Gene expression profiling of tumor-adjacent histologically normal lung tissues from lung SCC patients
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ABSTRACT: Tumor-adjacent noncancerous tissues often exhibited abnormalities on molecular levels, which is described as field effect of cancerization. Accumulated evidence demonstrated that filed effect may also play important role in cancer progression. In the present study, we found that the gene expression profile in noncancerous lung tissues adjacent to lung squamous cell carcinoma (SCC) was significantly associated with regional lymph node status of patients. Significance Analysis of Microarrays (SAM) showed that 121 genes were significantly associated with lymph node metastasis (delta=0.75, FDR=0.069). Interestingly, all of the significant genes were up-regulated in the lymph node positive samples. For these genes, the most significant biological GO terms were extracellular structure organization, cell adhesion, regulation of cell motion/migration, and vessel development, etc, which were also involved in EMT process supported by another experiment in vitro. Tumor-adjacent histologically normal lung tissues were collected from 60 primary lung SCC patients, of whom 34 (56.7%) suffered regional lymph node metastasis. Gene expression profiling analysis of these samples was performed using Agilent 4x44K human whole genome gene expression microarray (G4112F).
Project description:Tumor-adjacent noncancerous tissues often exhibited abnormalities on molecular levels, which is described as field effect of cancerization. Accumulated evidence demonstrated that filed effect may also play important role in cancer progression. In the present study, we found that the gene expression profile in noncancerous lung tissues adjacent to lung squamous cell carcinoma (SCC) was significantly associated with regional lymph node status of patients. Significance Analysis of Microarrays (SAM) showed that 121 genes were significantly associated with lymph node metastasis (delta=0.75, FDR=0.069). Interestingly, all of the significant genes were up-regulated in the lymph node positive samples. For these genes, the most significant biological GO terms were extracellular structure organization, cell adhesion, regulation of cell motion/migration, and vessel development, etc, which were also involved in EMT process supported by another experiment in vitro.
Project description:Objective: The purpose of this study was to investigate the molecular basis of tumorigenesis and regional lymph node metastasis in LSCC, and provide a set of genes that may be useful for the development of novel diagnostic markers and/or more effective therapeutic strategies. Methods: A total number of 10 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for microarray analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by Illumina mRNA microarrays,and LSCC tissues with regional lymph node metastasis and LSCC tissues without regional lymph node metastasis were analyzed in the same manner.The most frequently differently expressed genes screened by microarrays were also validated by qRT-PCR in another 42 patients diagnosed for LSCC . Results: Analysed by Illumina mRNA microarrays,there were 361 genes significantly related to tumorigenesis while 246 genes significantly related to regional lymph node metastasis in LSCC. We found that the six genes (CDK1,CDK2,CDK4,MCM2,MCM3,MCM4) were most frequently differently expressed functional genes related to tumorigenesis while eIF3a and RPN2 were most frequently differently expressed functional genes related to regional lymph node metastasis in LSCC. The expressions of these genes were also validated by qRT-PCR. Conclusions: The research revealed a gene expression signature of tumorigenesis and regional lymph node metastasis in laryngeal squamous cell carcinoma.Of the total, the deregulation of several genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4, EIF3a and RPN2) were potentially associated with disease development and progression. The result will contribute to the understanding of the molecular basis of LSCC and help to improve diagnosis and treatment. A total number of 10 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for microarray analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by Illumina mRNA microarrays,and LSCC tissues with regional lymph node metastasis and LSCC tissues without regional lymph node metastasis were analyzed in the same manner.The most frequently differently expressed genes screened by microarrays were also validated by qRT-PCR in another 42 patients diagnosed for LSCC .
Project description:Objective: The purpose of this study was to investigate the molecular basis of tumorigenesis and regional lymph node metastasis in LSCC, and provide a set of genes that may be useful for the development of novel diagnostic markers and/or more effective therapeutic strategies. Methods: A total number of 10 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for microarray analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by Illumina mRNA microarrays,and LSCC tissues with regional lymph node metastasis and LSCC tissues without regional lymph node metastasis were analyzed in the same manner.The most frequently differently expressed genes screened by microarrays were also validated by qRT-PCR in another 42 patients diagnosed for LSCC . Results: Analysed by Illumina mRNA microarrays,there were 361 genes significantly related to tumorigenesis while 246 genes significantly related to regional lymph node metastasis in LSCC. We found that the six genes (CDK1,CDK2,CDK4,MCM2,MCM3,MCM4) were most frequently differently expressed functional genes related to tumorigenesis while eIF3a and RPN2 were most frequently differently expressed functional genes related to regional lymph node metastasis in LSCC. The expressions of these genes were also validated by qRT-PCR. Conclusions: The research revealed a gene expression signature of tumorigenesis and regional lymph node metastasis in laryngeal squamous cell carcinoma.Of the total, the deregulation of several genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4, EIF3a and RPN2) were potentially associated with disease development and progression. The result will contribute to the understanding of the molecular basis of LSCC and help to improve diagnosis and treatment.
