Circulating miR-106a is a Novel Prognostic and Lymph Node Metastasis Indicator for Cholangiocarcinoma.
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ABSTRACT:
SUBMITTER: Cheng Q
PROVIDER: S-EPMC4632041 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:BackgroundTo investigate the necessity of routine lymph node dissection (LND) in intrahepatic cholangiocarcinoma (ICC) patients without indications of lymph node metastasis (LNM) preoperatively.Methods422 consecutive ICC patients who undergone curative resection from January 2009 to December 2014 were enrolled and categorized as two groups (hepatectomy only or hepatectomy plus LND). Clinicopathologic data was compared between the groups by χ2 or Fisher's exact test. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan-Meier method and differences were analyzed using the log-rank test. Cox regression model was adopted for multivariable analysis.ResultsThe median OS time of all 422 patients was 41.4 months. One-, 3-, and 5-year OS was 67%, 47%, and 35%, respectively. A total of 73 patients had undergone curative resection combined with LND, of whom 20.5% (15/73) were confirmed lymph node positive pathologically. The clinicopathologic characteristics between LND and control groups showed no significant differences. Of the 422 patients, 271 patients had recurrence. The recurrence rates were 65.8% for the LND group and 63.9% for the non-LND group. Survival analysis revealed that, neither the OS (LND vs. non-LND: 32.2 months vs. 46.2 months; p = 0.16) nor the RFS (LND vs. non-LND: 23.1 months vs. 17.0 months; p = 0.09) had significant difference. Multivariate analysis revealed that tumor size, tumor number, carbohydrate antigen19-9, carcinoembryonic antigen, and gamma-glutamyl transpeptidase were independent predictive factors for OS and RFS.ConclusionRoutine LND may not improve survival in resectable ICC patients with negative LNM diagnosis before operation.
| S-EPMC5768365 | biostudies-literature
Project description:BackgroundPancreaticoduodenectomy is the only definitively curative therapy for the long-term survival of distal cholangiocarcinoma patients. Lymph node metastasis is widely accepted as an important prognostic factor for distal cholangiocarcinoma. The latest American Joint Committee on Cancer (AJCC) TNM classification system for distal cholangiocarcinoma has divided the lymph node metastasis patients into N1 and N2 by lymph node metastasis number. However, some studies suggested that the lymph node metastasis ratio may be better than the lymph node metastasis number. Therefore, we develop a program to analyze the correlation between lymph node parameters (lymph node dissection number, lymph node metastasis number, and lymph node metastasis rate) and long-term prognosis.MethodsWe retrospectively reviewed 123 distal cholangiocarcinoma patients after pancreatoduodenectomy from January 2011 to December 2019. The patients were grouped according to lymph node metastases and tumor-free and overall survival rates which were investigated with the Kaplan-Meier analysis. The logistic regression models were used for multivariate analysis to determine the risk factors for lymph node metastases. And the X-tile program was used to calculate the cutoff values for the lymph node parameters that discriminated survival.ResultsThe 1-year, 3-year, and 5-year overall survival rates of patients with distal cholangiocarcinoma after pancreatoduodenectomy were 75.2%, 37.1%, and 31.5%, respectively. And the 1-year, 3-year, and 5-year overall survival rates of patients without and with lymph node metastasis were 83.0%, 50.7%, and 42.5% and 63.5%, 19.0%, and 19.0% (p = 0.000), respectively. Logistic regression showed CA19-9 and portal vein system invasion as independent risk factors for lymph node metastases. The receiver operating characteristic curve showed the optimal cutoff value of CA19-9 to predict the lymph node metastases was 75.5 U/mL. Determined by the X-tile software, the optimal cutoff values of the lymph node dissection number were 24 (p = 0.021), the lymph node metastasis number were 1 and 7 (p = 0.504), and the lymph node metastasis rate were 0.13 (p = 0.002).ConclusionLymph node metastasis is an important factor affecting the long-term survival of distal cholangiocarcinoma patients.CA19-9 and portal vein system invasion are independent risk factors for lymph node metastasis. Besides, the lymph node dissection number and lymph node metastasis rate can predict the long-term survival better than lymph node metastasis number.
