results demonstrated that circARHGEF28 abolished the degradation of LGALS3BP by sponging miR-671-5p, thus blocking the activation of the NF-κB pathway. Our findings revealed that circARHGEF28/miR-671-5p/LGALS3BP/NF-κB may be an important axis that regulates PCa progression.

Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer.

BACKGROUND: The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. METHODS: We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. RESULTS: We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. CONCLUSIONS: Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC.

Mechanism of prognostic marker SPOCK3 affecting malignant progression of prostate cancer and construction of prognostic model.

BACKGROUND: SPOCK3 is a secreted extracellular matrix proteoglycan. This study aimed to investigate the effect of SPOCK3 on the malignant progression of prostate cancer and to construct a prognostic model to predict DFS of patients with prostate cancer. METHODS: Clinical and transcriptome sequencing data for prostate cancer were download from the TCGA and GEO databases. The survival curve showed that SPOCK3 has prognostic significance. GO, KEGG, and GSEA enrichment analysis were used to investigate how SPOCK3 affects the malignant progression of prostate cancer. Based on ESTIMATE and ssGSEA, the relationship between SPOCK3 and immune cell infiltration in prostate cancer tissue was clarified. Univariate and multivariate COX regression analysis was used to identify the independent prognostic factors of prostate cancer OS and to construct a nomogram. The calibration curve and ROC curves were drawn to assess the nomogram's predictive power. RESULTS: The survival curve revealed that patients in the low-expression group of SPOCK3 had a poor prognosis. According to enrichment analysis, SOPCK3-related genes were enriched in collagen-containing extracellular matrix, PI3K-Akt, and MAPK signaling pathway. ESTIMATE analysis revealed that SPOCK3 expression was positively correlated with the interstitial score, immune score, and ESTIMATE score. The results of ssGSEA analysis revealed that the infiltration levels of Mast cells, NK cells, and B cells were higher in the SPOCK3 high expression group. Cox regression analysis showed that SPOCK3 expression level, T and Gleason score were independent risk factors of patient prognosis, and a nomogram was constructed. The ROC curve showed the AUCs of DFS at 2, 3, and 5 years. CONCLUSION: SPOCK3 is a protective factor for DFS in prostate cancer patients. SPOCK3 is significantly associated with immune cell infiltration. The prognostic model constructed based on SPOCK3 has excellent predictive performance.

circRIP2 accelerates bladder cancer progression via miR-1305/Tgf-ß2/smad3 pathway.

BACKGROUND: Increasing evidences indicate that circular RNAs exert critical function in regulating bladder cancer progression. However, the expressive patterns and roles of circular RNAs in bladder cancer remain less investigated. METHODS: circRIP2 was identified and evaluated by RNA-sequencing and qPCR; in vitro effects of circRIP2 were determined by CCK8, clone forming, wound healing and trans-well assays; while mice subcutaneous tumor model was designed for in vivo analysis. Western blot, RNA pulldown assay, miRNA capture and dual luciferase assessment were applied for mechanistic studies. RESULTS: circRIP2 was identified as a conserved and dramatically repressed circular RNA in bladder cancer. Patients that displayed higher circRIP2 expression negatively associate with the grade, stage, metastasis as well as outcome of bladder cancer. In vitro and in vivo studies suggest that circRIP2 enables to promote bladder cancer progression via inducing EMT. Regarding the mechanism, we performed RNA-sequencing analysis, RNA pulldown with biotin-labeled circRIP2-specific probe, dual luciferase reporter assay. It was found that circRIP2 enables to sponge miR-1305 to elevate Tgf-ß2 in bladder cancer, and inducing EMT via Tgf-ß2/smad3 pathway. Blocking Tgf-ß2 in bladder cancer deprives circRIP2 induced cancer progression and EMT. CONCLUSIONS: Taken together, our study provides the first evidence that circRIP2 expresses differentially in bladder cancer and negatively along with the cancer progression; effective circRIP2 activity accelerates bladder cancer progression via inducing EMT by activating miR-1305/Tgf-ß2/smad3 pathway. The research implies that circRIP2 might be a potential biomarker and therapeutic target for bladder cancer patients.

Correction to: Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis.

An amendment to this paper has been published and can be accessed via the original article.

Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis.