Project description:We investigated whether the miRNA expression could distinguish lung cancers from normal tissues, examining 116 pairs of primary lung cancers with their corresponding adjacent normal lung tissues collected a minimum of 5 cm from the tumor. Our analysis identified a five microRNA classifier could distinguish malignant lung cancer lesions from adjacent normal tissues. SCLC could be distinguished from non small lung cancer by microRNAs profiling. Survival associations were examined with the SCC and adenocarcinoma subtypes. High hsa-miR-31 expression was associated with poor survival in SCC, and the association was confirmed in 20 independent SCC patients by qRT-PCR assays. Overall these findings may help advance the use of microRNA profiling in personalized diagnosis of lung cancers. Key Words: microRNA; lung cancer; microarray; diagnosis; prognosis cancer vs adjacent normal tissues
Project description:Long noncoding RNAs (lncRNAs) play important roles in the tumorigenesis and metastasis of colorectal cancer (CRC). This study used a lncRNA microarray to analyze the aberrant lncRNA expression profiles in CRC tissues compared with paired adjacent normal tissues as well as CRC with regional lymph nodes metastasis compared with CRC without regional lymph nodes metastasis.
Project description:The majority of patients with squamous cell lung cancer (SCC) die because of metastatic disease. The genomic mechanisms underlying this metastatic behaviour are underexposed. We analyzed a cohort of patients with primary squamous cell carcinoma (SCC) using array-based comparative genomic hybridization (aCGH) to identify which genomic aberrations were related metastatic behaviour. The cohort consisted of 34 patients with a follow-up of at least 5 years, including 15 without any metastases, 8 with metastases in regional lymph nodes only, and 11 with metastases exclusively in distant organs within two years after surgery. Common alterations observed in at least 40% of all SCC were gains at 3q13-q29, 5p11-p15, 8q24, 19q13, 20p12-p13, 22q11-q13, and losses at 3p12-p14, 3p24, 4p15, 4q33-q35, 5q14-q23, 5q31-q35, 8p21-p22, 9p21-p24. Amplifications were observed at 2p15-p16, 3q24-q29, 8p11-p12, 8q23-q24, and 12p12, containing candidate oncogenes such as BCL11A, REL, ECT2, PIK3CA, ADAM9, MYC, and KRAS. Gains at 7q36, 8p12, 10q22, 12p12, loss at 4p14 and homozygous deletions at 4q33-q34.1 occurred significantly more frequent in SCC from patients with lymph node metastases. SCC from patients with distant metastases showed a significantly higher frequency of gain at 8q22-q24 and loss of 8p23 and 13q21, and a significantly lower frequency of gain at 2p12 and 2p16 and loss at 11q25 as compared to SCC from patients without metastases. In conclusion, we identified specific genomic aberrations in primary SCC that are related to lymph node or distant metastases. These loci can be further explored for their potential use as predictive or prognostic markers.
Project description:Copy number variation profiling of gastric tissues comparing gastric cancer tissues with matched adjacent noncancerous tissues. Goal was to determine the effects of chromosomal imbalances on gene expression and carcinogenesis or progression. 27 pairs of gastric tissues: gastric cancer tissues vs. matched adjacent noncancerous tissues.
Project description:To further understand the expression pattern of long non-coding RNAs in early stage lung squamous cell carcinoma (SCC), we have employed the Arraystar Human LncRNA Microarray V3.0 profiling as a discovery platform to identify lncRNAs which are differentially expressed in early stage lung SCC. Three pairs of tumor tissues and adjacent normal tissues of early stage lung SCC patients are used for microarray analysis.
Project description:To gain molecular understanding of carcinogenesis, progression, and diversity of gastric cancer, 22 primary human advanced gastric cancer tissues and 8 noncancerous gastric tissues were analyzed by high-density oligonucleotide microarray in this study. Based on expression analysis of approximately 6800 genes, a two-way clustering algorithm successfully distinguished cancer tissues from noncancerous tissues. Subsequently, genes that were differentially expressed in cancer and noncancerous tissues were identified; 162 and 129 genes were highly expressed (P < 0.05) >2.5-fold in cancer tissues and noncancerous tissues, respectively. In cancer tissues, genes related to cell cycle, growth factor, cell motility, cell adhesion, and matrix remodeling were highly expressed. In noncancerous tissues, genes related to gastrointestinal-specific function and immune response were highly expressed. Furthermore, we identified several genes associated with lymph node metastasis including Oct-2 or histological types including Liver-Intestine Cadherin. These results provide not only a new molecular basis for understanding biological properties of gastric cancer, but also useful resources for future development of therapeutic targets and diagnostic markers for gastric cancer. Keywords: other