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Background and Aim: The biological functions and clinical implications of lysophosphatidylcholine acyltransferase 1 (LPCAT1) remain unclarified in gastric cancer (GC). The aim of the current study was to explore the possible clinicopathological significance of LPCAT1 and its perspective mechanism in GC tissues. Materials and Methods: The protein expression and mRNA levels of LPCAT1 were detected from in‐house immunohistochemistry and public high‐throughput RNA arrays and RNA sequencing. To have a comprehensive understanding of the clinical value of LPCAT1 in GC, all enrolled data were integrated to calculate the expression difference and standard mean difference (SMD). The biological mechanism of LPCAT1 in GC was confirmed by computational biology and in vitro experiments. Migration and invasion assays were also conducted to confirm the effect of LPCAT1 in GC. Results: Both protein and mRNA expression levels of LPCAT1 in GC were remarkably higher than those in noncancerous controls. Comprehensively, the SMD of LPCAT1 mRNA was 1.11 (95% CI = 0.86–1.36) in GC, and the summarized AUC was 0.85 based on 15 datasets containing 1727 cases of GC and 940 cases of non‐GC controls. Moreover, LPCAT1 could accelerate the invasion and migration of GC by boosting the neutrophil degranulation pathway and disturbing the immune microenvironment. Conclusion: An increased level of LPCAT1 may promote the progression of GC. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is a common cancer worldwide with a high prevalence. This study was conducted to elucidate the expression and clinical significance of Sorbin and SH3 domain‐containing protein 1 (SORBS1) in BC as well as to explore its molecular mechanism in BC tumourigenesis. RNA‐sequencing data, microarray, and Immunohistochemistry (IHC) were applied to elucidated the SORBS1 expression at multiple levels. After that, the relationship between tumour‐immune infiltration and SORBS1 was also explored. Finally, SORBS1‐related genes in BC were identified to perform functional enrichment analyses. The expression integration revealed that the comprehensive expression of SORBS1 at the mRNA level was −1.02 and that at the protein level was −3.73, based on 12 platforms, including 1221 BC and 187 non‐BC samples. SORBS1 was negatively correlated with tumour purity (correlation = −0.342, p < 0.001) and positively correlated with macrophage (correlation = 0.358, p < 0.001). The results of enrichment analyses revealed that the most significant biological pathways of SORBS1‐related genes were epithelial‐mesenchymal transition. SORBS1 was significantly down‐regulated in BC and may play a role as tumour suppressor. This study provides new directions and biomarkers for future BC diagnosis. [ABSTRACT FROM AUTHOR]

Despite great advance has been made in multi‐modality treatments for HCC patients, the effectiveness is far from satisfactory with worse survival outcome, which may be partly explainable by the anti‐tumor deficiency of the immune system. It is necessary to clarify the molecular mechanism of HCC immunodeficiency. Here, we demonstrated that carbohydrate sulfotransferase 11 (CHST11) was upregulated in HCC and related to advanced TNM stage. HCC patients with TP53 mutation showed higher CHST11 expression. Survival analysis revealed that CHST11 was an independent prognostic biomarker in HCC. Cellular functional experiments indicated that knockdown of CHST11 in HCC inhibited cell proliferation and metastasis. Gene functional enrichment analyses indicated that CHST11 modulated pathways related to tumor growth, metastasis and immune regulation. Continuative immune‐related analyses revealed that CHST11 expression facilitated Tregs infiltration in HCC and promoted the expression of checkpoints PD‐L1/PD‐1, resulting in the immunosuppression of HCC. Targeting CHST11 may inhibit Tregs infiltration and enhance the antineoplastic effect of immune checkpoint inhibitors, which provides a novel insight into the combination immunotherapy with Treg‐modulating agents and PD‐L1/PD‐1 inhibitors. [ABSTRACT FROM AUTHOR]

