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ZNF-281 as the Potential Diagnostic Marker of Oral Squamous Cell Carcinoma.

ABSTRACT: ZNF-281 is a zinc finger factor which can lead to cancer progression and metastasis. Its up-regulation reported in many cancers was correlated with metastasis and worsened patients' prognosis. This is the first study describing ZNF-281 in the context of OSCC. Oral tissue samples drawn from 66 OSCC patients and 36 control patients were collected to determine protein (using immunochemistry and the semi-quantitative H-score method) and mRNA expression levels (using the RT-qPCR reaction). Our aim was to assess the ZNF-281 expression level in OSCC and the control group. Moreover, we determined the impact of ZNF-281 on survival parameters and the association of diversified clinical parameters with ZNF-281 expression. Clinical factors such as grade, AJCC stage and radiotherapy have an impact on the ZNF-281 H-score level, whereas AJCC stage and grade have an influence on ZNF-281 mRNA expression. Our survival analysis indicated that the impact on overall survival is not statistically significant, and the prognostic potential of ZNF-281 is rather limited. Our findings show that both levels of the ZNF-281 H-score and mRNA are decreased in OSCC in comparison to normal tissue. Moreover, we estimated that the H-score can differentiate normal tissue from OSCC with a sensitivity of 97% and specificity of 93.7%.

SUBMITTER: Starzynska A

PROVIDER: S-EPMC8197962 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: The differential abundance of cell-free RNAs in bodily fluids is emerging as a promising tool for the non-invasive molecular diagnosis of cancer. Human saliva is considered a promising source of non-invasive biomarkers of diagnostic value for oral cancer detection. This study aims to identify diagnostic potent salivary RNAs in oral squamous cell carcinoma (OSCC)-patients by RNA-Sequencing. Method: Unstimulated saliva was collected from 5 normal control (NC) individuals and 9 OSCC patients (PS) with prior consent and ethical committee approvals. Total RNA isolated from cell-free saliva (CFS) supernatant was used to prepare small RNA libraries and sequenced on the Ion Torrent S5 platform. The sequencing reads were aligned to the human genome (hg19) using Bowtie 2, and the differential expression analysis was performed using RUVSeq and DESeq2. Mapped reads were screened across miRBase (v22) annotations for miRNAs and Gencode (v19) annotation for other RNAs. Reads were quantified by the Featurecount (v1.4.6) module of the R-package. The microbial-RNA enrichment analysis was determined using the One Codex platform. Result: RNA-sequencing detected protein-coding transcripts (PCTs), long-intergenic RNAs (lincRNAs), microRNAs (miRNAs), small nuclear RNAs (snRNAs), transfer RNAs (tRNAs) and pseudogenes from the saliva of PS and HC samples. Transcriptome analyses revealed 89 PCTs, 18 lincRNAs and 6 miRNAs differentially expressed between PS and HC with a log2fold change ≥ 1 or ≤ -1 and p-value < 0.05. Gene ontology and pathway enrichment analyses indicated a significant correlation of the identified PCTs and miRNAs to various cancer-related pathways that may have implications in the pathogenesis of OSCC. Interestingly, unmapped non-human reads aligned to the microbial reference genomes. Further analyses of these microbial sequence reads revealed a significant microbial dysbiosis differentiating PS from HC. Metabolic pathways and functional analysis of the identified microbial phylotypes showed gene ontologies associated with inflammation, cell proliferation, ROS generation, and a range of metabolic processes. Conclusion: We report novel panels of differentially expressed PCTs, miRNAs and lincRNAs distinguishing PS from HC. Importantly, our results also provide evidence for oral microbial dysbiosis that appears to have pathological implications in OSCC. Summarily, this study provides a comprehensive landscape of salivary RNAs that can be exploited as non-invasive biomarkers for OSCC detection.

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ZNF-281 as the Potential Diagnostic Marker of Oral Squamous Cell Carcinoma.

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