Global miRNA expression in small bowel neuroendocrine tumors (SBNET) and their lymph node/liver metastases
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE70534 | GEO | 2016/09/05
SECONDARY ACCESSION(S): PRJNA288959
REPOSITORIES: GEO
Similar Datasets
Project description:miRNA profiling study revealing novel miRNAs deregulated in SBNET compared to normal small bowel and identifying miRNA that are differentially regulated with disease progression. These have the potential to be used in the future for patient stratification and treatment response monitoring. Dataset 1 Matched samples from 15 SBNET patients (47 samples) were used to determine a miRNA profile for SBNET and identify potential markers of disease progression. Patient numbers: 1-15. Dataset 2 A second dataset of miRNA expression data (43 samples) containing an increased number of liver metastases, as well as SBNET and lymph node metastases. Patient numbers: B9-B140, controls: C1, C2.
2016-09-05 | E-GEOD-70534 | biostudies-arrayexpress
Project description:Background: The prognostic significance of the lymph node (LN) classification for small bowel neuroendocrine tumors (SBNETs) remains unknown. The aim of the present study was to evaluate and compare the prognostic assessment of different LN staging systems. Methods: Patients with SBNETs were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The X-tile program was used to determine the cutoff value of the resected lymph nodes (RLNs), negative lymph nodes (NLNs), lymph node ratio (LNR), and the log odds of positive lymph nodes (LODDS). Survival analyses were performed using Kaplan-Meier curves with log-rank test. Logistic regression analysis was used to evaluate the differences between different periods. Univariate and multivariate Cox proportional hazards models were used to assess the prognostic value of different LN staging systems on cause-specific survival (CSS). The relative discriminative abilities of the different LN staging systems were assessed using the Akaike information criterion (AIC) and the Harrell consistency index (HCI). Result: A total of 3,680 patients were diagnosed with SBNETs between 1988 and 2014 from the SEER database. A significant difference over time (1988-1999 vs. 2000-2014) was seen in age (P <0.001), tumor differentiation (P <0.001), T stage (P <0.001), and RLN (P <0.001) subgroups. Multivariate Cox survival analysis identified that LN status stratified by the number of RLNs, NLNs, LNR, and LODDS all predicted CSS in patients with SBNETs (all P <0.05), whereas the number of positive lymph nodes (PLNs) failed (P = 0.452). When assessed using categorical variables, LODDS staging systems showed the best prognostic performance (HCI: 0.766, AIC: 7,575.154) in the whole population. Further analysis based on different RLNs after eliminating the missing data showed that when the RLNs are <12, the LODDS (HCI: 0.769, AIC: 1,088.731) maintained the best prognostic performance as well when the RLNs are ?12 (HCI: 0.835, AIC: 825.692). Among patients with LNR scores of 0 or 1, there was a residual heterogeneity of outcomes that were better stratified and characterized by the LODDS. Conclusion: LODDS was a better predicator of survival when LN status was stratified as a categorical variable and should be considered when assessing the prognosis of patients with SBNETs to allow a more reliable means to stratify patient survival.
| S-EPMC7358303 | biostudies-literature
Project description:ObjectivesTo evaluate the relationship between deep inguinal lymph node metastasis (ILNM) and pelvic lymph node metastasis (PLNM) and explore the prognostic value of deep ILNM in penile squamous cell carcinoma (PSCC).Materials and methodsThe records of 189 patients with ILNM treated for PSCC were analysed retrospectively. Logistic regression models were used to test for predictors of PLNM. Cox regression was performed in univariable and multivariable analyses of cancer-specific survival (CSS). CSS was compared using Kaplan-Meier analyses and log rank tests.ResultsPLNM were observed in 53 cases (28.0%). According to logistic regression models, only deep ILNM (OR 9.72, p<0.001) and number (≥3) of metastatic inguinal lymph nodes (ILNs) (OR 2.36, p=0.03) were independent predictors of PLNM. The incidences of PLNM were 18% and 19% with negative deep ILNM and extranodal extension (ENE); and 76% and 42% with positive deep ILNM and ENE, respectively. The accuracy of deep ILNM, ENE, bilateral involvement and number (≥3) of ILNMs for predicting PLNM were 81.0%, 65.6%, 63.5% and 67.2%, respectively. The CSS was significantly different in patients with positive and negative deep ILNM (median 1.7 years vs not reached, p<0.01). Patients who presented with deep ILNM had worse CSS (median 3.8 years vs not reached, p<0.01) in those with negative PLNs.ConclusionsDeep ILNM is the most accurate factor for predicting PLNM in PSCC according to our data. We recommend that patients with deep ILNM should be referred for pelvic lymph node dissection. Involvement of deep ILNs indicates poor prognosis. We propose that patients with metastases of deep ILNs may be staged as pN3.
