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Background: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC., Methods: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP)., Results: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001)., Conclusions: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Aim: To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice., Methods: Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice. After acteoside administration in DBA/2J mice, anterior segment observation, intraocular pressure (IOP) monitoring, electrophysiology examination, and hematoxylin and eosin staining were used to analyze any potential effects. Immunohistochemistry (IHC) assays were used to verify the proteomics results. Furthermore, retinal ganglion cell 5 (RGC5) cell proliferation was assessed with cell counting kit-8 (CCK-8) assays. Serta domain-containing protein 4 (Sertad4) mRNA and protein expression levels were measured by qRT-PCR and Western blot analysis, respectively., Results: Proteomics analysis suggested that Sertad4 was the most significantly differentially expressed protein. Compared with the saline group, the acteoside treatment group showed decreased IOP, improved N1-P1 wave amplitudes, thicker retina, and larger numbers of cells in the ganglion cell layer (GCL). The IHC results showed that Sertad4 expression levels in DBA/2J mice treated with acteoside were significantly lower than in the saline group. Acteoside treatment could improve RGC5 cell survival and reduce the Sertad4 mRNA and protein expression levels after glutamate injury., Conclusion: Sertad4 is differentially expressed in DBA/2J mice. Acteoside can protect RGCs from damage, possibly through the downregulation of Sertad4, and has a potential use in glaucoma treatment., Competing Interests: Conflicts of Interest: Hao HJ, None; Li YH, None; Yu B, None; Liu X, None; Zhang Y, None; Xing XL, None., (International Journal of Ophthalmology Press.)

Background: Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. FORKHEAD BOX I3 (FOXI3) is a susceptibility gene for HFM, and mice with loss of function of Foxi3 did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by FOXI3 deficiency remains unclear till now., Method: In this study, we first constructed a Foxi3 deficiency (Foxi3 -/- ) mouse model to verify the craniofacial phenotype of Foxi3 -/- mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real-time PCR., Results: By observing the phenotype of Foxi3 -/- mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by Foxi3 deficiency may be involved in the PI3K-Akt signaling pathway. Quantitative real-time PCR results showed that the expression of PI3K-Akt signaling pathway-related gene Akt2 was significantly increased in Foxi3 -/- mice., Conclusion: The craniofacial dysmorphism caused by the deficiency of Foxi3 may be related to the expression of Akt2 and PI3K-Akt signaling pathway. This study laid a foundation for understanding the function of FOXI3 and the pathogenesis and treatment of related craniofacial dysmorphism caused by FOXI3 dysfunction., (© 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Studies have shown that a series of molecular events caused by oxidative stress is associated with ferroptosis and oxidation after ischemic stroke (IS). Differential analysis was performed to identify differentially expressed mRNA (DEmRNAs) between IS and control groups. Critical module genes were identified using weighted gene co-expression network analysis (WGCNA). DEmRNAs, critical module genes, oxidative stress-related genes (ORGs), and ferroptosis-related genes (FRGs) were crossed to screen for intersection mRNAs. Candidate mRNAs were screened based on the protein-protein interaction (PPI) network and the MCODE plug-in. Biomarkers were identified based on two types of machine learning algorithms, and the intersection was obtained. Functional items and related pathways of the biomarkers were identified using gene set enrichment analysis (GSEA). Finally, single-sample GSEA (ssGSEA) and Wilcoxon tests were used to identify differential immune cells. An miRNA-mRNA-TF network was created. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression levels of biomarkers in the IS and control groups. There were 8287 DE mRNAs between the IS and control groups. The genes in the turquoise module were selected as critical module genes for IS. Thirty intersecting mRNAs were screened for overlaps. Seventeen candidate mRNAs were also identified. Four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) were identified using two types of machine-learning algorithms. GSEA results indicated that the biomarkers were associated with steroid biosynthesis. Nine types of immune cells (activated B cells and neutrophils) were markedly different between the IS and control groups. We identified 3747 miRNA-mRNA-TF regulatory pairs in the miRNA-mRNA-TF regulatory network, including hsa-miR-4469-CDKN1A-BACH2 and hsa-miR-188-3p-GPX4-ATF2. CDKN1A, PRDX1, and PRDX6 were upregulated in IS samples compared with control samples. This study suggests that four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) are significantly associated with IS. This study provides a new reference for the diagnosis and treatment of IS., (© 2024. The Author(s).)