Stromal antigen 1 (STAG1), a component of cohesion, is overexpressed in various cancers, but it is unclear whether it has a role in the transcriptional regulation of hepatocellular carcinoma (HCC). To test this hypothesis, here, we screened global HCC datasets and performed multiscale embedded gene co‐expression network analysis to identify the potential functional modules of differentially expressed STAG1 co‐expressed genes. The putative transcriptional targets of STAG1 were identified using chromatin immunoprecipitation followed by high‐throughput DNA sequencing. The cohesin‐associated gene score (CAGS) was quantified using the The Cancer Genome Atlas HCC cohort and single‐sample gene set enrichment analysis. Distinct cohesin‐associated gene patterns were identified by calculating the euclidean distance of each patient. We assessed the potential ability of the CAGS in predicting immune checkpoint blockade (ICB) treatment response using IMvigor210 and GSE78220 cohorts. STAG1 was upregulated in 3313 HCC tissue samples compared with 2692 normal liver tissue samples (standard mean difference = 0.54). A total of three cohesin‐associated gene patterns were identified, where cluster 2 had a high TP53 mutated rate and a poor survival outcome. Low CAGS predicted a significant survival advantage but presaged poor immunotherapy response. Differentially expressed STAG1 co‐expression genes were enriched in the mitotic cell cycle, lymphocyte activation, and blood vessel development. PDS5A and PDGFRA were predicted as the downstream transcriptional targets of STAG1. In summary, STAG1 is significantly upregulated in global HCC tissue samples and may participate in blood vessel development and the mitotic cell cycle. A cohesin‐associated gene scoring system may have potential to predict the ICB response. [ABSTRACT FROM AUTHOR]

Basing on alternative splicing events (ASEs) databases, the authors herein aim to explore potential prognostic biomarkers for cervical squamous cell carcinoma (CESC). mRNA expression profiles and relevant clinical data of 223 patients with CESC were obtained from The Cancer Genome Atlas (TCGA). Correlated genes, ASEs and percent‐splice‐in (PSI) were downloaded from SpliceSeq, respectively. The PSI values of survival‐associated alternative splicing events (SASEs) were used to construct the basis of a prognostic index (PI). A protein–protein interaction (PPI) network of genes related to SASEs was generated by STRING and analysed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Consequently, 41,776 ASEs were discovered in 19,724 genes, 2596 of which linked with 3669 SASEs. The PPI network of SASEs related genes revealed that TP53 and UBA52 were core genes. The low‐risk group had a longer survival period than high‐risk counterparts, both groups being defined according to PI constructed upon the top 20 splicing events or PI on the overall splicing events. The AUC value of ROC reached up to 0.88, demonstrating the prognostic potential of PI in CESC. These findings suggested that ASEs involve in the pathogenesis of CESC and may serve as promising prognostic biomarkers for this female malignancy. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide and tends to be detected at an advanced stage. More effective biomarkers for HCC screening and prognosis assessment are needed and the mechanisms of HCC require further exploration. The role of MAOA in HCC has not been intensively investigated. Methods: In‐house tissue microarrays, genechips, and RNAsequencing datasets were integrated to explore the expression status and the clinical value of MAOA in HCC. Immunohistochemical staining was utilized to determine MAOA protein expression. Intersection genes of MAOA related co‐expressed genes and differentially expressed genes were obtained to perform functional enrichment analyses. In vivo experiment was conducted to study the impact of traditional Chinese medicine nitidine chloride (NC) on MAOA in HCC. Results: MAOA was downregulated and possessed an excellent discriminatory capability in HCC patients. Decreased MAOA correlated with poor prognosis in HCC patients. Downregulated MAOA protein was relevant to an advanced TNM stage in HCC patients. Co‐expressed genes that positively related to MAOA were clustered in chemical carcinogenesis, where CYP2E1 was identified as the hub gene. In vivo experiment showed that nitidine chloride significantly