BACKGROUND: Increasing evidence has revealed that circular RNAs (circRNAs) play crucial roles in cancer biology. However, the role and underlying regulatory mechanisms of circFNDC3B in bladder cancer (BC) remain unknown. METHODS: A cell invasion model was established by repeated transwell assays, and invasion-related circRNAs in BC were identified through an invasion model. The expression of circFNDC3B was detected in 82 BC tissues and cell lines by quantitative real-time PCR. Functional assays were performed to evaluate the effects of circFNDC3B on proliferation, migration and invasion in vitro-, and on tumorigenesis and metastasis in vivo. The relationship between circFNDC3B and miR-1178-3p was confirmed by fluorescence in situ hybridization, pull-down assay and luciferase reporter assay. RESULTS: In the present study, we identified a novel circRNA (circFNDC3B) through our established BC cell invasion model. We found that circFNDC3B was dramatically downregulated in BC tissues and correlated with pathological T stage, grade, lymphatic invasion and patients' overall survival rate. Functionally, overexpression of circFNDC3B significantly inhibited proliferation, migration and invasion both in vitro and in vivo. Mechanistically, circFNDC3B could directly bind to miR-1178-3p, which targeted the 5'UTR of the oncogene G3BP2. Moreover, circFNDC3B acted as a miR-1178-3p sponge to suppress G3BP2, thereby inhibiting the downstream SRC/FAK signaling pathway. CONCLUSIONS: CircFNDC3B may serve as a novel tumor suppressive factor and potential target for new therapies in human BC.

Single-cell analysis extracted CAFs-related genes to established online app to predict clinical outcome and radiotherapy prognosis of prostate cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a significant role in regulating the clinical outcome and radiotherapy prognosis of prostate cancer (PCa). The aim of this study is to identify CAFs-related genes (CAFsRGs) using single-cell analysis and evaluate their potential for predicting the prognosis and radiotherapy prognosis in PCa. METHODS: We acquire transcriptome and single-cell RNA sequencing (scRNA-seq) results of PCa and normal adjacent tissues from The GEO and TCGA databases. The "MCPcounter" and "EPIC" R packages were used to assess the infiltration level of CAFs and examine their correlation with PCa prognosis. ScRNA-seq and differential gene expression analyses were used to extract CAFsRGs. We also applied COX and LASSO analysis to further construct a risk score (CAFsRS) to assess biochemical recurrence-free survival (BRFS) and radiotherapy prognosis of PCa. The predictive efficacy of CAFsRS was evaluated by ROC curves and subgroup analysis. Finally, we integrated the CAFsRS gene signature with relevant clinical features to develop a nomogram, enhancing the predictive accuracy. RESULTS: The abundance of CAFs is associated with a poor prognosis of PCa patients. ScRNA-seq and differential gene expression analysis revealed 323 CAFsRGs. After COX and LASSO analysis, we obtained seven CAFsRGs with prognostic significance (PTGS2, FKBP10, ENG, CDH11, COL5A1, COL5A2, and SRD5A2). Additionally, we established a risk score model based on the training set (n = 257). The ROC curve was used to confirm the performance of CAFsRS (The AUC values for 1, 3 and 5-year survival were determined to be 0.732, 0.773, and 0.775, respectively.). The testing set (n = 129), GSE70770 set (n = 199) and GSE116918 set (n = 248) revealed that the model exhibited exceptional predictive performance. This was also confirmed by clinical subgroup analysis. The violin plot demonstrated a statistically significant disparity in the CAFs infiltrations between the high-risk and low-risk groups of CAFsRS. Further analysis confirmed that both CAFsRS and T stage were independent prognostic factors for PCa. The nomogram was then established and its excellent predictive performance was demonstrated through calibration and ROC curves. Finally, we developed an online prognostic prediction app ( https://sysu-symh-cafsnomogram.streamlit.app/ ) to facilitate the practical application of the nomogram. CONCLUSIONS: The prognostic prediction risk score model we constructed could accurately predict BRFS and radiotherapy prognosis PCa, which can provide new ideas for clinicians to develop personalized PCa treatment and follow-up programs.

The predictive significance of chromobox family members in prostate cancer in humans.