Background: The existing literature indicates that repetitive transcranial magnetic stimulation (rTMS) can potentially enhance the prognosis of poststroke aphasia (PSA). Nevertheless, these investigations did not identify the most effective parameters or settings for achieving optimal treatment outcomes. This study involved a meta-analysis aimed to identify the optimal variables for rTMS in treating post-infarction aphasia to guide the use of rTMS in rehabilitating PSA., Methods: PubMed, Embase, and Cochrane Library databases were searched from inception to May 2023, and articles were reviewed manually using subject words and free words and supplemented with references from the included literature to obtain additional relevant literature. The search terms included "poststroke aphasia" and "repetitive transcranial magnetic stimulation (rTMS)" repetitive transcranial magnetic stimulation. Additionally, a review of the reference lists of previously published systematic reviews identified through the Cochrane Database of Systematic Reviews (search terms: poststroke aphasia, rTMS; restrictions: none) and PubMed (search terms: poststroke aphasia, rTMSs; restrictions: systematic review or meta-analysis) was performed. Information from studies involving different doses of rTMS in PSA was independently screened and extracted by 2 researchers., Results: This meta-analysis included 387 participants with PSA across 18 randomized controlled trials. The results showed that the total pulse had a trend toward a significant correlation with the treatment effect (P = 0.088), while all other variables did not correlate significantly. When rTMS was not grouped by stimulus parameter and location, our nonlinear results showed that when the total pulses were 40,000 (standardized mean difference (SMD):1.86, 95% credible interval (CrI) 0.50 to 3.33), the pulse/session was 1000 (SMD:1.05, 95% CrI 0.55-1.57), and an RMT of 80% (SMD:1.08, 95% CrI 0.60-1.57) had the best treatment effect. When rTMS was grouped by stimulus parameters and location, our nonlinear results showed that when the total low-frequency (LF)-rTMS-right inferior frontal gyrus (RIFG) pulse was 40,000 (SMD:1.76, 95% CrI:0.36-3.29), the pulse/session was 1000 (SMD:1.06, 95% CrI:0.54-1.59). Optimal results were obtained with an RMT of 80% (SMD:1.14, 95% CrI 0.54 - 1.76)., Conclusions: The optimal treatment effects of rTMS for PSA may be obtained with a total pulse of 40,000, a pulse/session of 1000, and an RMT of 80%. Further rigorous randomized controlled studies are required to substantiate the validity of these results., (© 2023. The Author(s).)

Cuproptosis is a novel type of copper-induced cell death and is considered as a new therapeutic target for many cancers. Distant metastases occur in about 40% of patients with advanced renal cell carcinoma (RCC), with a poor 5-year prognosis of about 10%. Through a series of comprehensive analyses, four differentially expressed cuproptosis-related lncRNAs (DECRLs) were identified as candidate biomarkers for RCC. The risk model constructed by using these four DECRLs can better predict the prognosis of patients with RCC, which is determined by the receiver operating characteristic (Time dependent area under curve value at 1-year, 3-year, 5-year, and 10-year were 0.82, 0.80, 0.76, and 0.73 respectively). There were significant differences in immune status between high-risk and low-risk RCC patients. The differentially expressed gene enrichment terms between high- and low-risk patients was also dominated by immune-related terms. The risk score was also correlated with immunotherapy as measured by the tumor immune dysfunction and exclusion (TIDE) score. In addition, we also found that the sensitivity of many chemotherapy drugs varies widely between high- and low-risk patients. The sensitivity of the three chemotherapy drugs (AZD4547, Vincristine, and WEHI-539) varied among high- and low-risk patients, and was significantly negatively correlated with risk values, suggesting that they could be used as clinical treatment drugs for RCC. Our study not only obtained four potential biomarkers, but also provided guidance for immunotherapy and chemotherapy treatment of RCC, as well as new research strategies for the screening of other cancer biomarkers and sensitive drugs.

