Aldo-keto Reductase Family 1 Member B10 Research Articles

A Composite Blood Biomarker Including AKR1B10 and Cytokeratin 18 for Progressive Types of Nonalcoholic Fatty Liver Disease.

We aimed to evaluate whether composite blood biomarkers including aldo-keto reductase family 1 member B10 (AKR1B10) and cytokeratin 18 (CK-18; a nonalcoholic steatohepatitis [NASH] marker) have clinically applicable performance for the diagnosis of NASH, advanced liver fibrosis, and high-risk NASH (NASH+significant fibrosis). A total of 116 subjects including healthy control subjects and patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were analyzed to assess composite blood-based and imaging-based biomarkers either singly or in combination. A composite blood biomarker comprised of AKR1B10, CK-18, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) showed excellent performance for the diagnosis of, NASH, advanced fibrosis, and high-risk NASH, with area under the receiver operating characteristic curve values of 0.934 (95% confidence interval [CI], 0.888 to 0.981), 0.902 (95% CI, 0.832 to 0.971), and 0.918 (95% CI, 0.862 to 0.974), respectively. However, the performance of this blood composite biomarker was inferior to that various magnetic resonance (MR)-based composite biomarkers, such as proton density fat fraction/MR elastography- liver stiffness measurement (MRE-LSM)/ALT/AST for NASH, MRE-LSM+fibrosis-4 index for advanced fibrosis, and the known MR imaging-AST (MAST) score for high-risk NASH. Our blood composite biomarker can be useful to distinguish progressive forms of NAFLD as an initial noninvasive test when MR-based tools are not available.

Serum Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) as a Potential Biomarker for Diagnosis of Hepatocellular Carcinoma.

To evaluate the diagnostic performance of aldo-keto reductase family 1 member B10 (AKR1B10) in a Beijing cohort with hepatocellular carcinoma (HCC). This study included 521 subjects who visited Peking Union Medical College Hospital from June 2017 to May 2023, including 109 cases of HCC, 165 cases of healthy controls, 106 cases of benign liver diseases, and 141 cases of other cancers. Serum AKR1B10 levels were measured and compared across various groups. Diagnostic performances of serum AKR1B10 and other tumor markers were assessed using receiver operator characteristic (ROC) curves. In addition, a subset of HCC patients who underwent surgical resection were recruited for clinical follow-up study. We found that serum AKR1B10 expression was higher in patients with HCC relative to other control groups. The association between serum AKR1B10 and clinical features of HCC was not observed. Serum AKR1B10 showed a high diagnostic performance for HCC, and when combined with AFP, the diagnostic effectiveness was significantly improved. Specifically, serum AKR1B10 showed superior diagnostic effectiveness for AFP-negative HCC. The clinical follow-up study indicated a gradual decrease in serum AKR1B10 after surgery. Our study demonstrated that serum AKR1B10 is a promising biomarker for HCC, and when used in combination with AFP can significantly improve the detection rate of HCC.

Computational Insight and Anticancer Effect of Cinnamic Acid-Derivative Amide Compounds

In this research, a meticulous screening process was conducted using four servers: Drug Target Explorer, Swiss Target Predictor, SEA Predictor, and Target Hunter. The primary objective was to identify a series of potential biological targets related to the regulation of cell growth and apoptosis in cancer cells using cinnamic acid derivatives. This study focused on five specific targets, matrix metallopeptidase 9 (MMP9), apoptosis inducing factor (AIF), aldo-keto reductase family 1 member C3 (AKR1C3), aldo-keto reductase family 1 member B10 (AKR1B10), mitogenactivated protein kinase 14 (MAPK14), all of which are well known to play a significant role in cancer cell dynamics. To explore both molecular recognition and molecular dynamics, a series of in silico investigations (docking and molecular dynamics) were carried out using a collection of 14 cinnamic acid derivatives, including cinnamic acid phenethyl ester (CAPE) as a notable reference molecule due to its widely recognized anticancer effects. Furthermore, preliminary in vitro data revealed a potentially promising cytotoxic effect of (E)-N-[(3,4-dichlorophenyl)methyl]- 3-(4-phenoxyphenyl)-2-propenamide (LQM755) on a human gastric adenocarcinoma cell-line (AGS cells), which are characterized by the overexpression of the MMP9 protein. Therefore, the chemical compound LQM755 provides an initial perspective in the field of cancer therapy.

