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Expression analysis of cancer of unknown primary (CUP)

ABSTRACT: Biopsies (lymph nodes, ascites or hydrothorax) from 60 patients with cancer of unknown primary origin were analyzed. Results provide insight into the molecular pathogenesis of CUP. 60 samples; 1 array per sample

ORGANISM(S): Homo sapiens

SUBMITTER: Yoshihiko Fujita

PROVIDER: E-GEOD-42392 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Expression analysis of cancer of unknown primary (CUP) 2

Project description:Biopsies (lymph nodes, ascites or hydrothorax) from 60 patients with cancer of unknown primary origin were analyzed. Results provide insight into the molecular pathogenesis of CUP.

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Expression analysis of cancer of unknown primary (CUP) 1

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Cancers of unknown primary (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin.

Project description:Employing genome wide transcriptome analysis,Linear Discriminant Analysis (LDA) and Quadratic Discriminant Analysis (QDA), we created a successful classification model to identify the putative origin of a CUP. Using the classifications of the CUPs enable the comparison of transcriptome profiles from CUPs to the equivalent normal metastasis across the different carcinoma types. Gene Set Enrichment Analysis (GSEA) and Pathway analysis were used to reveal the common biological features characterizing CUPs. The classifier was build using 2208 samples of normal tissue, known primary tumors, metastasis of known origin and tested on 60 CUP samples. 130 of these samples were collected and analyzed as part of the project and submitted to ArrayExpress. The analyses show that CUPs are distinct from metastases of known origin. CUPs exhibit inconsistent expression of conventional cancer biomarkers and QDA derived outlier scores show that CUPs are more distantly related to their primary tumor class than corresponding metastases of known origin. Gene set enrichment analysis showed that CUPs display increased expression of genes involved in DNA damage repair and by employing signatures of chromosome instability (CIN), we found that CUPs are chromosome unstable compared to metastases of known origin.

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Expression analysis of cancer of unknown primary (CUP)

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Gene expression profiles in lymph nodes with metastasis of oral squamous cell carcinoma (OSCC)

Project description:Background: Cervical lymph node metastasis is a potent prognostic factor in oral squamous cell carcinoma (OSCC). However, lymph nodes resected by sentinel node biopsy or neck dissection are usually diagnosed by examining only one or two sections of the maximal cut surface. Accurate diagnosis of the metastasis in lymph nodes is important but depends on a heavy workload of the pathologist. In this study, we have attempted to identify novel molecular markers to find the harboring cancer cells in the lymph node and establish rapid detection method. Methods: We determined the gene expression profiles of 7 metastatic lymph nodes from patients with OSCC and 1 normal lymph node and 5 salivary glands from non-cancerous patients by microarray analysis. We found the overexpression genes in all metastatic lymph nodes. Subsequently, we examined the expression of these genes in newly 23 metastatic lymph nodes and 9 normal lymph nodes by real-time quantitative RT-PCR (qRT-PCR) assay. Moreover, the rapid detection of lymph node metastasis by these genes was examined using the reverse transcription loop-mediated isothermal amplification (RT-LAMP) method. Result: Among the 4 genes identified by microarray analysis, annexin A8 (ANXA8) and desmoglein 3 (DSG3) were detected in all metastatic lymph nodes at a much higher level but not in normal lymph nodes at all by qRT-PCR. Furthermore, RT-LAMP method targeting ANXA8 rapidly detected almost lymph nodes with metastasis. Conclusions: ANXA8 could be a useful marker for detecting lymph node metastasis in OSCC. Using AB1700 system, we determined the gene expression profiles of lymph nodes with metastasis of OSCC. Normal lymph node and salivary gland tissues were used as control samples.

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DNA methylation profiles of lymph node tissue of head and neck cancer of unknown primary

Project description:Background. The unknown tissue of origin in head and neck cancer of unknown primary (hnCUP) leads to invasive diagnostic procedures and unspecific and potentially inefficient treatment options for patients. The most common histological subtype, squamous cell carcinoma, can stem from various tumor primary sites, including the oral cavity, oropharynx, larynx, head and neck skin, lungs, and esophagus. DNA methylation profiles are highly tissue-specific and have been successfully used to classify tissue origin. We therefore developed a support vector machine (SVM) classifier trained with publicly available DNA methylation profiles of commonly cervically metastasizing squamous cell carcinomas (n = 1,103) in order to identify the primary tissue of origin of our own cohort of squamous cell hnCUP patient’s samples (n = 28). Methylation analysis was performed with Infinium MethylationEPIC v1.0 BeadChip by Illumina. Results. The SVM algorithm achieved the highest overall accuracy of tested classifiers, with 87%. Squamous cell hnCUP samples on DNA methylation level resembled squamous cell carcinomas commonly metastasizing into cervical lymph nodes. The most frequently predicted cancer localization was the oral cavity in 11 cases (39%), followed by the oropharynx and larynx (both 7, 25%), skin (2, 7%), and esophagus (1, 4%). These frequencies concord with the expected distribution of lymph node metastases in epidemiological studies. Conclusions. On DNA methylation level, hnCUP is comparable to primary tumor tissue cancer types that commonly metastasize to cervical lymph nodes. Our SVM-based classifier can accurately predict these cancers’ tissues of origin and could significantly reduce the invasiveness of hnCUP diagnostics and enable a more precise therapy after clinical validation.

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