Breast cancer (BC) is one of the most common malignancies affecting women. Ferroptosis is a novel cancer treatment option. The present study is aimed to identify suitable ferroptosis-related lncRNAs to predict and diagnose BC. Differential expression and Cox regression analyses were used to screen suitable prognostic biomarkers and construct a suitable risk model. We identified four ferroptosis-related differentially expressed lncRNAs (FR-DELs) (LINC01152, AC004585.1, MAPT-IT1, and AC026401.3), which were independently correlated with the overall survival of BC patients. The area under the curve value of the prognostic model using those four biomarkers was over 0.60 in all three groups. The sensitivity and specificity of the diagnostic model using those four biomarkers were 86.89% and 86.73%, respectively. Our present study indicated that these four FR-DELs (LINC01152, AC004585.1, MAPT-IT1, and AC026401.3) could be prognostic biomarkers for BC, although clinical validation studies are required., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Zhi-Yong Yao et al.)

Background: Ferroptosis and immunity are novel treatments that target several cancers, including kidney renal clear cell carcinoma (KIRC). Long noncoding RNAs (lncRNAs) are an important class of gene expression regulators that play fundamental roles in the regulation of ferroptosis and immunity. We aimed to identify ferroptosis- and immune-related lncRNAs as biomarkers in patients with KIRC. Methods: Corresponding data for each patient with KIRC were obtained from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were used to identify candidate biomarkers followed by least absolute shrinkage and selection operator (LASSO) regression analyses, weighted gene coexpression network analysis (WGCANA), and gene set enrichment analysis (GSEA). Results: Three ferroptosis- and immune-related differentially expressed lncRNAs (FI-DELs) (AC124854.1, LINC02609, and ZNF503-AS2) were markedly and independently correlated with the overall survival (OS) of patients with KIRC. The area under the curve (AUC) value of the prognostic model in the entire group using the three FI-DELs was > 0.70. The sensitivity and specificity of the diagnostic model using the three FI-DELs were 0.8586 and 0.9583, respectively. Conclusion: The present study found that AC124854.1, LINC02609, and ZNF503-AS2 were considerably and independently correlated with the OS of patients with KIRC, suggesting that the three FI-DELs could be used as prognostic and diagnostic biomarkers for patients with KIRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Han, Wang, Liu and Xing.)

Background: Kidney cancer (KC) is one of the most challenging cancers due to its delayed diagnosis and high metastasis rate. The 5-year survival rate of KC patients is less than 11.2%. Therefore, identifying suitable biomarkers to accurately predict KC outcomes is important and urgent., Methods: Corresponding data for KC patients were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. Systems biology/bioinformatics/computational approaches were used to identify suitable biomarkers for predicting the outcome and immune landscapes of KC patients., Results: We found two ferroptosis- and immune-related differentially expressed genes (FI-DEGs) ( Klotho ( KL ) and Sortilin 1 ( SORT1 )) independently correlated with the overall survival of KC patients. The area under the curve (AUC) values of the prognosis model using these two FI-DEGs exceeded 0.60 in the training, validation, and entire groups. The AUC value of the 1-year receiver operating characteristic (ROC) curve reached 0.70 in all the groups., Conclusions: Our present study indicated that KL and SORT1 could be prognostic biomarkers for KC patients. Whether this model can be used in clinical settings requires further validation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Han, Wang, Long, Qiu and Xing.)

Background: Almost 40% of patients with kidney renal clear cell carcinoma (KIRC) with advanced cancers eventually develop to metastases, and their 5-year survival rates are approximately 10%. Aberrant DNA methylations are significantly associated with the development of KIRC. The aim of our present study was to identify suitable ferroptosis- and immune-related (FI) biomarkers correlated with aberrant methylations to improve the prognosis and diagnosis of KIRC., Methods: ChAMP and DESeq2 in R (3.6.2) were used to screen the differentially expressed methylation probes and differentially expressed genes, respectively. Univariate and multivariate Cox regression were used to identify the overall survival (OS)-related biomarkers., Results: We finally identified five FI biomarkers ( CCR4 , CMTM3 , IFITM1 , MX2 , and NR3C2 ) that were independently correlated with the OS of KIRC. The area under the curve value of the receiver operating characteristic value of prognosis model was 0.74, 0.68, and 0.72 in the training, validation, and entire cohorts, respectively. The sensitivity and specificity of the diagnosis model were 0.8698 and 0.9722, respectively. In addition, the prognosis model was also significantly correlated with several immune cells and factors., Conclusion: Our present study suggested that these five FI-DEGs ( CCR4 , CMTM3 , IFITM1 , MX2 , and NR3C2 ) could be used as prognosis and diagnosis biomarkers for patients with KIRC, but further cross-validation clinical studies are still needed to confirm them., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xing, Liu, Liu, Zhou, Zhang, Zuo, Bu, Duan, Zhou and Xiao.)

