Non-coding RNA and hepatitis B virus-related hepatocellular carcinoma: A bibliometric analysis and systematic review.

Objectives: A bibliometric analysis for non-coding RNA and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) was performed to describe international research status and visualize the research scope and emerging trends over the last two decades on this topic. Materials and methods: Research data of non-coding RNA and HBV-related HCC were retrieved and extracted from the Web of Science Core Collection (WoSCC) database from 1 January 2003 to 13 June 2022 and then analyzed by means of bibliometric methods. A total of 1,036 articles published in this field were assessed for specific characteristics, including the year of publication, journal, author, institution, country/region, references, and keywords. VOSviewer was employed to perform co-authorship, co-occurrence, and co-citation analyses accompanied by constructing a visual network. Results: Overall, 1,036 reports on non-coding RNA and HBV-related HCC from 2003 to 2022 were retrieved from WoSCC. The publication has gradually increased during the last two decades with 324 journals involved. Most research records (748 publications and 23,184 citations) were concentrated in China. A co-occurrence cluster analysis for the top 100 keywords was performed and four clusters were generated: (1) non-coding RNA as a molecular marker for the diagnosis and prognosis of HBV-related HCC; (2) dysregulation of non-coding RNA by hepatitis B virus X protein (HBx); (3) non-coding RNA affecting the biological behaviors of HBV-related HCC; and (4) epidemiological study for the effects of non-coding RNA on the risk of HBV-related HCC. Conclusion: The publications and citations involved in non-coding RNA and HBV-related HCC have increased over the last two decades associated with many countries, institutions, and authors. Our study revealed current development trends, global cooperation models, basic knowledge, research hotspots, and emerging frontiers in this field.

The role of non-coding RNA in the diagnosis and treatment of Helicobacter pylori-related gastric cancer, with a focus on inflammation and immune response.

Helicobacter pylori (H. pylori) is one of the globally recognized causative factors of gastric cancer (GC). Currently, no definite therapy and drugs for H. pylori-related GC have been widely acknowledged although H. pylori infection could be eradicated in early stage. Inflammation and immune response are spontaneous essential stages during H. pylori infection. H pylori may mediate immune escape by affecting inflammation and immune response, leading to gastric carcinogenesis. As an important component of transcriptome, non-coding RNAs (ncRNAs) have been proven to play crucial roles in the genesis and development of H. pylori-induced GC. This review briefly described the effects of ncRNAs on H. pylori-related GC from the perspective of inflammation and immune response, as well as their association with inflammatory reaction and immune microenvironment. We aim to explore the potential of ncRNAs as markers for the early diagnosis, prognosis, and treatment of H. pylori-related GC. The ncRNAs involved in H. pylori-related GC may all hold promise as novel therapeutic targets for immunotherapy.

RNA-sequencing reveals the expression profiles of tsRNAs and their potential carcinogenic role in cholangiocarcinoma.

BACKGROUND: Recently, the incidence of cholangiocarcinoma (CCA) has gradually increased. As CCA has a poor prognosis, the ideal survival rate is scarce for patients. The abnormal expressed tsRNAs may regulate the progression of a variety of tumors, and tsRNAs is expected to become a new diagnostic biomarker of cancer. However, the expression of tsRNAs is obscure and should be elucidated in CCA. METHODS: High-throughput RNA sequencing technology (RNA-seq) was utilized to determine the overall expression profiles of tsRNAs in three pairs CCA and adjacent normal tissues and to screen the tsRNAs that were differentially expressed. The target genes of dysregulated tsRNAs were predicted and the biological effects and potential signaling pathways of these target genes were explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate 11 differentially expressed tRFs with 12 pairs CCA and adjacent normal tissues. RESULTS: High-throughput RNA-seq totally demonstrated 535 dysregulated tsRNAs, of which 241 tsRNAs were upregulated, such as tRF-21-YLKZKWE5D，tRF-16-9NF5W8B，tRF-27-78YLKZKWE52，tRF-19-RLXN48KP，tRF-33-IK9NJ4S2I7L7DV，tRF-19-F8DHXYIV, and 294 tsRNAs were downregulated (tRF-20-739P8WQ0, tRF-34-JJ6RRNLIK898HR, tRF-17-VL8RPY5, tRF-23-YP9LON4VDP, tRF-39-EH623K76IR3DR2I2, tRF-17-18YKISM, tRF-19-Q1Q89PJZ, etc.) in CCA compared with adjacent normal tissues (|log2 [fold change] | ≥ 1 and p value <0.05). GO and KEGG enrichment analyses indicated that the target genes of dysregulated tRFs (tRF-34-JJ6RRNLIK898HR, tRF-38-0668K87SERM492V, and tRF-39-0668K87SERM492E2) were mainly enriched in the Notch signaling pathway, Hippo signaling pathway, cAMP signaling pathway and in growth hormone synthesis, secretion and action, etc. qRT-PCR result showed that tRF-34-JJ6RRNLIK898HR/tRF-38-0668K87SERM492V/tRF-39-0668K87SERM492E2 was downregulated (p = 0.021), and tRF-20-LE2WMK81 was upregulated in CCA (p = 0.033). CONCLUSION: Differentially expressed tRFs in CCA are enriched in many pathways associated with neoplasms, which may impact the tumor progression and have potential to be diagnostic biomarkers and therapeutic targets of CCA.

