Spatial Multi-omics Reveals the Heterogeneity of Tumor Microenvironment in the OSF-Associated OSCC
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ABSTRACT:
PROVIDER: PRJNA912193 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22739265_1.fastq.gz | Fastqsanger.gz | |||
| SRR22739265_2.fastq.gz | Fastqsanger.gz | |||
| SRR22739266_1.fastq.gz | Fastqsanger.gz | |||
| SRR22739266_2.fastq.gz | Fastqsanger.gz | |||
| SRR22739267_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: Oral squamous cell carcinoma (OSCC) is a major world health problem with over 400,000 new cases diagnosed annually. Despite advances in surgery and chemo-radiotherapy, the 5 year survival has remained roughly constant at approximately 50% for several decades. The disease is characterized by both clinical and genetic heterogeneity, so elucidating the molecular basis of this heterogeneity would have significant clinical implications. It is well recognized that OSCCs from Asia that are associated with betel quid chewing are phenotypically distinct from those from the West that are predominantly caused by smoking/drinking, but the genetic basis of these differences are largely unknown. The aim of this study is to examine the most related genetic factors, carcinogenic related pathways, and molecular processes that might be responsible for the phenotypic heterogeneity of OSCC between UK and Sri Lankan population groups. Methods: We have compared the gene expression profiles of OSCCs and normal oral mucosal tissues from both Sri Lankan and UK individuals using Affymetrix gene expression arrays. Results: The gene expression profiles of UK and Sri Lankan OSCC are similar in many respects to other oral cancer expression profiles reported in the literature and were mainly similar to each other. However, genes involved in tumor invasion, metastasis and recurrence were more obviously associated with UK tumors as opposed to those from Sri Lanka. Interestingly, Ingenuity Pathway Analysis (IPA) revealed a highly activated cell-mediated immune response in both Sri Lankan normal and tumor samples relative to UK cohorts, which may, in part, explain the less aggressive behavior of these betel quid-induced OSCCs. Conclusion: The development of OSCCs in both UK and Sri Lankan populations appears largely mediated by similar biological pathways despite the differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. However, IPA revealed a highly activated M-bM-^@M-^\Cell-mediated Immune ResponseM-bM-^@M-^] in Sri Lankan normal and tumor samples relative to UK cohorts. It seems likely, therefore, that any future attempts to personalize treatment for OSCC patients will need to be different in Western and Asian countries to reflect differences in gene expression and the immune status of the patients. All biopsy specimens of OSCC and normal oral mucosa were harvested with appropriate ethical approval and informed consent of individual patients (LREC 0769). Identical protocols for tissue collection and processing were used in both countries. OSCC samples were obtained from sequential incident cases treated by a single consultant surgeon from 2001 to 2004 at University Hospital of Birmingham, NHS Foundation Trust, Birmingham, UK, and Kandy General Hospital, Kandy, Sri Lanka. A total of 21 UK and 27 Sri Lankan samples yielded RNA of sufficient quality and quantity for microarray analysis. In addition, 8 normal oral mucosa specimens (five samples from UK & three samples from Sri Lankan population) were also profiled. All normal samples were from non-smokers, who did not chew betel quid and did not consume in excess of the national recommended weekly gender allowance of alcohol. Normal samples were taken from individuals with no history of cancer and had no first degree relatives with a history of cancer.
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Project description:Hypoxic microenvironment plays important roles in the progression of solid tumors including oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) have gained much attention in the past few years. However, it is not clear whether lncRNAs could regulate hypoxia-adaptation of OSCC, and which lncRNAs participate in this process. Using an lncRNA microarray, we analyzed the aberrant lncRNA expression profiles in OSCC tissues compared with paired normal oral mucosa as well as in hypoxic OSCC cells compared with normoxic OSCC cells. Our data revealed 2053 differentially expressed (Fold Change >= 2.0, P-value <= 0.05) lncRNAs, among which 934 lncRNAs were significantly up-regulated and 1119 lncRNAs were down-regulated in OSCC compared with paired normal mucosa. Six OSCC tissues and paired normal oral mucosa were obtained from 6 patients with OSCC. LncRNA expression profiles were evaluated by an Agilent Human LncRNA Array v3.0 (8 x 60K, Arraystar).
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Project description:Hypoxic microenvironment plays important roles in the progression of solid tumors including oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) have gained much attention in the past few years. However, it is not clear whether lncRNAs could regulate hypoxia-adaptation of OSCC, and which lncRNAs participate in this process. Using an lncRNA microarray, we analyzed the aberrant lncRNA expression profiles in OSCC tissues compared with paired normal oral mucosa as well as in hypoxic OSCC cells compared with normoxic OSCC cells. Our microarray also identified 942 lncRNAs that were up-regulated and 507 lncRNAs that were down-regulated in cells cultured under hypoxia compared with those cultured under normoxia (Fold Change >= 2.0, P-value <= 0.05). An OSCC cell line Cal-27 was cultured under either 20% O2 (normoxic) or 1% O2 (hypoxic) conditions. Three samples from each group were obtained for microarray study.
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