upregulated MAOA in a nude mouse HCC model. Conclusions: A decreased MAOA level is not only correlated with aggressive behaviors in males but also serves as a promising biomarker for the diagnosis and prognosis of HCC patients. Moreover, MAOA may play a role in AFB1 toxic transformation through its synergistic action with co‐expressed genes, especially CYP3A4. MAOA also serves as a potential therapy target of NC in HCC patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression level and potential mechanism of hypoxia‐inducible factor 1 alpha (HIF‐1α) in patients with myelodysplastic syndromes (MDS). Methods: Immunohistochemistry (IHC) techniques were used to examine the protein expression of HIF‐1α in paraffin‐embedded myeloid tissues from 82 patients with MDS and 33 controls (patients with lymphoma that is not invading myeloid tissues). In addition, the associations between the protein expression of HIF‐1α and clinical parameters were examined. To further investigate the significance of HIF‐1α expression in MDS patients, the researchers not only extracted the data about HIF‐1α expression from MDS‐related microarrays but also analyzed the correlation between the level of HIF‐1α expression and MDS. The microRNA (miRNA) targeting HIF‐1α was predicted and verified with a dual luciferase experiment. Results: Immunohistochemistry revealed that the positive expression rate of HIF‐1α in the bone marrow of patients with MDS was 90.24%. This rate was remarkably higher than that of the controls (72.73%) and was statistically significant (P < .05), which indicated that HIF‐1α was upregulated in the myeloid tissues of MDS patients. For the GSE2779, GSE18366, GSE41130, and GSE61853 microarrays, the average expression of HIF‐1α in MDS patients was higher than in the controls. Particularly for the GSE18366 microarray, HIF‐1α expression was considerably higher in MDS patients than in the controls (P < .05). It was predicted that miR‐93‐5p had a site for binding with HIF‐1α, and a dual luciferase experiment confirmed that miR‐93‐5p could bind with HIF‐1α. Conclusion: The upregulated expression of HIF‐1α was examined in the myeloid tissues of MDS patients. The presence of HIF‐1α (+) suggested an unsatisfactory prognosis for patients, which could assist in the diagnosis of MDS. In addition, miR‐93‐5p could bind to HIF‐1α by targeting, showing its potential to be the target of HIF‐1α in MDS. [ABSTRACT FROM AUTHOR]

There is accumulating evidence that miRNA might serve as potential diagnostic and prognostic markers for various types of cancer. Hepatocellular carcinoma (HCC) is the most common type of malignant lesion but the significance of miRNAs in HCC remains largely unknown. The present study aimed to establish the diagnostic value of miR‐101‐3p/5p in HCC and then further investigate the prospective molecular mechanism via a bioinformatic analysis. First, the miR‐101 expression profiles and parallel clinical parameters from 362 HCC patients and 50 adjacent non‐HCC tissue samples were downloaded from The Cancer Genome Atlas (TCGA). Second, we aggregated all miR‐101‐3p/5p expression profiles collected from published literature and the Gene Expression Omnibus and TCGA databases. Subsequently, target genes of miR‐101‐3p and miR‐101‐5p were predicted by using the miRWalk database and then overlapped with the differentially expressed genes of HCC identified by natural language processing. Finally, bioinformatic analyses were conducted with the overlapping genes. The level of miR‐101 was significantly lower in HCC tissues compared with adjacent non‐HCC tissues (P < 0.001), and the area under the curve of the low miR‐101 level for HCC diagnosis was 0.925 (P < 0.001). The pooled summary receiver operator characteristic (SROC) of miR‐101‐3p was 0.86, and the combined SROC curve of miR‐101‐5p was 0.80. Bioinformatic analysis showed that the target genes of both miR‐101‐3p and miR‐101‐5p are involved in several pathways that are associated with HCC. The hub genes for miR‐101‐3p and miR‐101‐5p were also found. Our results suggested that both miR‐101‐3p and miR‐101‐5p might be potential diagnostic markers in HCC, and that they exert their functions via targeting various prospective genes in the same pathways. [ABSTRACT FROM AUTHOR]