PURPOSE: The Chromobox (CBX) family proteins are crucial elements of the epigenetic regulatory machinery and play a significant role in the development and advancement of cancer. Nevertheless, there is limited understanding regarding the role of CBXs in development or progression of prostate cancer (PCa). Our objective is to develop a unique prognostic model associated with CBXs to improve the accuracy of predicting outcomes of patients with PCa. METHODS: Data from TCGA and GEO databases were analyzed to assess differential expression, prognostic value, gene pathway enrichment, and immune cell infiltration. COX regression analysis was utilized to identify the independent prognostic factors that impact disease-free survival (DFS). The expression of CBX2 and FOXP3+ cells infiltration was verified by immunohistochemical staining of clinical tissue sections. In vitro proliferation, migration and invasion assay were conducted to examine the function of CBX2. RNA-seq was employed to examine the CBX2 related pathway enrichment. RESULTS: CBX2, CBX3, CBX4, and CBX8 were upregulated, while CBX6 and CBX7 were downregulated in PCa tissues. CBXs expression varied by stage and grade. Elevated expression of CBX1, CBX2, CBX3, CBX4 and CBX8 is correlated with poor outcome. CBX2 expression, T stage, and Gleason score were independent prognostic factors. The expression level of CBX2 in PCa tissues was significantly higher than that in adjacent normal tissues. More Treg infiltration was observed in the group with high CBX2 expression. CBX2 expression affected PCa cell growth, migration, and invasion. CONCLUSIONS: CBX2 is involved in the development and advancement of PCa, suggesting its potential as a reliable prognostic indicator for PCa patients.

Integrated analysis reveals an aspartate metabolism-related gene signature for predicting the overall survival in patients with hepatocellular carcinoma.

BACKGROUND: Deregulating cellular metabolism is one of the prominent hallmarks of malignancy, with a critical role in tumor survival and growth. However, the role of reprogramming aspartate metabolism in hepatocellular carcinoma (HCC) are largely unknown. METHODS: The multi-omics data of HCC patients were downloaded from public databases. Univariate and multivariate stepwise Cox regression were used to establish an aspartate metabolism-related gene signature (AMGS) in HCC. The Kaplan-Meier and receiver operating characteristic curve analyses were performed to evaluate the predictive ability for overall survival (OS) in HCC patients. Gene set enrichment analysis and immune infiltration analysis were operated to determine the potential mechanisms underlying the AMGS. Single-cell RNA sequencing (scRNA-seq) data of liver cancer stem cells were visualized by t-SNE algorithm. In vivo and in vitro experiments were implemented to investigate the biological function of CAD in HCC. In addition, a nomogram based on the AMGS and clinicopathologic characteristics was constructed by univariate and multivariate Cox regression analyses. RESULTS: Patients in the high-AMGS subgroup exerted advanced tumor status and poor prognosis. Mechanistically, the high-AMGS subgroup patients had significantly enhanced proliferation and stemness-related pathways, increased infiltration of regulatory T cells and upregulated expression levels of suppressive immune checkpoints in the tumor immune microenvironment. Notably, scRNA-seq data revealed CAD, one of the aspartate metabolism-related gene, is significantly upregulated in liver cancer stem cells. Silencing CAD inhibited proliferative capacity and stemness properties of HCC cells in vitro and in vivo. Finally, a novel nomogram based on the AMGS showed an accurate prediction in HCC patients. CONCLUSIONS: The AMGS represents a promising prognostic value for HCC patients, providing a perspective for finding novel biomarkers and therapeutic targets for HCC.

Hepatitis B virus X protein represses expression of tumor suppressor PTPN18 in hepatocellular carcinoma.

HBV-associated hepatocellular carcinoma (HCC) represents the prevalent form of HCC, with HBx protein being a crucial oncoprotein. Numerous members of the protein tyrosine phosphatase non-receptor (PTPN) family have been confirmed to be significantly associated with the occurrence and progression of malignant tumors. Our group has previously identified the involvement of PTPN13 in HCC. However, the roles of other PTPNs in HCC still requires further investigation. In this study, we found PTPN18 expression was significantly downregulated within HCC tissues compared to that in adjacent non-tumor tissues and normal liver tissues. Functionally, PTPN18 exerted inhibitory effects on the proliferation, migration, invasion, and sphere-forming capability of HCC cells, while concurrently promoting apoptotic processes. Through phospho-protein microarray screening followed by subsequent validation experiments, we identified that PTPN18 could activate the p53 signaling pathway and suppress the AKT/FOXO1 signaling cascade in HCC cells. Moreover, we found that the HBx protein mediated the repression of PTPN18 expression by upregulating miR-128-3p. Collectively, our study unveiled the role of PTPN18 as a tumor suppressor in HBV-related HCC. Implications: Our findings revealed PTPN18 might serve as a potential diagnostic and therapeutic target for HBV-related HCC.

HMMR promotes prostate cancer proliferation and metastasis via AURKA/mTORC2/E2F1 positive feedback loop.

