ABSTRACT: Membranous Expression of Ectodomain Isoforms of the Epidermal Growth Factor Receptor (EGFR) Predicts Outcome after Chemoradiotherapy of Lymph Node Negative Cervical Cancer
Project description:We compared the prognostic significance of ectodomain isoforms of the epidermal growth factor receptor (EGFR), which lack the tyrosine kinase (TK) domain, with that of the full length receptor and its autophosphorylation status in cervical cancers treated with conventional chemoradiotherapy. We further explored signaling pathways that were correlated with high expression of ectodomain isoforms by gene expression analysis of 110 of the tumors, and validated the results in an independent cohort of 41 tumors.
Project description:We compared the prognostic significance of ectodomain isoforms of the epidermal growth factor receptor (EGFR), which lack the tyrosine kinase (TK) domain, with that of the full length receptor and its autophosphorylation status in cervical cancers treated with conventional chemoradiotherapy. We further explored signaling pathways that were correlated with high expression of ectodomain isoforms by gene expression analysis of 110 of the tumors, and validated the results in an independent cohort of 41 tumors. Pathways associated with the expression of ectodomain isoforms were studied by gene expression analysis with Illumina beadarrays in 110 patients and validated in an independent cohort of 41 patients.
Project description:Gene expression profiling of early stage cervical cancer tumours with and without lymph node metastasis, in order to predict lymph node metastasis before treatment. Subsequently, comparing gene expression profiles between healthy cervical tissue and early stage cervical cancer tissue. Keywords: Disease stage analysis
Project description:Lymph node metastasis(LNM) is the most common metastatic pathway of colorectal cancer (CRC), with a rate of 40.5% to 49.7%. Meanwhile, LNM also is one of the most important prognostic risk factor and often predicts a poor clinical outcome. Therefore, it is necessary to identify relevant genes or elucidate potential molecular mechanisms of LNM in order to develop effective prevention and treatment strategies. The aim of this study is to give an insight into the specific signatures and molecular mechanisms of lymph node metastasis in CRC.
Project description:Gene expression profiling of early stage cervical cancer tumours with and without lymph node metastasis, in order to predict lymph node metastasis before treatment. Subsequently, comparing gene expression profiles between healthy cervical tissue and early stage cervical cancer tissue. Experiment Overall Design: All patients had clinical FIGO stage IB-IIA cervical cancer, the low-risk group (N) included 19 patients without unfavourable prognostic factors (positive lymph nodes, parametrial invasion, positive margins or a combination of unfavourable prognostic factors); the high risk group (P) consisted of 16 patients with lymph node metastasis, who were treated with adjuvant radiation therapy with or without chemotherapy. Healthy cervical tissue biopsies (H) were collected from 5 non-cervical carcinoma patients who underwent hysterectomy for benign reasons. RNA pooled from all tumour tissue samples was used as reference sample. Log-ratios of five technical replicates were used for normalization.
Project description:To investigate the differences in miRNA profiles specially related to lymph node metastasis in cervical cancer, six primary cervical cancer tissues derived from stage І-ІІ patients with (n=3) or without (n=3) lymph node metastasis were collected. The differential expression of seven representative miRNAs (top seven miRNAs included: miR-135-5p, miR-221-3p, miR-25-3p, miR-96-5p, miR-182-5p, miR-183-5p, and miR-144-3p) was verified using qRT-PCR in the same tissues used for microarray analysis.
Project description:High-throughput sequencing was used to detect the expression profile of circRNA in PTMC of lymph node metastasis in lateral cervical region, and RT-qPCR was used to detect the expression of circRNA in cancer tissues and normal tissues adjacent to cancer. The receiver operating characteristic (ROC) curve and the area under ROC curve (AUC) were used to evaluate whether CircRNAs could be used as a biomarker for the diagnosis of thyroid cancer. Bioinformatics was used to predict the PTMC-related ceRNA mechanism of lateral cervical lymph node metastasis.
Project description:Purpose: Presence of pelvic lymph node metastases is the main prognostic factor in early stage cervical cancer patients, primarily treated with surgery. Aim of this study was to identify cellular tumor pathways associated with pelvic lymph node metastasis in early stage cervical cancer. Experimental Design: Gene expression profiles (Affymetrix U133 plus 2.0) of 20 patients with negative (N0) and 19 with positive lymph nodes (N+), were compared with gene sets that represent all 285 presently available pathway signatures. Validation immunostaining of tumors of 274 consecutive early stage cervical cancer patients was performed for representatives of the identified pathways. Results: Analysis of 285 pathways resulted in identification of five pathways (TGF-β, NFAT, ALK, BAD, and PAR1) that were dysregulated in the N0, and two pathways (β-catenin and Glycosphingolipid Biosynthesis Neo Lactoseries) in the N+ group. Class comparison analysis revealed that five of 149 genes that were most significantly differentially expressed between N0 and N+ tumors (P<0.001) were involved in β-catenin signaling (TCF4, CTNNAL1, CTNND1/p120, DKK3 and WNT5a). Immunohistochemical validation of two well-known cellular tumor pathways (TGF-β and β-catenin) confirmed that the TGF-β pathway (positivity of Smad4) was related to N0 (OR:0.20, 95%CI:0.06-0.66) and the β-catenin pathway (p120 positivity) to N+ (OR:1.79, 95%CI:1.05-3.05). Conclusions: Our study provides new, validated insights in the molecular mechanism of lymph node metastasis in cervical cancer. Pathway analysis of the microarray expression profile suggested that the TGF-β and p120-associated non-canonical β-catenin pathways are important in pelvic lymph node metastasis in early stage cervical cancer.