LncRNAs and miRNAs are correlated with the pathogenesis of myocardial ischemia-reperfusion injury (MIRI). Whether lncRNA ROR or miR-185-5p plays a crucial role in MIRI is still unclear. In in-vitro, human cardiac myocytes (HCMs) were treated with hypoxia/reoxygenation (H/R). Wistar rats were used to set up an in-vitro I/R model by means of recanalization after ligation. Evaluation of the myocardial injury marker lactate dehydrogenase (LDH) in HCMs cells was performed. The expression of miR-185-5p and ROR, IL-1β, and IL-18 were detected by qRT-PCR. ELISA was also performed to evaluate the secretion of IL-1β and IL-18. Western blotting was carried out to determine CDK6, NLRP3, GSDMD-N, ASC, and cleaved-caspase1 protein expression. The relationship between miR-185-5p and CDK6 or ROR was confirmed by a dual-luciferase reporter assay. Our findings revealed that H/R treated HCMs showed a significantly decreased miR-185-5p expression and increased expression of CDK6 and ROR. ROR knockdown reduced H/R induced pyroptosis and inflammation, while knockdown of miR-185-5p accelerated the effect. Furthermore, miR-185-5p was negatively regulated and absorbed by ROR in HCMs. Overexpression of miR-185-5p reversed the H/R-induced cell pyroptosis and upregulation of LDH, IL-1β, and IL-18. In HCMs, miR-185-5p was also negatively regulated and related to CDK6 expression. Moreover, overexpression of CDK6 significantly inhibited the effects of miR-185-5p mimics on the inflammatory response and pyroptosis of HCMs. Knockdown of ROR alleviated H/R-induced myocardial injury by elevating miR-185-5p and inhibiting CDK6 expression. Taken together, our results show that the ROR/miR-185-5p/CDK6 axis modulates cell pyroptosis induced by H/R and the inflammatory response of HCMs., (© 2022. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

Background: Heterogeneity of breast cancer (BRCA) is significantly correlated with its prognosis. Target therapy for ferroptosis and immunity is a new cancer treatment option discovered in recent years. In the present study, we aimed to identify ferroptosis- and immune-related long non-coding RNAs (lncRNAs) to accurately predict the prognosis and diagnosis of patients with breast infiltrating duct and lobular carcinoma by integrated analyses., Methods: The corresponding data for the patients with breast infiltrating duct and lobular carcinoma by integrated analyses were obtained from The Cancer Genome Atlas (TCGA). Analyses of univariate and multivariate Cox regressions were used to identify the suitable candidate biomarkers., Results: We found that seven ferroptosis- and immune-related differentially expressed lncRNAs (FI-DELs) (AC007686.3, AC078883.1, ADAMTS9-AS1, AL035661.1, CBR3-AS1, FTX, and TMEM105) were correlated with the overall survival of patients with breast infiltrating duct and lobular carcinoma. The areas under the receiver operating characteristic (AUCs) value of the prognosis model were all over 0.6 in training, validation, and entire groups. The sensitivity and specificity of the diagnosis model was 87.84% and 97.06%, respectively., Conclusions: Through a series of bioinformatics analyses, we found that the seven FI-DELs could serve as prognostic and diagnostic biomarkers for patients with breast infiltrating duct and lobular carcinoma. However, whether these seven biomarkers could be really applied to the clinic requires further investigations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wei, Zhu, Jiang and Xing.)

