scholarly journals Histologically resolved spatial multi-omics of human oral squamous cell carcinoma

2017 ◽  
Author(s):  
Tao Chen ◽  
Chen Cao ◽  
Jianyun Zhang ◽  
Aaron Streets ◽  
Yanyi Huang ◽  
...  

AbstractBoth the composition of cell types and their spatial distribution in a tissue play a critical role in cellular function, organ development, and disease progression. For example, intratumor heterogeneity and the distribution of transcriptional and genetic events in single cells drive the genesis and development of cancer. However, it can be challenging to fully characterize the molecular profile of cells in a tissue with high spatial resolution because microscopy has limited ability to extract comprehensive genomic information, and the spatial resolution of genomic techniques tends to be limited by dissection. There is a growing need for tools that can be used to explore the relationship between histological features, gene expression patterns, and spatially correlated genomic alterations in healthy and diseased tissue samples. Here, we present a technique that combines label-free histology with spatially resolved multi-omics in un-fixed and unstained tissue sections. This approach leverages stimulated Raman scattering microscopy to provide chemical contrast that reveals histological tissue architecture, allowing for high-resolution in situ laser micro-dissection of regions of interests. These micro-tissue samples are then processed for DNA and RNA sequencing to identify unique genetic profiles that correspond to distinct anatomical regions. We demonstrate the capabilities of this technique by mapping gene expression and copy number alterations to histologically defined regions in human squamous cell carcinoma (OSCC). Our approach provides complementary insights in tumorigenesis and offers an integrative tool for macroscale cancer tissues with spatial multi-omics assessments.

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhenyuan Han ◽  
Biao Yang ◽  
Yu Wang ◽  
Xiuxia Zeng ◽  
Zhen Tian

5-Methylcytosine (m5C) methylation is a major epigenetic technique of RNA modification and is dynamically mediated by m5C “writers,” “erasers,” and “readers.” m5C RNA modification and its regulators are implicated in the onset and development of many tumors, but their roles in head and neck squamous cell carcinoma (HNSCC) have not yet been completely elucidated. In this study, we examined expression patterns of core m5C regulators in the publicly available HNSCC cohort via bioinformatic methods. The differentially expressed m5C regulators could divide the HNSCC cohort into four subgroups with distinct prognostic characteristics. Furthermore, a three-gene expression signature model, comprised of NSUN5, DNMT1, and DNMT3A, was established to identify individuals with a high or low risk of HNSCC. To explore the underlying mechanism in the prognosis of HNSCC, screening of differentially expressed genes, followed by the analysis of functional and pathway enrichment, from individuals with high- or low-risk HNSCC was performed. The results revealed a critical role for m5C RNA modification in two aspects of HNSCC: (1) dynamic m5C modification contributes to the regulation of HNSCC progression and (2) expression patterns of NSUN5, DNMT1, and DNMT3A help to predict the prognosis of HNSCC.


Author(s):  
Naghmeh Emami ◽  
Naghmeh Bahrami ◽  
Masoumeh Mirzaei ◽  
Abdolreza Mohamadnia

Introduction: Oral Squamous Cell Carcinoma (OSCC) is one of the most common oral malignancies, which accounts for 80-90% of malignant neoplasms of the oral cavity. MicroRNAs (miRNAs) are small RNA molecules that regulate post-transcriptional gene expression by targeting mRNAs. Materials and Methods: In this case-control study, 40 patients with oral squamous cell carcinoma and 40 healthy individuals as control were studied. Blood samples were collected from both groups. Also, 30 cancer tissue samples and 30 healthy tissue samples were prepared and evaluated. RNA was extracted from collected peripheral blood and tissue samples and evaluated for the expression level of miR-494 via real-time PCR technique. P. value values<0.05 were considered statistically significant. Results: The expression level of miR-494 in serum (peripheral blood) of patients with oral squa- mous cell carcinoma increased by 1.12 fold (P-value<0.001) compared with healthy individuals. Also, the expression level of miR-494 in samples of oral squamous cell carcinoma infected tissue showed a 1.28-fold increase compared to healthy tissue. Conclusion: The results of this study indicate an increase in the expression level (up-regula- tion) of miR-494 in oral squamous cell carcinoma. This biomarker can be used in screening and early detection of oral squamous cell carcinoma.


Oncotarget ◽  
2015 ◽  
Vol 6 (25) ◽  
pp. 20902-20920 ◽  
Author(s):  
Joao Paulo Oliveira-Costa ◽  
Alex Fiorini de Carvalho ◽  
Giorgia Gobbi da Silveira ◽  
Peter Amaya ◽  
Yongqi Wu ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Markéta Čapková ◽  
Jana Šáchová ◽  
Hynek Strnad ◽  
Michal Kolář ◽  
Miluše Hroudová ◽  
...  

With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey’sPvalue<0.05) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 42-42
Author(s):  
Seiya Inoue ◽  
Takeshi Nishino ◽  
Masakazu Goto ◽  
Daisuke Yoshida ◽  
Akira Tangoku

Abstract Background Neo-adjuvant chemotherapy (NAC) became to be a standard therapeutic strategy for advanced esophageal squamous cell carcinoma in Japan. However the multidrug combination chemotherapy with 5-FU, cisplatin (FP) and docetaxel (DFP) has been well known more effective than FP, biomarker predict efficacy of NAC is not known yet. We have reported that expression of HER2 and EGFR had correlated to the response of neoadjuvant chemotherapy and prognosis. Therefore we started to evaluate them in all cases using biopsy tissue samples from 2012. Methods The tissues were collected from 122 patients with esophageal squamous cell carcinoma before NAC with DFP from August 2012 to August 2017, and expression of HER2 and EGFR were measured with Immunohistochemistry. HER2 positive were 2 + and 3 + expression in immunostaining. The number of the patients were 20 cases in stageII, 91 cases in stageIII, and 11 cases in stageIV. These results were compared with response to NAC and outcome of the patients. Results There were no differences in patient background factors such as sex, age, location and stage.One hundred nineteen of 122 cases (97.5%) were positive for EGFR and HER2 positive cases were 12 cases (9.8%). Expression patterns of EGFR and HER2 were examined, EGFR positive-HER2 negative cases were the most common pattern, and 107 cases (87.7%), both positive were 12 cases (9.8%), and both negative were 3 cases (2.4%), EGFR negative-HER2 positive were not observed. The response rates of chemotherapy was 46.2% in the EGFR positive cases, it was 42.9% in EGFR positive-HER2 negative cases. It was 75% in HER2 and EGFR positive cases, and it was significantly higher than the other pattern (P = 0.034). HER2 expression was suggested to be a biomarker of NAC with DFP especially in stage III. Conclusion HER2 and EGFR expression was shown to be a predictor of NAC response. The patients with both negative pattern showed poorer response. The expression pattern of HER2 and EGFR can be useful biomarker of NAC response with DFP. Disclosure All authors have declared no conflicts of interest.


2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Joao Paulo Oliveira‐Costa ◽  
Alex Fiorini Carvalho ◽  
Giorgia Gobbi Silveira ◽  
Dirce Maria Carraro ◽  
Fernando Augusto Soares ◽  
...  

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