The “effect” of T staging on resectable metastatic liver colorectal cancer/Early T stage is associated with poor prognosis in patients with metastatic liver colorectal cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE146480 | GEO | 2020/07/06
REPOSITORIES: GEO
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Project description:The “effect” of T staging on resectable metastatic liver colorectal cancer/Early T stage is associated with poor prognosis in patients with metastatic liver colorectal cancer
| PRJNA610640 | ENA
Project description:To evaluate the value of lymph node status of primary tumors in predicting the prognosis of synchronous resectable metastatic colorectal cancer (mCRC).The characteristics of resectable mCRC are substantially different from other cancers, and the prognostic factors of resectable mCRC are still controversial.The data of 2007 patients with mCRC who received resection of the primary tumors and metastatic lesions synchronously were reviewed from the Surveillance, Epidemiology and End-Result database. The Kaplan-Meier method was used to evaluate the capacity of different prognostic factors. Univariate and multivariate logistic regression models were used to evaluate the relationship between the lymph node status and other factors. The mRNA profiles of primary resectable mCRC tumors were obtained by microarray at our center.The median survival times were 50, 36, 32, 27, and 19 months in the N0-stage, N1a-stage, N1b-stage, N2a-stage, and N2b-stage subgroups according to the 7th American Joint Committee on Cancer (AJCC) Tumor Lymph Node Metastasis (TNM) N-classification (P = 0.000), and 40, 29, 22, and 15 months in patients with metastatic lymph node ratio (LNR) <0.25, 0.25-0.49, 0.5-0.74, and ?0.75 subgroups (P = 0.000). In the COX model, the 7th AJCC TNM N-stage and LNR were independent prognostic factors. The mRNA profile was not associated with lymph node involvement.Both the N-stage according to the 7th AJCC TNM staging system and LNR had the capacity to subclassify synchronous resectable mCRC with different prognoses. The lymph node might be integrated into the AJCC staging system as a diagnose-delay prognostic factor for stage IV disease.
| S-EPMC4554134 | biostudies-literature
Project description:Clinically, a considerable portion of patients with early T stage who were supposed to have a low distant metastatic probability were diagnosed with metastatic liver colorectal cancer (CRLM). Our study aims to evaluate the prognostic value of the T stage for metastatic patients and establish a convenient individual assessment model for clinicians to explore preoperative predictors. The mRNA profiles of colorectal tumors (N = 19) were obtained by microarray at our clinical center. A total of 5,618 patients with CRLM from 2010 to 2015 were enrolled for the Surveillance, Epidemiology, and End Results (SEER) database. The cDNA microarray analyses showed that gene expression pattern in the T2N0M1 subgroup was significantly different from the T3/4N0M0 subgroup. In the survival analysis, metastatic patients with T1 stage surprisingly had much poorer prognosis than those with T3/T4 stage. Specifically, metastatic patients with early T stage were observed with higher frequency occurring at the rectum, better differentiation, less metastases in the lymph nodes, and a higher CEA level. Further survival analysis indicated that early T classification was an independent prognostic factor for a poor survival. When the lymph node (N) status was taken into consideration, patients with T1/2N+ had better survival than T1/2N0 patients. A clinical nomogram was constructed based on preoperative factors. The calibration curves showed a good concordance between nomogram prediction and actual observation. In conclusion, CRLM with early T stage had a different biological background. The prognosis of patients at T1/2M1 was poorer than at T3/4M1. More attention should be paid to the surveillance of high-risk factors and the screening of early T stage.
| S-EPMC7314979 | biostudies-literature
Project description:We developed an experimentally derived molecular signature from mouse tumor models that is closely associated with survival of colorectal cancer (CRC) patients. We isolated single cell-derived progenies (SCPs) from the SW480 CRC cell line and compared their metastatic potential in an orthotopic implantation model of murine CRC. We compared the differences in the gene expression profiles of a high metastatic variant SCP51, a low metastatic variant SCP58 and their parent SW480/EGFP.
2011-08-31 | E-GEOD-16934 | biostudies-arrayexpress
Project description:Elevated, tumor-derived extracellular vesicle (tdEV) and circulating tumor cell (CTC) loads in metastatic cancer are associated with poor clinical outcome. Herein, we investigate whether endothelium-derived extracellular vesicles (edEVs) can be detected in the blood of metastatic colorectal cancer (mCRC) patients, and whether those vesicles associate with prognosis. The open-source ACCEPT (Automated CTC Classification, Enumeration, and Phenotyping) software was used to enumerate edEVs, tdEVs, and other objects from digitally stored CellSearch images acquired after CTC and circulating endothelial cell (CEC) enrichment from the blood of 395 mCRC patients before the initiation of a new therapy. Patients had participated in the prospective phase III CAIRO2 study. The presence of edEVs was found 5- to 10-fold higher than CECs. The hazard ratio (HR) (95% CI) of progression-free survival (PFS) for increased CTCs (?3 in 7.5 mL), tdEVs (?40 in 7.5 mL), and edEVs (?287 in 4.0 mL.) was 1.4 (1.1-1.9), 2.0 (1.5-2.6), and 1.7 (1.2-2.5), respectively. The HR of Overall Survival (OS) for increased CTCs, tdEVs and edEVs was 2.2 (1.7-3.0), 2.7 (2.0-3.5), and 2.1 (1.5-2.8), respectively. There was no cut-off value for CECs, leading to a dichotomization of patients with a significant HR. Only tdEVs remained a significant predictor of OS in the final multivariable model.