AKR1B10 inhibits the proliferation and metastasis of hepatocellular carcinoma cells by regulating the PI3K/AKT pathway.

Hepatocellular carcinoma (HCC) is one of the most frequent and aggressive malignant neoplasms, and is associated with a poor prognosis. Therefore, there is a crucial need to develop novel cancer therapies and identify novel therapeutic targets. Aldo-keto reductase family 1 member B10 (AKR1B10) is expressed in various types of cancer. However, the role of AKR1B10 in the pathological process of HCC and its underlying molecular mechanism is poorly understood. AKR1B10 expression was evaluated pan-cancer and in HCC using the Genomic Data Commons-The Cancer Genome Atlas (GDC-TCGA) and International Cancer Genome Consortium (ICGC) databases. The relationship between elevated AKR1B10 expression and overall survival in HCC patients was analyzed using a Kaplan-Meier plot. The effects of AKR1B10 on the proliferation, migration, and invasion of HCC cells were evaluated. The proliferation of HCC was measured using CCK-8 and colony formation assays. Transwell and wound healing assays were used to assess the migration and invasion of HCC cells. Western blots were used to detect the expression of proliferative and epithelial-mesenchymal transition (EMT) related proteins in HCC cells, including CCND1, E-cadherin, N-cadherin, vimentin, Twist1, PI3K/p-PI3K, and AKT/p-AKT. AKR1B10 expression was significantly upregulated pan-cancer and in liver cancer. Upregulated AKR1B10 expression was associated with a worse overall survival. HCC cell proliferation, migration, and invasion were found to be influenced by AKR1B10 activity, as demonstrated using DepMap analysis. AKR1B10 knockdown in Huh7 cells reduced proliferation, migration, invasion, and EMT. Mechanistically, AKR1B10 increased the expression of proliferative and EMT-related proteins CCND1, E-cadherin, N-cadherin, vimentin, and Twist1. PI3K and AKT phosphorylation levels decreased following AKR1B10 knockdown. In conclusion, AKR1B10 promoted the proliferation, migration, and invasion of HCC cells via the PI3K/AKT signaling pathway, a potential prognostic indicator.

AKR1B10 regulates M2 macrophage polarization to promote the malignant phenotype of gastric cancer.

Immunotherapy has brought new hope to gastric cancer (GC) patients. Exploring the immune infiltration pattern in GC and the key molecules is critical for optimizing the efficacy of immunotherapy. Aldo-keto reductase family 1 member B10 (AKR1B10) is an inflammatory regulator and is closely related to the prognosis of patients with GC. However, the function of AKR1B10 in GC remains unclear. In the present study, the CIBERSORT algorithm was used to analyze the immune infiltration pattern in 373 samples in the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were seared by combing the TCGA database and the Gene Expression Omnibus (GEO) database, and the key molecule AKR1B10 was identified by weighted gene coexpression network analysis (WGCNA). The biological functions of AKR1B10 in stomach adenocarcinoma (STAD) were investigated in vitro. Macrophage polarization was the main immune infiltration pattern in GC, and the state of macrophage polarization was closely related to the pathological grading of GC and the clinical stage of patients. AKR1B10, MUC5AC, TFF2, GKN1, and PGC were significantly down-regulated in GC tissues. Low AKR1B10 expression induced M2 macrophage polarization and promoted the malignant phenotype of GC. M2 macrophage polarization is the main immune infiltration pattern in GC. Low AKR1B10 expression induces M2 macrophage polarization and promotes the malignant transformation of GC.

Diagnostic value of aldo‑keto reductase family 1 member B10 in human nasopharyngeal carcinoma.