| S-EPMC8479104 | biostudies-literature
Project description:BackgroundTo validate the prognostic impacts of the left gastric artery lymph node (No. 7 LN) metastasis and investigate whether the No. 7 LN metastasis should be considered as the predictive LN for extra-gastric LN metastases.MethodsBetween January 2003 and December 2011, a total of 1,586 patients who underwent R0 gastrectomy were retrospected. Patients with LN metastases were divided into three groups: (I) patients with only peri-gastric LN metastases (peri-gastric group); (II) patients with peri-gastric and only No. 7 LN metastases (No. 7 group); and (III) patients with other extra-gastric LN metastases (extra-gastric group). Propensity score matching (PSM) was adopted to accurately evaluate prognoses of all patients after surgery.ResultsOf 1,586 patients, 235 (14.82%) were pathologically identified to present with the No. 7 LN metastases. Patients with the No. 7 LN metastases presented the significantly lower survival rate both before and after adjustment by pTNM stage, compared to those without the No. 7 LN metastases. Patients in the No. 7 group were identified to present the significant lower survival rate than those in the peri-gastric group, and to present the similar median overall survival (OS) to those in the extra-gastric group. In addition, patients with extra-gastric LN except No. 7 LN metastases failed to show any superiority of survival outcomes, compared with those with extra-gastric LN metastases including the No. 7 LN metastasis.ConclusionsThe No. 7 LN metastases had the crucial survival implications. Nevertheless, the No. 7 LN failed to be considered as the predictive LN for the extra-gastric LN metastases in gastric cancer (GC).
| S-EPMC7327347 | biostudies-literature
Project description:BackgroundPatients with breast cancer presenting with single lymph node metastasis (from a sentinel node) experience prolonged survival compared to patients with multiple lymph node metastases (≥3). However, little information is available on the genetic and immunological characteristics of breast cancer metastases within the regional lymph nodes as they progress from the sentinel lymph node (SLN) downstream to multiple regional lymph nodes (MLNs).MethodsGenomic profiling was performed using a next-generation sequencing panel covering 520 cancer-related genes in the primary tumour and metastatic lymph nodes of 157 female patients with breast cancer. We included primary tumours, metastatic lymph nodes and adjacent clinically normal lymph nodes (20 patients from the SLN group and 28 patients from the MLNs group) in the whole transcriptome analysis.FindingsThe downstream metastatic lymph nodes (P = 0.029) and the primary breast tumours (P = 0.011) had a higher frequency of PIK3CA mutations compared to the SLN metastasis. We identified a distinct group of 14 mutations from single sentinel node metastasis and a different group of 15 mutations from multiple nodal metastases. Only 4 distinct mutations (PIK3CA, CDK4, NFKBIA and CDKN1B) were conserved in metastases from both lymph node settings. The tumour mutational burden (TMB) was significantly lower in single nodal metastasis compared to the paired primary breast cancer (P = 0.0021), while the decline in TMB did not reach statistical significance in the MLNs group (P = 0.083). In the gene set enrichment analysis, we identified 4 upregulated signatures in both primary tumour and nodal metastases from the MLNs group, including 3 Epithelial-mesenchymal transition(EMT) signatures and 1 angiogenesis signature. Both the CD8/Treg ratio and the CD8/EMT ratio were significantly higher in adjacent normal lymph nodes from patients with a single metastasis in the SLN compared with samples from the MLNs group (P = 0.045 and P = 0.023, respectively). This suggests that the immune defence from the MLNs patients might have a less favourable microenvironment, thus permitting multiple lymph nodes metastasis.InterpretationSingle lymph node metastases and multiple lymph node metastases have significant differences in their molecular profiles and immune profiles. The findings are associated with more aggressive tumour characteristics and less favourable immune charactoristics in patients with multiple nodal metastases compared to those with a single metastasis in the sentinel node.FundingThis work was supported by funds from High-level Hospital Construction Project (DFJH201921), the National Natural Science Foundation of China (81902828 and 82002928), the Fundamental Research Funds for the Central Universities (y2syD2192230), and the Medical Scientific Research Foundation of Guangdong Province (B2019039).