Although dysregulated HMMR is linked to prostate cancer (PCa) prognosis, the precise mechanisms remain unclear. Here, we sought to elucidate the role of HMMR in PCa progression as well as underlying mechanism. Herein, we found that upregulation of HMMR frequently observed in PCa samples and was associated with poor prognosis. Additionally, HMMR significantly promoted PCa proliferation and metastasis through gain- and loss-of function approaches in vitro and in vivo. Mechanistically, HMMR may interact with AURKA and elevated AURKA protein level through inhibiting ubiquitination-mediated degradation, which subsequently activated mTORC2/AKT pathway to ensure the reinforcement of PCa progression. Moreover, upregulated E2F1 caused from sustained activation of mTORC2/AKT pathway in turn function as transcription factor to promote HMMR transcription, thereby forming a positive feedback loop to trigger PCa progression. Importantly, administration of the mTOR inhibitor partially antagonised HMMR-mediated PCa progression in vivo. In summary, we not only reveal a novel possible post-translation mechanism mediated by HMMR involved in AURKA regulation, but also describe a positive feedback loop that contributes to PCa deterioration, suggesting HMMR may serve as a potential promising therapeutic target in PCa.

Application and Resistance Mechanisms of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma.

Lenvatinib, a multitargeted tyrosine kinase inhibitor (TKI), is one of the preferred targeted drugs for the treatment of advanced hepatocellular carcinoma (aHCC). Since the REFLECT study showed that lenvatinib was noninferior to sorafenib in overall survival (OS), lenvatinib monotherapy has been widely used for aHCC. Moreover, lenvatinib combination therapy, especially lenvatinib combined with immune checkpoint inhibitors (ICIs), has shown more encouraging clinical results. However, drug development and comprehensive treatment have not significantly improved the prognosis, and lenvatinib resistance is often encountered in treatment. The underlying molecular mechanism of lenvatinib resistance is still unclear, and studies to solve drug resistance are ongoing. The molecular mechanisms of lenvatinib resistance in patients with aHCC include the regulation of signaling pathways, the regulation of noncoding RNAs, the impact of the immune microenvironment, tumor stem cell activation and other mechanisms. This review aims to (1) summarize the progress of lenvatinib in treating aHCC, (2) delineate the known lenvatinib resistance mechanisms of current therapy, and (3) describe the development of therapeutic methods intended to overcome these resistance mechanisms.

Analysis of the potential association between ferroptosis and immune in hepatocellular carcinoma and their relationship with prognosis.

Background: The development of targeted therapy and immunotherapy has enriched the treatment of hepatocellular carcinoma (HCC), however, have had poor or no reponse, or even no response. Previous research suggested that ferroptosis and tumor immune microenvironment (TIME) may have a fundamental impact on efficacy during HCC immunotherapy and targeted therapy. Therefore, there is a clinical need to develop a signature that categorizes HCC patients in order to make more accurate clinical decisions. Methods: Clinical data and gene expression data of HCC patients were obtained from The Cancer Genome Atlas (TCGA) portal and International Cancer Genome Consortium (ICGC) portal. To identify ferroptosis-related immune-related genes (ferroptosis-related IRGs), Pearson correlation analysis was conducted. The ferroptosis-related IRGs prognostic signature (FIPS) was constructed using Univariate Cox and LASSO Cox algorithms. The predictive effectiveness of FIPS was evaluated using Receiver Operating Characteristic (ROC) curves and survivorship curve. The correlation ship between FIPS and TIME was evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT. The relationship between FIPS and immunotherapy responsiveness was evaluated using immunophenoscore. The expression level of 10 ferroptosis-related IRGs in normal liver tissues and HCC tissues was compared using immunohistochemistry. Finally, we established a nomogram (based on FIPS, TNM stage, and age) for clinical application. Results: The FIPS was established with ten ferroptosis-related IRGs. The high-FIPS subgroup showed a poor clinical prognosis and an obviously higher proportion of HCC patients with advanced TNM stage, high WHO grade and high alpha fetoprotein(AFP) value. Analysis of TIME indicated that patients in the high-FIPS subgroup may be in immunosuppressed state. Meanwhile, we found that ferroptosis may be inhibited in the high-FIPS subgroup and this subgroup may be impervious to immunotherapy and sorafenib. Conclusion: We constructed a novel potential prognostic signature for HCC patients that predicts overall survival, ferroptosis and immune status, sorafenib sensitivity, and immunotherapy responsiveness.

Prognostic nomogram for predicting cancer-specific survival in patients with resected hilar cholangiocarcinoma: a large cohort study.

