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Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome.

ABSTRACT: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40-50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral microbiome studies putatively identifying relevant bacterial species. As the impact of other microbial organisms, such as fungi and viruses, has largely been neglected, a bioinformatic approach utilizing the Trans-Proteomic Pipeline (TPP) and the R statistical programming language was implemented here to investigate not only bacteria, but also viruses and fungi in the context of a publicly available, OSCC, mass spectrometry (MS) dataset. Overall viral, bacterial, and fungal composition was inferred in control and OSCC patient tissue from protein data, with a range of proteins observed to be differentially enriched between healthy and OSCC conditions, of which the fungal protein profile presented as the best potential discriminator of OSCC within the analysed dataset. While the current project sheds new light on the fungal and viral spheres of the oral microbiome in cancer in silico, further research will be required to validate these findings in an experimental setting.

SUBMITTER: He S

PROVIDER: S-EPMC9865486 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome.

He Steven S Chakraborty Rajdeep R Ranganathan Shoba S

International journal of molecular sciences 20230105 2

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40-50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral microbiome studies putatively identifying relevant bacterial species. As the impact of other microbial organisms, such as fungi and viruses, has largely been neglected, a bioinformatic approach utilizing the Trans-Proteomic Pipel ...[more]

PMID: 36674563

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Project description:IntroductionCircular RNAs (CircRNAs), an emerging non-coding RNA, have been demonstrated to be involved in tumorigenesis, metastasis, and cancer progression, and could represent novel potential biomarkers for diagnosing oral squamous cell carcinoma (OSCC). However, no meta-analysis has investigated the diagnostic role of circRNAs in OSCC. Hence, to investigate whether circRNAs could serve as specific biomarkers for OSCC, the present systematic review and meta-analysis evaluated the diagnostic efficiency of circRNAs in patients with OSCC.Materials and methodsA thorough search of online databases (Pubmed, Web of Science, Embase, and the Cochrane Library) was conducted to collect relevant studies up to March 30th, 2021. All eligible studies were case-control studies. The quality of each study was evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. STATA (version 15.1) and Review Manager (version 5.4) were employed to conduct the meta-analysis, and the PRISMA statement was adopted in this study.ResultsA total of 16 studies were included in the meta-analysis, with five studies on upregulated circRNAs, and 11 on downregulated circRNAs. The enrolled studies that met our eligibility criteria all derived from China. The pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the area under receiver operating characteristics curve (AUC) with the 95% confidence intervals (95% CIs) were 0.74 (0.69-0.79), 0.79 (0.73-0.84), 10.74 (7.81-14.77), 3.50 (2.78-4.45), 0.33 (0.27-0.39) and 0.83 (0.79-0.86), respectively. The subgroup analysis demonstrated that serum, plasma, and saliva specimens had a better diagnostic performance than tissue samples, with a high value of sensitivity, specificity, DOR, and AUC values. The results also showed that the subgroups of upregulated circRNAs and a sample size of ≥100 manifested higher specificity, DOR, and AUC for cancer detection than downregulated circRNAs and a sample size of < 100.ConclusionsA strong association was demonstrated between the dysregulated expression of circRNAs and the diagnosis of OSCC. Hence, circRNAs have the potential to function as promising biomarkers and therapeutic targets for OSCC.Systematic review registrationPROSPERO, number CRD42021256857.

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.

Project description:BackgroundNeuropilin-2 (NRP2) is a single chain transmembrane glycoprotein that acts as a co-receptor of VEGF and is related to the pathogenesis of various tumors closely. However, the clinical significance of NRP2 in oral squamous cell carcinoma (OSCC) is unclear.PurposeThe objective of this study was to investigate the role of NRP2 in the pathogenesis of OSCC and explore the associated mechanisms.Materials and methodsGEPIA (gene expression profiling interactive analysis) was used to analyze the expression of NRP2 in OSCC. Immunohistochemistry and RT-qPCR were used to detect NRP2 expression in 80 OSCC samples. The clinical correlations and prognostic significance of NRP2 expression were evaluated. In addition, the biological functions of OSCC cells transfected with shNRP2 were evaluated. The expression levels of β-catenin, C-myc, cyclin D1, and MMP-2 in Wnt/β-catenin signaling pathway were assessed by RT-qPCR after inhibiting the expression of NRP2 in SCC-25 cell line.ResultsAnalysis of cases using GEPIA revealed that NRP2 was substantially upregulated in OSCC. NRP2 expression was also significantly higher in our OSCC samples than in the controls. Elevated expression of NRP2 was correlated with lymph node metastasis (P<0.01) and distant metastasis (P<0.05) in OSCC patients, and high NRP2 levels, lymph node metastasis, and distant metastasis were associated with poor prognosis (Kaplan-Meier analysis; P<0.05). Univariate and multivariate Cox analysis showed that lymph node metastasis, distant metastasis, and NRP2 expression were independent risk factors for overall survival (OS) and disease-free survival (DFS) in OSCC patients (P<0.05). Furthermore, the proliferation, migration, and invasion of OSCC cells were inhibited by shNRP2. Following inhibiting of NRP2 expression in the SCC-25 cell line, the expression levels of β-catenin, C-myc, cyclin D1, and MMP-2 were reduced (P<0.05).ConclusionThis study shows that NRP2 functions as a tumor promoter gene in OSCC by affecting the proliferation, migration, and invasion of OSCC cells and downregulating the Wnt/β-catenin pathway. These results highlight the potential role for NRP2 as a clinical diagnostic marker.

Dataset Information

Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome.

Publications

Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome.

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