Background: Ferroptosis is a novel regulated cell death that is characterized by iron-dependent oxidative damage. Renal cancer is the second most common cancer of the urinary system, which is highly correlated with iron metabolism. The aim of our present study was to identify suitable ferroptosis-related prognosis signatures for renal cancer. Methods: We downloaded the RNA-seq count data of renal cancer from The Cancer Genome Atlas database and used the DESeq2, Survival, and Cox regression analyses to screen the prognosis signatures. Results: We identified 5 ferroptosis-related differentially expressed lncRNAs (FR-DELs) (DOCK8-AS1, SNHG17, RUSC1-AS1, LINC02609, and LUCAT1) to be independently correlated with the overall survival (OS) of patients with renal cancer. The risk assessment model and diagnosis model constructed by those 5 FR-DELs could well predict the outcome and the diagnosis of renal cancer. Conclusion: Our present study not only suggested those 5 FR-DELs could be used as prognosis and diagnosis signatures for renal cancer but also provided strategies for other cancers in the screening of ferroptosis-related biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shu, Zhang, Yao and Xing.)

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are among the most common malignancies of the female genital tract. Ferroptosis and immunity regulate each other and play important roles in the progression of CESC. The present study aimed to screen ferroptosis- and immune-related differentially expressed genes (FI-DEGs) to identify suitable prognostic signatures for patients with CESC. We downloaded the RNAseq count data and corresponding clinical information of CESC patients from The Cancer Genome Atlas database; obtained recognized ferroptosis- and immune-related genes from the FerrDb and ImmPort databases, respectively; and screened for suitable prognostic signatures using a series of bioinformatics analyses. We identified eight FI-DEGs ( CALCRL , CHIT1 , DES , DUOX1 , FLT1 , HELLS , SCD , and SDC1 ) that were independently correlated with the overall survival of patients with CESC. The prediction model constructed using these eight FI-DEGs was also independently correlated with overall survival. Both the sensitivity and specificity of the prediction model constructed using these eight signatures were over 60%. The comprehensive index of ferroptosis and immune status was significantly correlated with the immunity of patients with CESC. In conclusion, the risk assessment model constructed with these eight FI-DEGs predicted the CESC outcomes. Therefore, these eight FI-DEGs could serve as prognostic signatures for CESC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xing, Yin, Yao and Xing.)

Almost 75% of renal cancers are renal clear cell carcinomas (KIRC). Accumulative evidence indicates that epigenetic dysregulations are closely related to the development of KIRC. Cancer immunotherapy is an effective treatment for cancers. The aim of this study was to identify immune-related differentially expressed genes (IR-DEGs) associated with aberrant methylations and construct a risk assessment model using these IR-DEGs to predict the prognosis of KIRC. Two IR-DEGs (SLC11A1 and TNFSF14) were identified by differential expression, correlation analysis, and Cox regression analysis, and risk assessment models were established. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.6907. In addition, we found that risk scores were significantly associated with 31 immune cells and factors. Our present study not only shows that two IR-DEGs can be used as prognosis signatures for KIRC, but also provides a strategy for the screening of suitable prognosis signatures associated with aberrant methylation in other cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yao, Xing, Liu and Xing.)

Background: Ferroptosis is a recently recognised new type of cell death which may be a potential target for cancer therapy. In the present study, we aimed to screen ferroptosis-related differentially expressed long non-coding RNAs as biomarkers to predict the outcome of kidney renal clear cell carcinoma., Methods: RNAseq count data and corresponding clinical information were obtained from the Cancer Genome Atlas database. Lists of ferroptosis-related genes and long non-coding RNAs were obtained from the FerrDb and GENCODE databases, respectively. The candidate prognostic signatures were screened by Cox regression analyses and least absolute shrinkage and selection operator analyses., Results: Three ferroptosis-related long non-coding RNAs (DUXAP8, LINC02609, and LUCAT1) were significantly correlated with the overall survival of kidney renal clear cell carcinoma independently. Kidney renal clear cell carcinoma patients with high-risk values displayed worse OS. Meanwhile, the expression of these three ferroptosis-related long non-coding RNAs and their risk scores were significantly correlated with clinicopathological features. Principal component analyses showed that patients with kidney renal clear cell carcinoma have differential risk values were well distinguished by the three ferroptosis-related long non-coding RNAs., Conclusions: The present study suggests that the risk assessment model constructed by these three ferroptosis-related long non-coding RNAs could accurately predict the outcome of kidney renal clear cell carcinoma. We also provide a novel perspective for cancer prognosis screening., (© 2021. The Author(s).)