Aldo-keto reductase family 1 member B10 (AKR1B10) is a potential marker of several types of cancer; however, the role of AKR1B10 in nasopharyngeal carcinoma (NPC) remains unclear. In the present study, AKR1B10 RNA-seq data and clinical information were obtained from The Cancer Genome Atlas head and neck squamous cell carcinoma (HNSCC) database to evaluate the role of AKR1B10 in HNSCC. There was no statistically significant difference in the expression of AKR1B10 between HNSCC tissues and adjacent normal tissues, and high AKR1B10 expression was not associated with poor overall survival according to the public database. The present study further examined the role of AKR1B10 in patients with NPC using data obtained from the Gene Expression Omnibus database. Analysis of the GSE53819 and GSE61218 datasets showed that the there were no significant differences in the expression levels of AKR1B10 between NPC tissues and normal tissues. However, analysis of the GSE103611 dataset indicated that AKR1B10 may be associated with distance metastasis following radical treatment in NPC. Finally, serum samples from patients with NPC and healthy controls were collected and analyzed. The results revealed that AKR1B10 levels were significantly increased in samples from patients with NPC compared with those from healthy controls, and the area under the receiver operating characteristic curve was 0.909. In conclusion, unlike tissue AKR1B10 expression, serum AKR1B10 levels may be a promising biomarker for the diagnosis of NPC.

Aldo-keto reductase family 1 member B10 is regulated by nucleos(t)ide analogues for chronic hepatitis B

The number of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients persists even under nucleos(t)ide analogues (NAs) treatment. Aldo-keto reductase family 1 member B10 (AKR1B10) expression has been reported in advanced chronic liver diseases as well as cancer tissues. We observed an association between related to HCC incidence and serum AKR1B10 by analyzing patients under treatment with NAs. Serum AKR1B10 levels measured by ELISA were higher in HCC cases under NA treatment compared with non-HCC cases and were associated with lamivudine- and adefovir pivoxil-, but not entecavir- or tenofovir alafenamide-treated cases. The latter drugs did not increase AKR1B10 values even in HCC cases, suggesting that they influence the reduction of AKR1B10 in any cases. This analysis was supported by in-vitro examination, which showed reduced AKR1B10 expression by entecavir and tenofovir via immunofluorescence staining. In conclusion there was a relationship between HBV-related HCC incidence and AKR1B10 under nucleos(t)ide analogues, especially in the use of lamivudine and adefovir pivoxil, but entecavir and tenofovir had suppressive effects of AKR1B10.

95-OR: A New Composite Blood Biomarker Performs Well in the Diagnosis of NASH, Advanced Hepatic Fibrosis, and High-Risk NASH

Background and Aims: Plasma aldo-keto reductase family 1 member B10 (AKR1B10) well reflects the progression of NAFLD. Thus, we aimed to evaluate whether composite blood biomarkers including AKR1B10 and cytokeratin 18 (CK-18) have acceptable for the diagnosis NASH, advanced liver fibrosis, and high-risk NASH (NASH + significant fibrosis), respectively. Methods: A total of 116 subjects in our pooled cohort (24 healthy controls and 92 patients with biopsy-proven NAFLD (48 patients with NAFL and 44 patients with NASH) were analysed to assess composite blood-based and imaging-based biomarkers, which included the markers below either singly or in combination: AKR1B10, CK-18, AST, ALT, enhanced liver fibrosis (ELF) score, FIB-4, proton density fat fraction (MRI-PDFF), MR elastography-liver stiffness measurement (MRE-LSM), and the known MRI-AST (MAST) and FibroScan-AST (FAST) scores Results: Composite blood biomarker comprised of AKR1B10, CK-18, AST, and ALT showed excellent performance for the diagnosis of, NASH, advanced fibrosis, and high-risk NASH, with AUROC curve values of 0.934 (95% CI: 0.888-0.981), 0.902 (95% CI 0.832-0.971) and 0.918 (95% CI 0.862-0.974), respectively. However, the performances of this blood composite biomarker were all inferior to various MR-based composite biomarkers (MRI-PDFF/MRE-LSM/ALT/AST for NASH, AUROC = 0.964; MRE-LSM + FIB-4 for advanced fibrosis, AUROC=0.982; and the MAST score for high-risk NASH, AUROC=0.947), with a better performance than the FAST score (AUROC=0.909) for the diagnosis of high-risk NASH. Conclusion: Although slightly inferior to the MR imaging-based composite biomarkers, blood composite biomarker composed of AKR1B10, CK-18, AST, and ALT showed excellent performance in the diagnosis of progressive forms of NAFLD. Disclosure D.Lee: None.

Impact of cytotoxic chemotherapy on aldo-keto reductase family 1 member B10 expression.