| S-EPMC7765205 | biostudies-literature
Project description:MYC regulation of a "poor prognosis" metastatic cancer cell state
| PRJNA111899 | ENA
Project description:Tumor microenvironment including fibrosis has a pivotal role in cancer growth and distant metastasis. Fibrosis is a known risk factor for carcinogenesis, but its biological role in disease invasion and metastasis in colorectal cancer (CRC) remains unclear. In particular, there is no report on how fibrosis of metastatic lymph nodes (MLNs) in CRC contributes to prognosis.We reviewed 94 colorectal adenocarcinoma patients with MLNs who underwent colectomy. Both the primary tumors and MLNs were analyzed for alpha-smooth muscle actin (?-SMA) expression and collagen deposition.Higher ?-SMA expression and collagen deposition in MLNs were associated with significantly shorter relapse-free survival and overall survival in CRC patients. ?-SMA expression in MLNs (HR, 1.53; p = 0.034) was independent predictive factor of overall survival in multivariate Cox proportional hazards regression analysis of clinicopathological factors. In the Stage III patient subgroup, ?-SMA expression in MLNs was a strong prognostic marker (HR, 3.01; p = 0.006). On the other hand, higher ?-SMA expression and collagen deposition in primary tumors were associated with short overall survival, but they were not significant factors in multivariate Cox regression analyses. In MLNs, the podoplanin signals co-localized with ?-SMA expression and were confirmed by the dual immunofluorescence staining, implying that the MLN stromal cells were fibroblastic reticular cells.Both high collagen deposition and high ?-SMA expression in MLNs predicted poor prognosis in CRC.
| S-EPMC6049853 | biostudies-other
Project description:PURPOSE:To determine the frequency and prognostic value of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in metastatic colorectal cancer (mCRC) patients in relation to microsatellite instability (MSI) status and MSH3 protein expression. MATERIAL AND METHODS:The frequency of EMAST was evaluated in mCRC patients with MSI tumors and microsatellite stable (MSS) tumors. A literature overview was performed to compare the frequency of EMAST in our study with existing data. Immunohistochemistry for MSH3 was compared with EMAST status. Outcome was studied in terms of overall survival (OS) of mCRC patients with MSI and MSS tumors. RESULTS:EMAST was evaluated in 89 patients with MSI tumors (including 39 patients with Lynch syndrome) and 94 patients with MSS tumors. EMAST was observed in 45.9% (84 out of 183) of patients, with an increased frequency in MSI tumors (79.8% versus 13.8%, p < 0.001). We found no correlation between EMAST and MSH3 protein expression. There was no effect of EMAST on prognosis in patients with MSS tumors, but patients with MSI / non-EMAST tumors had a significantly better prognosis than patients with MSI / EMAST tumors (OS: HR 3.22, 95% CI 1.25-8.30). CONCLUSION:Frequency of EMAST was increased in mCRC patients with MSI tumors, compared to MSS tumors. Our data suggest that the presence of EMAST correlates with worse OS in these patients. There was no effect of EMAST on the prognosis of patients with MSS tumors. A limitation of our study is the small number of patients in our subgroup analysis.
| S-EPMC4401564 | biostudies-literature
Project description:Many genes and mutations have been reported for colorectal cancer (CRC); however, very few have been associated with colorectal cancer liver metastasis (CRLM). We performed gene expression profiling experiments to identify genetic markers for CRLM and elucidate the molecular mechanisms. Microarray experiments were performed on CRC primary tumor samples with or without liver metastasis (LM) using the Affymetrix U133 plus 2.0 GeneChip Array. A new identified gene-scinderin (SCIN) was overexpressed with synchronous LM at both the RNA level evaluated with quantitative real-time PCR and protein level evaluated with immunohistochemistry and also with short overall survival analyzed with Kaplan-Meier method. With multivariate analysis indicated that SCIN served as an independent poor prognostic predictor for CRC patients. Disease-free survival was also significantly lower in SCIN overexpressing CRC patients with metachronous LM. In addition, SCIN knockdown significantly reduced cell proliferation, induced cell cycle arrest, and promoted the expression of some cell cycle apoptosis-related protein. Moreover, the DIAPH1, STAT3, CDK2, CDK4, and EGFR levels were downregulated, whereas CDKN2B and COL4A1 were upregulated in DLD-1-shSCIN cells by microarray analysis compared with DLD-1 shCon cells. These findings revealed that SCIN may serve as an important predictor of CRLM and poor outcome for CRC patients. SCIN may be a potential therapeutic target in human CRC. However, translation of its roles into clinical practice will require further investigation and additional experimental validation.
| S-EPMC6836707 | biostudies-literature
Project description:Through an integrated transcriptome analysis of orthotopic colorectal cancer tumor-bearing mice and sham-operation mice, we showed the distinct immune microenvironment of pre-metastatic liver and identified MDSCs as the dominated cell type mediating pre-metastatic niche formation. MDSCs instead of other immune cell types were highly infiltrated in the pre-metastatic liver when compared with normal liver. Notably, immunosuppressive factors released by MDSCs such as HIF1α, iNOS, TGFβ were significantly up-regulated in the pre-metastatic liver. Increasing immune checkpoint molecules expression also reflected an immunosuppressive condition of pre-metastatic liver. The primary tumor may induce MDSCs accumulation via metabolic mechanism including glycolysis/gluconeogenesis, HIF-1 signaling pathway, and CCL28 chemokine axis. This study depicts the immune cell landscape of pre-metastatic cancer and primary CRC tumor, and provides insights into how MDSCs reshape the pre-metastatic niche facilitating circulating cancer cells colonization.
2020-04-30 | GSE147044 | GEO