Colorectal cancer (CRC) is one of the most common cancers. Almost 1/3 of CRC are rectal cancer, and 95% of rectal cancers are rectal adenocarcinoma (READ). Increasing evidences indicated that long noncoding RNAs (lncRNAs) have important role in the genesis and development of cancers. The purpose of our present study was to identify the differential expression lncRNAs which potentially related with immune cells infiltration and establish a risk assessment model to predict the clinical outcome for READ patients. We obtained three immune-related differential expression lncRNAs (IR-DELs) (C17orf77, GATA2-AS1, and TPT1-AS1) by differential expression analysis following correlation analysis and Cox regression analysis. A risk assessment model were constructed by integrating these analysis results. We then plotted the 1-, 3-, and 5-year ROC curves depending on our risk assessment model, which suggested that all AUC values were over 0.7. In addition, we found that the risk assessment model was correlated with several immune cells and factors. This study suggested that those three signatures (C17orf77, GATA2-AS1, and TPT1-AS1) screened by pairing IR-DELs could be prognosis markers for READ patients and might benefit them from antitumor immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xing, Xing, Huang, Yao and Liu.)

Colorectal cancer (CRC) is one of the most common cancers. Almost 80% of CRC cases are colon adenocarcinomas (COADs). Several studies have indicated the role of immunotherapy in the treatment of various cancers. Our study aimed to identify immune-related long non-coding RNAs (lncRNAs) and to use them to construct a risk assessment model for evaluating COAD prognosis. Using differential expression, correlation, and Cox regression analyses, we identified three immune-related differentially expressed lncRNAs (IR-DELs) and used them to construct a risk assessment model. The area under the curve (AUC) for each receiver operating characteristic (ROC) curve at 3-, 5-, and 10-years were greater than 0.6. In addition, the risk assessment model was correlated with several immune cells and factors. The three IR-DELs (AC124067.4, LINC02604, and MIR4435-2HG) identified in this study can be used to predict outcomes for patients with COAD and might help in identifying those who can benefit from anti-tumor immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xing, Zhang, Yao, Xing, Wang, Liu and Huang.)

Background: To know the expression of Mesenchymal-Epithelial Transition factor (MET) and Fatty Acid Synthase (FASN) in Triple Negative Breast Cancer (TNBC) patients, as well as its relationship with clinical pathological characteristic and prognosis., Methods: we used immunohistochemistry staining to detect the expression of MET and FASN for those 218 TNBC patients, and analyze their relationship with the clinical pathological characteristic and prognosis., Results: 130 and 65 out of 218 TNBC patients were positive for MET in the cancer and adjacent tissues respectively. 142 and 30 out of 218 TNBC patients were positive for FASN in the cancer and adjacent tissues respectively. Positive expression of MET and FASN were significantly correlated with lymph node metastasis, pathological TNM, and pathological Stage. In addition, the positive expression of MET and FASN were correlated with recurrence and metastasis. The combined use of MET and FASN can better predict the survival condition., Conclusions: Our results indicated that MET and FASN showed good predictive ability for TNBC. Combined use of MET and FASN were recommended in order to make a more accurate prognosis for TNBC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jiang, Xing, Zhang, Yi, Xu, Ou and Zhu.)

Background: Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC., Methods: In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model., Results: Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers., Conclusion: This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.

Background: Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cell carcinoma which has the worst overall survival rate. Almost 30% of patients with localized cancers eventually develop to metastases despite of early surgical treatment carried out. MicroRNAs (miRNAs) play a critical role in human cancer initiation, progression, and prognosis. The aim of our study was to identify potential prognosis biomarkers to predict overall survival of KIRC., Methods: All data were downloaded from an open access database The Cancer Genome Atlas. DESeq2 package in R was used to screening the differential expression miRNAs (DEMs) and genes (DEGs). RegParallel and Survival packages in R was used to analysis their relationships with the KIRC patients. David version 6.8 and STRING version 11 were used to take the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis., Results: We found 2 DEGs (TIMP3 and HMGCS1) and 3 DEMs (hsa-miR-21-5p, hsa-miR-223-3p, and hsa-miR-365a-3p) could be prognosis biomarkers for the prediction of KIRC patients. The constructed prognostic model based on those 2 DEGs could effectively predict the survival status of KIRC. And the constructed prognostic model based on those 3 DEMs could effectively predict the survival status of KIRC in 3-year and 5-year., Conclusion: The current study provided novel insights into the miRNA related mRNA network in KIRC and those 2 DEGs biomarkers and 3 DEMs biomarkers may be independent prognostic signatures in predicting the survival of KIRC patients.