Predicting Prognosis of Hepatocellular Carcinoma Patients Based on the Expression Signatures of Mitophagy Genes.

Background: The unbalance of mitophagy was closely related to hepatocellular carcinoma (HCC) progression. At present, it has not been uncovered about the influence of mitophagy genes on HCC prognosis and their potential pathogenesis. Materials and Methods: The expression and clinical information of HCC in TCGA cohort were used to identify mitophagy differentially expressed genes (MDEGs) with prognostic value. The prognostic model of mitophagy genes was built and externally validated by LASSO regression in TCGA cohort and ICGC cohort, respectively. The function of the prognostic signature and its association with immune cell infiltration were explored. The profile of MDEGs was validated with 39 pairs HCC and paracarcinoma tissues by quantitative reverse transcription-PCR (qRT-PCR). Results: A total of 18 mitophagy genes that were upregulated and contributed to poor prognosis in HCC were identified. These genes could interact with each other. The correlation analysis showed that there was positively correlation among mitophagy genes. According to optimal λ value, 8 mitophagy gene signatures were involved in prognostic model. Based on median risk scores, HCC patients were divided into high-risk group and low-risk group. Compared with the low-risk group, the high-risk group has worse overall survival in TCGA cohort and ICGC cohort. The univariate and multivariate Cox regression analysis suggested that risk score was an independent prognostic factor of HCC patients. Time-dependent ROC curve was used to identify and validate good predicting performance of the prognostic model. Enrichment analysis showed that risk differentially expressed genes were enriched in various metabolism and cell division processes. The immune cell infiltration score and immune function were significantly different in two groups. qRT-PCR validation result showed that QSTM1, CSNK2B, PGAM5, and ATG5 were upregulated. Conclusion: Mitophagy genes could influence HCC progression through regulating the metabolism and immune functions and could be used to predict prognosis and considered as potential prognostic biomarker and precise therapeutic target of HCC.

Comprehensive assessment for miRNA polymorphisms in hepatocellular cancer risk: a systematic review and meta-analysis.

MiRNA polymorphisms had potential to be biomarkers for hepatocellular cancer (HCC) susceptibility. Recently, miRNA single nucleotide polymorphisms (SNPs) were reported to be associated with HCC risk, but the results were inconsistent. We performed a systematic review with a meta-analysis for the association of miRNA SNPs with HCC risk. Thirty-seven studies were included with a total of 11821 HCC patients and 15359 controls in this meta-analysis. We found hsa-mir-146a rs2910164 was associated with a decreased HCC risk in the recessive model (P=0.017, OR = 0.90, 95% confidence interval (CI) = 0.83-0.98). While hsa-mir-34b/c rs4938723 was related with an increased HCC risk in the co-dominant model (P=0.016, odds ratio (OR) = 1.19, 95%CI = 1.03-1.37). When analyzing the Hepatitis B virus (HBV)-related HCC risk, hsa-mir-196a-2 rs11614913 was associated with a decreased HBV-related HCC risk in the co-dominant and allelic models. And hsa-mir-149 rs2292832 was found to be associated with a decreased HBV-related HCC risk in the dominant and recessive models. In conclusion, hsa-mir-146a rs2910164 and hsa-mir-34b/c rs4938723 could be biomarkers for the HCC risk while hsa-mir-196a-2 rs11614913 and hsa-mir-149 rs2292832 had potential to be biomarkers for HBV-related HCC risk.

A comprehensive evaluation for polymorphisms in let-7 family in cancer risk and prognosis: a system review and meta-analysis.

miRNA polymorphisms had potential to be biomarkers for cancer susceptibility and prognosis. The mature miRNA-let-7 family was considered as the most important miRNA for the cancer incidence and progression. Recently, the promising let-7 miRNAs were reported to be associated with various cancers, but the results were inconsistent. We performed a first-reported systematic review with a meta-analysis for the association of let-7 family single nucleotide polymorphisms (SNPs) with cancer risk/prognosis. Ten studies were included with a total of 3878 cancer cases and 4725 controls for the risk study and 1665 cancer patients for the prognosis study in this meta-analysis. In the risk study, the let-7i rs10877887 and let-7a-1/let-7f-1/let-7d rs13293512 were shown no significant association for the overall cancer risk. In the stratified analysis, the rs10877887 variant genotype was significantly associated with a decreased cancer risk in head and neck cancer (TC compared with TT: P=0.017; odds ratio (OR) = 0.81; TC + CC compared with TT: P=0.020; OR = 0.82). In the prognosis study, the let-7i rs10877887 SNP was shown to be associated with a higher risk for cancer prognosis in the dominate model (P=0.004; hazard ratio (HR) = 1.32). The other two SNPs (let-7a-1 rs10739971 and let-7a-2 rs629367) were not found to be associated with cancer survival. None of the let-7 family polymorphisms had potential to be biomarkers for cancer susceptibility but let-7i rs10877887 SNP had potential to be predicting markers for cancer prognosis. In the future, large-sample studies are still needed to verify our findings.