Aldo-keto reductase family 1 member B10 (AKR1B10) is a protein that is produced and secreted by a significant number of breast cancers. However, a potential confounder to the use of AKR1B10 as a tumor marker is its elevation in patients given cytotoxic chemotherapy. We therefore conducted a prospective study to analyze AKR1B10 levels in patients with breast cancer receiving neoadjuvant cytotoxic chemotherapy. The study enrolled 10 patients from November 2015 to July 2017. All patients had locally advanced, but non-metastatic, breast cancer, and they received neoadjuvant chemotherapy followed by surgery. Serum AKR1B10 levels and tumor imaging were assessed before, during, and after chemotherapy. No increase in serum AKR1B10 levels was noted in patients receiving chemotherapy whose levels were elevated at diagnosis. The findings are complex, but the overall data suggest that AKR1B10 is suitable as a tumor marker in patients with elevated levels at the time of diagnosis.

FNDC5 and AKR1B10 inhibit the proliferation and metastasis of adrenocortical carcinoma cells by regulating AMPK/mTOR pathway.

Being a rare malignancy, adrenocortical carcinoma (ACC) exhibits aggressiveness and poor prognosis. Fibronectin type III domain-containing protein 5 (FNDC5) is a transmembrane protein involved in multiple types of cancer. Aldo-keto reductase family 1 member B10 (AKR1B10) has a suppressive role in ACC. The present study aimed to investigate the role of FNDC5 in ACC cells as well as its mechanisms related to AKR1B10. The Gene Expression Profiling Interactive Analysis database predicted FNDC5 expression in tumour tissue of patients suffering from ACC and the overall survival rate. Western blotting as well as reverse transcription-quantitative PCR were used for the examination of the transfection efficiency of FNDC5-overexpression vector (Oe-FNDC5) and small interfering (si)RNA against AKR1B10. Cell Counting Kit-8 was employed for the assessment of cell viability. The proliferation, migration and invasion of the transfected cells were assessed by 5-ethynyl-2'-deoxyuridine staining, wound healing and Transwell assays. Additionally, cell apoptosis was evaluated by flow cytometry and caspase-3 activity was determined by ELISA. The levels of epithelial-mesenchymal transition- and 5'-AMP-activated protein kinase (AMPK)/mTOR signalling pathway-associated proteins were assessed by western blotting. The interaction between FNDC5 and AKR1B10 was confirmed by co-immunoprecipitation. FNDC5 levels in ACC tissue were reduced compared with normal tissue. After overexpressing FNDC5, proliferation, migration and invasion of NCI-H295R cells were suppressed, while cell apoptosis was promoted. FNDC5 interacted with AKR1B10 and AKR1B10 knockdown promoted proliferation, migration and invasion while inhibiting the apoptosis of NCI-H295R cells transfected with si-AKR1B10. The AMPK/mTOR signalling pathway was activated by FNDC5 overexpression, which was subsequently suppressed by AKR1B10 knockdown. Collectively, FNDC5 overexpression inhibited proliferation, migration and invasion while promoting apoptosis of NCI-H295R cells via triggering the AMPK/mTOR signalling pathway. These effects were counteracted by AKR1B10 knockdown.

Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation.

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that eventually progresses to cirrhosis and hepatocellular carcinoma (HCC) in the absence of proper treatment. However, Gene expression and molecular mechanisms involved in the pathogenesis of PBC have not been completely elucidated. Methods: Microarray expression profiling dataset GSE61260 was downloaded from the Gene Expression Omnibus (GEO) database. Data were normalized to screen differentially expressed genes (DEGs) using the limma package in R. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed to identify hub genes and an integrative regulatory network of transcriptional factor-DEG-microRNA was established. Gene Set Enrichment Analysis (GSEA) was used to analyze differences in biological states for groups with different expressions of aldo-keto reductase family 1 member B10 (AKR1B10). Immunohistochemistry (IHC) analysis was performed to validate the expression of hepatic AKR1B10 in patients with PBC. The association of hepatic AKR1B10 levels with clinical parameters was evaluated using one-way analysis of variance (ANOVA) and Pearson's correlation analysis. Results: This study identified 22 upregulated and 12 downregulated DEGs between patients with PBC and healthy controls. GO and KEGG analysis revealed that DEGs were mainly enriched in immune reactions. AKR1B10 was identified as a key gene and was further analyzed by screening out hub genes from the PPI network. GSEA analysis indicated that high expression of AKR1B10 might promote PBC to develop into HCC. Immunohistochemistry results verified the increased expression of hepatic AKR1B10 in patients with PBC and demonstrated its positive correlation with the severity of PBC. Conclusion: AKR1B10 was identified as a hub gene in PBC by integrated bioinformatics analysis and clinical validation. The increase of AKR1B10 expression in patients with PBC was associated with disease severity and might promote the progression of PBC to HCC.