Background: Colorectal cancer (CRC) is the third most common cancer in the world, and most of them are adenocarcinomas. CRC could be classified as colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) according to the original tumorigenesis position. Increasing evidences indicated that microRNAs (miRNAs) play an important role in the occurrence of multiple tumors., Methods: In this study, we firstly downloaded miRNA (COAD, 8 controls vs. 455 tumors; READ, 3 controls vs. 161 tumors) and mRNA (COAD, 41 controls vs. 478 tumors; READ, 10 controls vs. 166 tumors) data from The Cancer Genome Atlas (TCGA) database and then used DESeq2, RegParallel, miRDB, TargetScanHuman 7.2, DAVID 6.8, STRING, and Cytoscape software to identify the potential prognosis biomarkers., Results: We identified 175 differential expression miRNAs (DEMs) and 3747 differential expression genes (DEGs) in COAD and 184 DEMs and 3928 DEGs in READ. And then, we obtained 21 (13 in COAD and 8 in READ) DEMs associated with the survival rates, which correlated with 440 (217 in COAD and 223 in READ) overlapping DEGs. Through survival analysis for those overlapping DEGs, we found 11 (8 in COAD and 3 in READ) overlapping DGEs associated with survival rates of patients, which were correlated with 9 (7 in COAD and 2 in READ) DEMs significantly., Conclusion: In this study, we found several candidate prognostic biomarkers which have been identified in various cancers and also found several new prognosis biomarkers of COAD and READ. In conclusion, this analysis based on theoretical knowledge and clinical outcomes we have done needs further confirmation by more researches., Competing Interests: The authors declare no competing interests., (Copyright © 2020 Xiao-Liang Xing et al.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) contribute to tumorigenesis, progression and recurrence of various malignancies including Gallbladder carcinoma (GBC). Lnc-DILC is reported to be the tumor suppressor gene to play an important role in liver cancer stem cells (CSCs). However, the role of lnc-DILC in GBC remains to be elucidated. Herein, we show that lnc-DILC is upregulated in gallbladder CSCs and GBC patients' tissues. Knockdown of lnc-DILC attenuates the self-renewal, tumorigenicity, proliferation and metastasis of gallbladder CSCs. Mechanistically, lnc-DILC promotes gallbladder CSCs expansion via Wnt/β-catenin pathway. Special Wnt/β-catenin inhibitor FH535 diminishes the discrepancy of self-renewal, growth and metastasis between lnc-DILC interference GBC cells and their control cells. In conclusion, lnc-DILC drives gallbladder CSCs self-renewal, tumorigenicity, proliferation and metastasis by activating Wnt/β-catenin signaling, and may therefore prove to be a potential therapeutic target for GBC patients., (Copyright © 2019. Published by Elsevier B.V.)

Colorectal cancer (CRC) is one of the most common malignant tumors and one of the leading causes of cancer-related death in both men and women. The prognosis of CRC remains poor due to the advanced stage and cancer metastasis at the time of diagnosis. However, the exact mechanism of tumorigenesis in CRC remains unclear. Long non-coding RNAs (lncRNAs), which refer to transcripts longer than 200 nucleotides that are not translated into protein, are known to play important roles in multiple human cancers. Lnc-DILC is reported to be an important tumor suppressor gene and its inactivation is closely associated with liver cancer stem cells. However, the role of lnc-DILC in CRC remains to be elucidated. In the present study, we observed that lnc-DILC overexpression inhibited the growth and metastasis of CRC cells. Consistently, lnc-DILC knockdown facilitated the proliferation and metastasis of CRC cells. Mechanically, lnc-DILC suppressed CRC cell progression via IL-6/STAT3 signaling inactivation. More importantly, the specific STAT3 inhibitor S3I-201 and IL-6R inhibitor tocilizumab abolished the discrepancy of growth and metastasis capacity between lnc-DILC-interference CRC cells and control cells, which further confirmed that IL-6/STAT3 signaling was required in lnc-DILC-disrupted CRC cell growth and metastasis. Taken together, our results suggest that lnc-DILC is a novel CRC suppressor and may prove to be an inhibitor of CRC progression by inactivating IL-6/STAT3 signaling., (Copyright © 2018. Published by Elsevier B.V.)