| S-EPMC8399410 | biostudies-literature
Project description:OBJECTIVESTo identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer.SUMMARY BACKGROUND DATALimited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics.METHODSData on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques.RESULTSpN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5?cm) and 20 for longer, poorly differentiated ones.CONCLUSIONSIn esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.
| S-EPMC5405457 | biostudies-literature
Project description:BackgroundMyofibroblasts have an important role in regulating the normal colorectal stem cell niche. While the activation of myofibroblasts in primary colorectal cancers has been previously described, myofibroblast activation in lymph node metastases has not been described before.MethodsParaffin-embedded lymph node sections from patients with macrometastases, micrometastases and isolated tumour cells were stained to identify myofibroblasts and to characterise the distribution of different cell types in tumour-containing lymph nodes. The extent of myofibroblast presence was quantified and compared with the size of the metastasis and degree of proliferation and differentiation of the cancer cells.ResultsWe show substantial activation of myofibroblasts in the presence of colorectal metastases in lymph nodes, which is intimately associated with glandular structures, both in micro- and macrometastases. The degree of activation is positively associated with the size of the metastases and the proportion of Ki67+ve cancer cells, and negatively associated with the degree of enterocyte differentiation as measured by CK20 expression.ConclusionThe substantial activation of myofibroblasts in tumour-containing lymph nodes strongly suggests that these metastatic cancer cells are still significantly dependent on their microenvironment. Further understanding of these epithelial-mesenchymal interactions could lead to the development of new therapies in metastatic disease.
| S-EPMC3670500 | biostudies-literature
Project description:Small Bowel Neuroendocrine Tumors (Carcinoid Tumors)
| PRJNA185380 | ENA
Project description:Purpose: Recent studies have highlighted the existence of subclones in tumors. Lymph nodes are generally the first location of metastasis for most solid epithelial tumors, including colorectal cancer. We sought to understand the genetic origin of lymph node metastasis in colorectal cancer by evaluating the relationship between colorectal cancer subclones present in primary tumors and lymph nodes.Experimental Design: A total of 33 samples from seven colorectal cancers, including two or three spatially disparate regions from each primary tumor and one to four matched lymph nodes for each tumor, underwent next-generation whole-exome DNA sequencing, Affymetrix OncoScan SNP arrays, and targeted deep confirmatory sequencing. We performed mapping between SNPs and copy number events from the primary tumor and matched lymph node samples, allowing us to profile heterogeneity and the mutational origin of lymph node metastases. The computational method PyClone was used to define subclones within each tumor. The method Clonality Inference in Tumors Using Phylogeny (CITUP) was subsequently used to infer phylogenetic relationships among subclones.Results: We found that there was substantial heterogeneity in mutations and copy number changes among all samples from any given patient. For each patient, the primary tumor regions and matched lymph node metastases were each polyclonal, and the clonal populations differed from one lymph node to another. In some patients, the cancer cell populations in a given lymph node originated from multiple distinct regions of a tumor.Conclusions: Our data support a model of lymph node metastatic spread in colorectal cancer whereby metastases originate from multiple waves of seeding from the primary tumor over time. Clin Cancer Res; 24(9); 2214-24. ©2017 AACRSee related commentary by Gerlinger, p. 2032.
| S-EPMC5932232 | biostudies-other
Project description:Genetic diversity among metastases is poorly understood but contains important information about disease evolution at secondary sites. Here we investigate inter- and intra-lesion heterogeneity for two types of metastases that associate with different clinical outcomes: lymph node and distant organ metastases in human colorectal cancer. We develop a rigorous mathematical framework for quantifying metastatic phylogenetic diversity. Distant metastases are typically monophyletic and genetically similar to each other. Lymph node metastases, in contrast, display high levels of inter-lesion diversity. We validate these findings by analyzing 317 multi-region biopsies from an independent cohort of 20 patients. We further demonstrate higher levels of intra-lesion heterogeneity in lymph node than in distant metastases. Our results show that fewer primary tumor lineages seed distant metastases than lymph node metastases, indicating that the two sites are subject to different levels of selection. Thus, lymph node and distant metastases develop through fundamentally different evolutionary mechanisms.
| S-EPMC7343611 | biostudies-literature