Clinical value of AKR1B10 in hepatocellular carcinoma: A systematic review and meta-analysis.

To evaluate the clinical value of Aldo-keto reductase family 1 member B10 (AKR1B10) in the diagnosis and prognosis of hepatocellular carcinoma (HCC). A search of the PubMed, China Biology Medicine, Cochrane, and Embase databases was performed to conduct meta-analyses to evaluate the accuracy of AKR1B10 in diagnosing HCC and to assess the impact on prognosis of patients after curative resection of HCC. A total of 12 different cohorts from 11 studies including 2747 HCC patients and 2053 controls showed that the pooled specificity and the pooled sensitivity of AKR1B10 for the diagnosis of HCC were 0.78 (95% CI: 0.69-0.85) and 0.85 (95% CI: 0.77-0.90), respectively. The pooled sensitivity and specificity of serum AKR1B10 for the diagnosis of HCC were 0.80 (95% CI: 0.70-0.86) and 0.87 (95% CI: 0.77-0.93), respectively. The pooled sensitivity and specificity of AKR1B10 in malignant tumor tissue for the diagnosis of HCC were 0.78 (95% CI: 0.61-0.89) and 0.82 (95% CI: 0.69-0.90), respectively. The pooled sensitivity and specificity of AKR1B10 to distinguish HCC from benign liver disease were 0.71 (95% CI: 0.62-0.78) and 0.84 (95% CI: 0.77-0.89), respectively. The sensitivity and specificity of AKR1B10 combined with alpha fetoprotein (AFP) in the diagnosis of HCC were 0.84 (95% CI: 0.79-0.88) and 0.88 (95% CI: 0.73-0.95), respectively. The pooled sensitivity and specificity of AKR1B10 in malignant tumor tissue for the diagnosis of early-stage HCC were 0.85 (95% CI: 0.62-0.95) and 0.88 (95% CI: 0.81-0.93), respectively. A meta-analysis of five studies including 798 patients demonstrated that high AKR1B10 expression in liver malignant tumor was associated with better overall survival in patients with HCC after hepatectomy (HR = 0.54, 95% CI: 0.41-0.72, p < 0.001). AKR1B10 exhibits a great clinical value in the diagnosis of HCC, especially for early-stage HCC, with excellent diagnostic accuracy. Furthermore, AKR1B10 expression can predict the prognosis of HCC patients after hepatic resection.

LncRNA 1700020I14Rik promotes AKR1B10 expression and activates Erk pathway to induce hepatocyte damage in alcoholic hepatitis

Alcoholic hepatitis (AH), a kind of alcoholic liver disease, shows poor prognosis. Long noncoding RNAs (lncRNAs) exert critical role in liver diseases. Here, we intended to investigate the possible molecular mechanism that 1700020I14Rik-based regulation of microRNA (miR)-137/Aldo-keto reductase family 1 member B10 (AKR1B10) affecting the inflammatory response and hepatocyte damage in AH. AH-related genes and the down-stream regulatory pathway were screnned by bioinformatics. Mouse normal hepatocyte cell line AML12 was selected to construct an ethanol-induced hepatocyte injury model for in vitro mechanistic validation, while we also established an AH mouse model using the ethanol with gradually increased concentration of 2–4% (v/v) for in vivo study. Specific role of 1700020I14Rik/miR-137/AKR1B10 in AML12 cell viability, proliferation and apoptotic capacity as well as inflammation and liver damage in mice were analyzed following ectopic and depletion approaches. We found elevated AKR1B10 and 1700020I14Rik but reduced miR-137 in AH. 1700020I14Rik was able to elevated miR-137-mediated AKR1B10. In vitro cell experiments and in vivo animal experiments validated that 1700020I14Rik reduced ethanol-induced hepatocyte damage and inflammation in AH mice through regulation of miR-137–mediated AKR1B10/Erk axis. The current study underlied that 1700020I14Rik could activate AKR1B10/Erk signaling through inhibition of miR-137, thereby promoting the hepatocyte damage in AH mice.