Human health is significantly threatened by gastric cancer, which is the most common malignant tumor; although drastic, surgery is currently the only way to cure it. However, high recurrence rates and low survival rates are associated with the disease. Therefore, to improve the effectiveness of gastric cancer treatment and to increase the clinical cure rate, we investigated the effect of cyclosporin A particles of varying diameter on gastric cancer cell apoptosis. Flow cytometry was used to detect apoptosis induced by Annexin V-fluorescein isothiocyanate/propidium iodide-double labeling. We also determined the content of reactive oxygen species and the expression level of P-glycoprotein in cells after treatment with cyclosporin A. The results indicated that increases in the concentration and action time of cyclosporin A were associated with statistically significant increases in the apoptosis rate of gastric cancer cells when the experimental and control groups were compared (P < 0.05 and P < 0.01, respectively). In conclusion, during a certain action time and concentration range, cyclosporin A inhibits the proliferation of human gastric cancer cells and can induce their apoptosis.

Let-7 family microRNAs have been reported to be downregulated in human hepatocellular carcinoma in comparison with normal hepatic tissues. Among them, let-7g was identified as the lowest expression using real-time RT-PCR. However, the mechanism by which let-7g works in hepatocellular carcinoma remains unknown. Here, in our present study, we have had let-7g reexpressed in vitro in hepatocellular carcinoma cell lines MHCC97-H and HCCLM3 via transfection. The proliferation after reexpression of let-7g was assayed using MTT method; the migration and invasion after restoration were detected by wound-healing and Transwell assay, respectively. We found using Western-blotting that let-7g can regulate epithelial-mesenchymal transition (EMT) by downregulating K-Ras and HMGA2A after reexpresssion. Xenografted nude mice were used to observe whether or not reexpression of let-7g could have potential therapeutic ability. In vivo, to observe the association with let-7g expression and overall prognosis, 40 paired cases of hepatocellular carcinoma were analyzed using in situ hybridization (ISH). It was found that reexpression of let-7g can inhibit the proliferation, migration, and invasion significantly, and that low expression of let-7g was significantly associated with poorer overall survival. Taken together, let-7g could be used as a promising therapeutic agent in vivo in the treatment of hepatocellular carcinoma at the earlier stage.

Growing evidence from rodent models of temporal lobe epilepsy (TLE) indicates that dysregulation of the mammalian target of rapamycin (mTOR) pathway is involved in seizures and epileptogenesis. However, the role of the mTOR pathway in the epileptogenic process remains poorly understood. Here, we used an animal model of TLE and sclerotic hippocampus from patients with refractory TLE to determine whether cell-type specific activation of mTOR signaling occurs during each stage of epileptogenesis. In the TLE mouse model, we found that hyperactivation of the mTOR pathway is present in distinct hippocampal subfields at three different stages after kainate-induced seizures, and occurs in neurons of the granular and pyramidal cell layers, in reactive astrocytes, and in dispersed granule cells, respectively. In agreement with the findings in TLE mice, upregulated mTOR was observed in the sclerotic hippocampus of TLE patients. All sclerotic hippocampus (n = 13) exhibited widespread reactive astrocytes with overactivated mTOR, some of which invaded the dispersed granular layer. Moreover, two sclerotic hippocampus exhibited mTOR activation in some of the granule cells, which was accompanied by cell body hypertrophy. Taken together, our results indicate that mTOR activation is most prominent in reactive astrocytes in both an animal model of TLE and the sclerotic hippocampus from patients with drug resistant TLE.