Project description:The aim of this study was to evaluate whether microRNA profiles of grade 1 – 2 or 3 endometrioid adenocarcinomas can be related to nodal status and used as a tool to adapt surgical staging in early-stage EC. MicroRNA expression were assessed in twelve formalin-fixed paraffin-embedded (FFPE) EC primary tumors with positive lymph node and in 36 FFPE EC primary tumors with negative lymph node, matched for grade, stage and lymphovascular space involvement status.
Project description:Endometrial cancer is the most common gynecological cancer worldwide. In women from developed countries, endometrial cancer is usually detected after the age of 60 years. Nearly 90% of the diagnosed cases are sporadic, while 10% are attributed to genetic factors. Thus, it is necessary to develop a diagnostic platform. Currently, the lymph node status is a major prognostic factor in assessing endometrial cancer. However, despite its high sensitivity, it is still in debate. In order to increase its selectivity and specificity, in-depth proteomic study has been performed on patients sentinel lymph node (SNL) samples and on grade I to grade III endometrial carcinoma (EC) samples. We identified specific markers of bad diagnosis that clearly correlate SNL to EC i.e. PRSS3, PTX3, ASS1, YBX2, RBM25, MUC5B. These markers have also been detected in TCGA. By contrast, we also detected good prognosis markers for the overall survival such as CD74, GOLM1, SLC9A3R2, SP100 proteins. Markers for EC and SNL cancer-grading have also been identified. Taken together, it is now possible to propose a novel approach for molecular diagnosis, prognosis and patient’s stratification in EC which will be of excellent utility in therapeutic decision.
Project description:Both the univariate analysis and multivariate analysis showed that the status of primary lymph node was the strongest predict factor. The subgroup analysis confirmed that the lymph node metastasis was associated to worse prognosis only in stage T3 and T4, rather than in stage T1 and T2. We firstly proposed the hypothesis that the status of lymph node reflected delayed diagnose of the disease, rather than the biological behavior of “seed”. The mRNA profile showed that there was minimal difference between lymph node positive and negative subgroups. The status of lymph node reflected delayed diagnose of the disease, rather than the biological behavior of “seed”.
Project description:Predictors built from gene expression data accurately predict ER, PR, and HER2 status, and divide tumor grade into high-grade and low-grade clusters; intermediate-grade tumors are not a unique group. In contrast, gene expression data cannot be used to predict tumor size or lymphatic-vascular invasion. Experiment Overall Design: Microarray data from the tumors of 129 patients were analyzed for the ability to predict biomarkers (ER, PR, HER2), histologic features (grade and lymphatic-vascular invasion), and stage-related information (tumor size and lymph node metastasis). Multiple statistical predictors were used and the prediction accuracy determined by error rates of prediction and by dimensional scaling and visualization of the states under study. Models to predict lymph node metastasis were built by combinations of molecular, histologic and anatomic features.
Project description:The biological tumor samples (ie, breast tumor specimens) consisted of freshly frozen breast tumors from a population-based cohort of 315 women representing 65% of all breast cancers resected in Uppsala County, Sweden, from January 1, 1987 to December 31, 1989. Estrogen receptor status was determined by biochemical assay as part of the routine clinical procedure. An experienced pathologist determined the Elston-Ellis grades of the tumors, classifying the tumors into low, medium and high-grade tumors. The clinico-pathological characteristics accompanying each tumor include p53 status, ER status, tumor grade, lymph node status and patient age. Experiment Overall Design: All tumor specimens were assessed on U133 A and B arrays.
Project description:The biological tumor samples (ie, breast tumor specimens) consisted of freshly frozen breast tumors from a population-based cohort of 315 women representing 65% of all breast cancers resected in Uppsala County, Sweden, from January 1, 1987 to December 31, 1989. Estrogen receptor status was determined by biochemical assay as part of the routine clinical procedure. An experienced pathologist determined the Elston-Ellis grades of the tumors, classifying the tumors into low, medium and high-grade tumors. The clinico-pathological characteristics accompanying each tumor include p53 status, ER status, tumor grade, lymph node status and patient age. Keywords: Tumor sample comparisons
Project description:Identifying the exact molecules associated with CRC metastasis may be crucial to understand the process, which might also be translated to the diagnosis and treatment of CRC. In this study, we investigate the association of microRNA expression patterns with the lymph node metastasis of colorectal cancer. To investigate the association of microRNA expression patterns with the lymph node metastasis of colorectal cancer, eight primary colorectal cancer tissues derived from stage II–III colorectal cancer patients with (n = 4) or without (n = 4) lymph node metastasis were collected and the miRNA expression profiles of them were determined using Agilent miRNA microarray. Different miRNA expression profiles were identified in CRC tissues between lymph node metastasis positive and negative group.
Project description:Identification of Predictive Markers for Lymph Node Metastasis in Clinically Early-Stage Endometrial Cancer Patientses with/without Lymph Node Metastasis in Clinically Early-Stage Endometrial Cancer
Project description:Current prognostic factors are insufficient for precise risk-discrimination in breast cancer patients with low grade breast tumors, which, in disagreement with theoretical prognosis, occasionally form early lymph node metastasis. To identify markers for this group of patients, we employed iTRAQ-2DLC-MS/MS proteomics to 24 lymph node positive and 24 lymph node negative grade 1 luminal A primary breast tumors. Another group of 48 high-grade tumors (luminal B, triple negative, Her-2 subtypes) was also analyzed to investigate marker specificity for grade 1 luminal A tumors. From the total of 4405 proteins identified (FDR<5%), the top 65 differentially expressed together with 30 previously identified and control markers were analyzed also at transcript level. Increased levels of carboxypeptidase B1 (CPB1), PDZ and LIM domain protein 2 (PDLIM2) and ring finger protein 25 (RNF25) were associated specifically with lymph node positive grade 1 tumors, whereas stathmin 1 (STMN1) and thymosin beta 10 (TMSB10) associated with aggressive tumor phenotype also in high grade tumors at both protein and transcript level. For CPB1, these differences were also observed by immunohistochemical analysis on tissue microarrays. Upregulation of putative biomarkers in lymph node positive (vs. negative) luminal A tumors was validated by gene expression analysis of an independent published dataset (N=343) for CPB1 (p=0.00155), PDLIM2 (p=0.02027) and RELA (p=0.00015). Moreover, statistically significant connections with patient survival were identified in another public dataset (N=1678). Our findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-κB pathway and changes in cell survival and cytoskeleton. These putative biomarkers have potential to identify the specific minor sub-population of breast cancer patients with low grade tumors who are at higher than expected risk of recurrence and who would benefit from more intensive follow-up and may require more personalized therapy.
Project description:The aim of this study was to evaluate whether micro-RNA signature in tumor tissues from low-risk Endometrial Cancer women can be correlated with the occurrence of recurrences MicroRNA expression was assessed by chip analysis in 7 formalin-fixed paraffin-embedded (FFPE) LREC primary tumors from women whose follow up showed recurrences (R+) and in 14 FFPE LREC primary tumors from women whose follow up did not show any recurrence (R-), matched for grade and age.