Plasma Aldo-Keto Reductase Family 1 Member B10 as a Biomarker Performs Well in the Diagnosis of Nonalcoholic Steatohepatitis and Fibrosis

We found several blood biomarkers through computational secretome analyses, including aldo-keto reductase family 1 member B10 (AKR1B10), which reflected the progression of nonalcoholic fatty liver disease (NAFLD). After confirming that hepatic AKR1B10 reflected the progression of NAFLD in a subgroup with NAFLD, we evaluated the diagnostic accuracy of plasma AKR1B10 and other biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis in replication cohort. We enrolled healthy control subjects and patients with biopsy-proven NAFLD (n = 102) and evaluated the performance of various diagnostic markers. Plasma AKR1B10 performed well in the diagnosis of NASH with an area under the receiver operating characteristic (AUROC) curve of 0.834 and a cutoff value of 1078.2 pg/mL, as well as advanced fibrosis (AUROC curve value of 0.914 and cutoff level 1078.2 pg/mL), with further improvement in combination with C3. When we monitored a subgroup of obese patients who underwent bariatric surgery (n = 35), plasma AKR1B10 decreased dramatically, and 40.0% of patients with NASH at baseline showed a decrease in plasma AKR1B10 levels to below the cutoff level after the surgery. In an independent validation study, we proved that plasma AKR1B10 was a specific biomarker of NAFLD progression across varying degrees of renal dysfunction. Despite perfect correlation between plasma and serum levels of AKR1B10 in paired sample analysis, its serum level was 1.4-fold higher than that in plasma. Plasma AKR1B10 alone and in combination with C3 could be a useful noninvasive biomarker for the diagnosis of NASH and hepatic fibrosis.

Role of AKR1B10 and AKR1B8 in the pathogenesis of non-alcoholic steatohepatitis (NASH) in mouse.

Non-alcoholic steatohepatitis (NASH) is a clinically important spectrum of non-alcoholic fatty liver disease (NAFLD) in humans. NASH is a stage of NAFLD progression wherein liver steatosis accompanies inflammation and pro-fibrotic events. Presently, there are no approved drugs for NASH, which has become a leading cause of liver transplant worldwide. To discover novel drug targets for NASH, we analyzed a human transcriptomic NASH dataset and found Aldo-keto reductase family 1 member B10 (AKR1B10) as a significantly upregulated gene in livers of human NASH patients. Similarly murine Akr1b10 and Aldo-keto reductase family 1 member B8 (Akr1b8) gene, which is a murine ortholog of human AKR1B10, were also found to be upregulated in a mouse model of diet-induced NASH. Furthermore, pharmacological inhibitors of AKR1B10 significantly reduced the pathological features of NASH such as steatosis, inflammation and fibrosis in mouse. In addition, genetic silencing of both mouse Akr1b10 and Akr1b8 significantly reduced the expression of proinflammatory cytokines from hepatocytes. These results, thus, underscore the involvement of murine AKR1B10 and AKR1B8 in the pathogenesis of murine NASH and raise an intriguing possibility of a similar role of AKR1B10 in human NASH.

Aldehyde Dehydrogenase 2 Family Member (ALDH2) Is a Therapeutic Index for Oxaliplatin Response on Colorectal Cancer Therapy with Dysfunction p53.

Oxaliplatin resistance is a major issue in the treatment of p53 mutant colorectal cancer (CRC). Finding the specific biomarkers would improve therapeutic efficacy of patients with CRC. In order to figure out the biomarker for CRC patients with mutant p53 access oxaliplatin, a Gene Expression Omnibus dataset (GSE42387) was used to determine differentially expressed genes (DEGs). The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software were used to predict protein-protein interactions. The Database for Annotation, Visualization, and Integrated Discovery online tool was used to group the DEGs into their common pathways. 138 DEGs were identified with 46 upregulated and 92 downregulated. In the PPI networks, 7 of the upregulated genes and 13 of the downregulated genes were identified as hub genes (high degrees). Four hub genes, aldehyde dehydrogenase 2 family member (ALDH2), aldo-keto reductase family 1 member B1 (AKR1B1), aldo-keto reductase family 1 member B10 (AKR1B10), and monoglyceride lipase (MGLL) were enriched in the most significant pathway, glycerolipid metabolism. Further, we found that low expression of ALDH2 is correlated with poor overall survival and oxaliplatin resistance. Finally, we found that combined treatment with ALDH2 inhibitor and oxaliplatin will reduce the sensitivity to oxaliplatin in p53 mutant HT29 cells. In conclusion, we demonstrate that ALDH2 may be a biomarker for oxaliplatin resistance status in CRC patients and bring new insight into treatment strategy for p53 mutant CRC patients.