Background: The aim of the study was to establish and validate a novel prognostic nomogram of cancer-specific survival (CSS) in resected hilar cholangiocarcinoma (HCCA) patients. Methods: A training cohort of 536 patients and an internal validation cohort of 270 patients were included in this study. The demographic and clinicopathological variables were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate Cox regression analysis were performed in the training cohort, followed by the construction of nomogram for CSS. The performance of the nomogram was assessed by concordance index (C-index) and calibration plots and compared with the American Joint Committee on Cancer (AJCC) staging systems. Decision curve analysis (DCA) was applied to measure the predictive power and clinical value of the nomogram. Results: The nomogram incorporating age, tumor size, tumor grade, lymph node ratio (LNR) and T stage parameters was with a C-index of 0.655 in the training cohort, 0.626 in the validation cohort, compared with corresponding 0.631, 0.626 for the AJCC 8th staging system. The calibration curves exhibited excellent agreement between CSS probabilities predicted by nomogram and actual observation in the training cohort and validation cohort. DCA indicated that this nomogram generated substantial clinical value. Conclusions: The proposed nomogram provided a more accurate prognostic prediction of CSS for individual patients with resected HCCA than the AJCC 8th staging system, which might be served as an effective tool to stratify resected HCCA patients with high risk and facilitate optimizing therapeutic benefit.

A Novel Risk Factor Model Based on Glycolysis-Associated Genes for Predicting the Prognosis of Patients With Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) is one of the most prevalent cancers among males, and its mortality rate is increasing due to biochemical recurrence (BCR). Glycolysis has been proven to play an important regulatory role in tumorigenesis. Although several key regulators or predictors involved in PCa progression have been found, the relationship between glycolysis and PCa is unclear; we aimed to develop a novel glycolysis-associated multifactor prediction model for better predicting the prognosis of PCa. METHODS: Differential mRNA expression profiles derived from the Cancer Genome Atlas (TCGA) PCa cohort were generated through the "edgeR" package. Glycolysis-related genes were obtained from the GSEA database. Univariate Cox and LASSO regression analyses were used to identify genes significantly associated with disease-free survival. ROC curves were applied to evaluate the predictive value of the model. An external dataset derived from Gene Expression Omnibus (GEO) was used to verify the predictive ability. Glucose consumption and lactic production assays were used to assess changes in metabolic capacity, and Transwell assays were used to assess the invasion and migration of PC3 cells. RESULTS: Five glycolysis-related genes were applied to construct a risk score prediction model. Patients with PCa derived from TCGA and GEO (GSE70770) were divided into high-risk and low-risk groups according to the median. In the TCGA cohort, the high-risk group had a poorer prognosis than the low-risk group, and the results were further verified in the GSE70770 cohort. In vitro experiments demonstrated that knocking down HMMR, KIF20A, PGM2L1, and ANKZF1 separately led to less glucose consumption, less lactic production, and inhibition of cell migration and invasion, and the results were the opposite with GPR87 knockdown. CONCLUSION: The risk score based on five glycolysis-related genes may serve as an accurate prognostic marker for PCa patients with BCR.

Clinicopathological significance and prognostic value of cancer-associated fibroblasts in prostate cancer patients.

INTRODUCTION: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment were considered to play an essential role in tumor growth and development. However, few studies have assessed the prognostic and clinicopathological significance of CAFs in prostate cancer (PCa) patients. METHODS: One hundred thirty pairs of PCa tissues and normal adjacent tissues (NATs) were immunostained with fibroblast activation protein and α-smooth muscle actin to quantify CAFs. Bioinformatics analysis was used to uncover the possible biological functions of CAFs. RESULTS: More CAFs were identified in PCa tissues than in NATs. High density of CAFs may be associated with advanced-stage disease, higher Gleason scores, lymphatic metastases, higher PSA, and poor biochemical recurrence-free survival in PCa. Bioinformatics analysis showed that CAFs may regulate tumor progression and recurrence through ECM modification, PI3K-Akt signaling pathway and regulation of cytoskeleton. CONCLUSION: In summary, our study uncovered the clinicopathological significance and potential mechanism of CAFs and indicated that CAFs may be a useful prognostic biomarker in PCa.

Molecular Targets of Ferroptosis in Hepatocellular Carcinoma.

Ferroptosis is a special form of regulatory cell death caused by the accumulation of intracellular iron and lipid peroxidation. Here, we summarize the research progress on ferroptosis in hepatocellular carcinoma (HCC), trace the development of the concept of ferroptosis and its key regulatory factors, and discuss the application value of ferroptosis in the treatment of HCC from different perspectives. We believe that exploring the relationship between ferroptosis and HCC and clarifying the metabolism and expression of ferroptosis-specific genes and molecules will accelerate the development of novel ferroptosis-related molecules as HCC markers and therapeutic targets. We hope to provide a theoretical basis for better diagnosis and treatment to effectively improve the prognosis of patients with HCC.