Predictive Role for Serum Aldo-Keto Reductase Family1 Member B10 for Early Detection of Hepatocellular Carcinoma in Egyptian Patients

Background: Most patients with hepatocellular carcinoma (HCC) are diagnosed at late stages despite of improvement screening programs and lack of effective diagnostic methods for cases with preclinical HCC leads to a low rate of early detection. Aldo-keto reductase family 1 member B10 (AKR1B10) is associated with several types of cancer. However, to our knowledge, the diagnostic significance of AKR1B10 measurement in early stage of HCC has poorly understood.&#x0D; Aim&#x0D; To evaluate the diagnostic performance of serum AKR1B10 in hepatitis C virus (HCV)-related liver disorders and its unique role in diagnosing HCC.&#x0D; Methods&#x0D; Serum AKR1B10 was detected by sandwich ELISA in 30 patients with HCV-related HCC, 30 patients with HCV related liver cirrhosis, and 20 healthy controls. Both Serum AKR1B10 and α-fetoprotein (AFP) levels were analyzed, evaluated and compared.&#x0D; Results&#x0D; Serum AKR1B10 was significantly elevated in patients with HCC compared with. The sensitivity (86.7.0%) and specificity (70%) for HCC diagnosis with AKR1B10 were high at a cutoff value of 0.945 ng/ml, while alpha fetoprotein had sensitivity 67% and specificity 88% in early detection of HCC among studied groups at cutoff point higher than 17.9. ng/ml. Furthermore, concurrent measurement of Alpha fetoprotein and AKR1B10 had increased sensitivity to 97.6% and specificity 100% in early detection of HCC among studied groups at cutoff point higher than ≥150 ng/ml. Furthermore, concurrent measurement of serum AKR1B10 and AFP significantly increased sensitivity and negative predictive value for HCC diagnosis.&#x0D; Conclusions&#x0D; we concluded in the current study that AKR1B10 has a unique role as a biomarker for early-stage HCV-related HCC. Compared with AFP alone, a combination of serum AKR1B10 and AFP had an increased the diagnostic performance in patients with HCC.

AKR1B10 inhibits the proliferation and migration of gastric cancer via regulating epithelial-mesenchymal transition.

Gastric cancer (GC) is a common malignancy around the world with a poor prognosis. Aldo-keto reductase family 1 member B10 (AKR1B10) is indispensable to cancer development and progression, which has served as a diagnostic biomarker for tumors. In our study, we demonstrated that the expression of AKR1B10 in GC tissues was significantly lower compared with normal gastric tissues. Subgroup analysis showed that, according to the clinic-pathological factors, the effect of the AKR1B10 expression level on the prognosis of GC patients was significantly different. Moreover, reduced expression of AKR1B10 promoted the ability of GC cells in proliferation and migration. Furthermore, increased AKR1B10 levels resulted in the opposite trend in vitro. Moreover, AKR1B10 was correlated with epithelial-mesenchymal transition (EMT) in a significant way. In vivo experiment, knockdown of AKR1B10 promoted the growth of tumor, increased Vimentin, and E-cadherin significantly. In summary, AKR1B10 is considered as a tumor suppressor in GC and is a promising therapeutic target.

AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-\u03baB signaling pathway

BackgroundAberrant expression of Aldo-Keto reductase family 1 member B10 (AKR1B10) was associated with tumor size and metastasis of breast cancer in our published preliminary studies. However, little is known about the detailed function and underlying molecular mechanism of AKR1B10 in the pathological process of breast cancer.MethodsThe relationship between elevated AKR1B10 expression and the overall survival and disease-free survival of breast cancer patients was analyzed by Kaplan–Meier Plotter database. Breast cancer cell lines overexpressing AKR1B10 (MCF-7/AKR1B10) and breast cancer cell lines with knockdown of AKR1B10 (BT-20/shAKR1B10) were constructed to analyze the impact of AKR1B10 expression on cell proliferation and migration of breast cancer. The expression levels of AKR1B10 were detected and compared in the breast cancer cell lines and tissues by RT-qPCR, western blot and immunohistochemistry. The proliferation of breast cancer cells was monitored by CCK8 cell proliferation assay, and the migration and invasion of breast cancer cells was observed by cell scratch test and transwell assay. The proliferation- and EMT-related proteins including cyclinD1, c-myc, Survivin, Twist, SNAI1, SLUG, ZEB1, E-cadherin, PI3K, p-PI3K, AKT, p-AKT, IKBα, p-IKBα, NF-κB p65, p-NF-κB p65 were detected by western blot in breast cancer cells. MCF-7/AKR1B10 cells were treated with LY294002, a PI3K inhibitor, to consider the impact of AKR1B10 overexpression on the PI3K/AKT/NF-κB signal cascade and the presence of NF-κB p65 in nuclear. In vivo tumor xenograft experiments were used to observe the role of AKR1B10 in breast cancer growth in mice.ResultsAKR1B10 expression was significantly greater in breast cancer tissue compared to paired non-cancerous tissue. The expression of AKR1B10 positively correlated with lymph node metastasis, tumor size, Ki67 expression, and p53 expression, but inversely correlated with overall and disease-free survival rates. Gene Ontology analysis showed that AKR1B10 activity contributes to cell proliferation. Overexpression of AKR1B10 facilitated the proliferation of MCF-7 cells, and induced the migration and invasion of MCF-7 cells in vitro in association with induction of epithelial-mesenchymal transition (EMT). Conversely, knockdown of AKR1B10 inhibited these effects in BT-20 cells. Mechanistically, AKR1B10 activated PI3K, AKT, and NF-κB p65, and induced nuclear translocation of NF-κB p65, and expression of proliferation-related proteins including c-myc, cyclinD1, Survivin, and EMT-related proteins including ZEB1, SLUG, Twist, but downregulated E-cadherin expression in MCF-7 cells. AKR1B10 silencing reduced the phosphorylation of PI3K, AKT, and NF-κB p65, the nuclear translocation of NF-κB p65, and the expression of proliferation- and migration-related proteins in BT-20 cells. LY294002, a PI3K inhibitor, attenuated the phosphorylation of PI3K, AKT, and NF-κB p65, and the nuclear translocation of NF-κB p65. In vivo tumor xenograft experiments confirmed that AKR1B10 promoted breast cancer growth in mice.ConclusionsAKR1B10 promotes the proliferation, migration and invasion of breast cancer cells via the PI3K/AKT/NF-κB signaling pathway and represents a novel prognostic indicator as well as a potential therapeutic target in breast cancer.

AKR1B10 expression in benign prostatic hyperplasia and its related mechanism.

The aim of the present study was to investigate the expression of aldo-keto reductase family 1 member B10 (AKR1B10) in benign prostatic hyperplasia (BPH) and its related mechanism. In total, 142 BPH patients admitted from March 2017 to March 2019 at the First Hospital of Hunan University of Chinese Medicine and 140 healthy people undergoing physical examination were selected as the research subjects. The clinical value of AKR1B10 in BPH was analyzed. Twenty clean SD rats were selected, and 10 were selected to establish the prostate hyperplasia model, while the remaining 10 were set as the control group. Ten days after the model was established, AKR1B10 and NF-κB expression in prostate tissues of rats in both groups was detected by PCR and immunohistochemistry. The primary cells in prostate hyperplasia were cultured, and then they were transfected with AKR1B10 to observe the changes of cell biological behavior. AKR1B10 and NF-κB mRNA significantly increased in peripheral blood of BPH patients and prostate tissue of BPH model rats (P<0.001), and AKR1B10 had good diagnostic value for BPH (P<0.001). In addition, it was positively correlated with PSA, EGF, IL-6 and TNF-α (P<0.001). After transfection with AKR1B10-inhibitor, it was revealed that the proliferation of prostate hyperplasia cells decreased, while the apoptosis of prostate hyperplasia cells increased and the NF-κB protein expression decreased (P<0.001). Collectively, high expression of AKR1B10 in BPH promoted the proliferation of prostate cells and reduced their apoptosis, and the mechanism may be through regulation of NF-κB.