| S-EPMC7545845 | biostudies-literature
Project description:Lymph node metastasis is a major prognostic factor for perihilar cholangiocarcinoma (PHC). However, prognostic significance of extent of node dissection, lymph node ratio (LNR), and number and location of positive nodes remain unclear. We aimed to evaluate whether node status, LNR, or number or location of positive nodes are independent factors for staging in PHC and to determine the minimum requirements for node examination.The Surveillance, Epidemiology, and End Results database was used to identify 1116 resected PHCs from 1998 to 2008. The correlation between nodal status and survival was analyzed retrospectively.Lymph node metastasis occurred in 43.4% patients and was an independent predictor for overall survival and cancer-specific survival. No survival benefit was observed for an increasing number of node retrieval in node-positive patients. However, in node-negative patients, ?13 node dissection was of more survival benefit than 3???total lymph node count (TLNC)???12 and TLNC?<?3 (5-year overall survival: 52.8% vs 39.7% vs 26.3%, P?=?0.001; 5-year cancer-specific survival: 60.6% vs 46.3% vs 30.0%, P?=?0.001). No difference in survival between patients with regional and distant node involvement was found. Survival for patients with greater than three positive nodes was significantly worse than that for those with three or less (relative ratio: 1.466, P?=?0.001). And patients with LNR?>?0.27 also had unfavorable prognosis (relative ratio: 1.376, P?=?0.001).We determined that to adequately assess nodal status of this life-threatening disease, 13 or more nodes retrieval should be considered. Number of positive nodes and LNR rather than location of metastatic nodes may be defined as parameters for staging of PHC.
| S-EPMC4732906 | biostudies-literature
Project description:Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes. Currently, the treatment and prognosis for CCA are mostly poor. Recently, we have reported that coiled-coil domain containing 25 (CCDC25) protein level in the sera may be a diagnostic marker for CCA. Subsequently, we identified three binding proteins of CCDC25 and found that kallikrein-11 (KLK11) expression was highest among those binding proteins. In this study, we investigated CCDC25 and KLK11 expression in CCA and adjacent normal tissues (n = 18) using immunohistochemistry. The results demonstrated that the expressions of CCDC25 and KLK11 in CCA tissues were both significantly higher than the adjacent tissues (p < 0.001 and p = 0.001, respectively). Then, using GEPIA bioinformatics analysis, KLK11 mRNA was significantly overexpressed in CCA tumor tissues compared with normal tissues (p < 0.05). Moreover, CCDC25 expression was positively correlated with KLK11 expression in CCA with lymph node metastasis (p = 0.028, r = 0.593). An analysis for the interaction of KLK11 with CCDC25 and other proteins, using STRING version 11.0, revealed that CCDC25 and KLK11 correlated with metastasis-related proteins. In addition, Kaplan-Meier survival curve analysis revealed that a high expression of KLK11 was associated with the poor prognosis of CCA. In conclusion, KLK11 is, as a binding protein for CCDC25, possibly involved in the metastatic process of CCA. KLK11 may be used as a prognostic marker for CCA.
| S-EPMC8196963 | biostudies-literature
Project description:(1) Background: Lymph node (LN) status is an indubitable prognostic factor for survival among colon cancer patients. MicroRNAs (miRNAs) have been implicated in the development and progression of many cancers and are potential biomarkers for cancer diagnosis and prognosis. Therefore, we validated candidate biomarkers using circulating miRNAs by analyzing the plasma miRNA concentrations from patients with colon cancer to predict LN metastasis. (2) Methods: This study included 79 blood samples from patients diagnosed with colon cancer. The NanoString assay was used for screening, and TaqMan miRNA assays for quantitative real-time polymerase chain reaction (RT-PCR) test was used for validation. In a discovery set, we compared the expression of 800 circulating miRNAs in 24 samples (stage 0/I/IIA versus IIIB/IIIC). For validation, a total 79 samples were tested using quantitative RT-PCR. (3) Results: In the discovery set, 10 candidate circulating miRNAs were detected (4 up-regulated miRNAs: miR-323a-3p, miR-382-5p, miR-29a-3p, and miR-376a-3p; 6 down-regulated miRNAs: miR-26a-5p, let-7g-5p, miR-15b-5p, miR-142-3p, miR-374a-5p, and let-7b-5p). In the validation set, higher expression of three circulating miRNAs (miR-323a-3p, miR-382-5p, and miR-376a-3p) was significantly associated with LN metastasis (p = 0.0063, 0.0107, and 0.0022). (4) Conclusions: High expression of circulating miR-323a-3p, miR-382-5p, and miR-376a-3p was significantly associated with LN metastasis in colon cancer patients. These miRNAs could be circulating biomarker candidates that predict the presence of LN metastasis.
| S-EPMC7912296 | biostudies-literature
Project description:Lymph nodes are important peripheral immune organs in which numerous important immune responses occur. During the process of lymphatic metastasis, lymph nodes are also sites through which tumor cells must pass. Therefore, it is essential to develop a drug delivery system that can specifically transfer immunostimulatory medicine into lymph nodes to block lymphatic metastasis. Here, we developed a nucleic acid drug delivery system containing cationic agarose (C-agarose) and CpG oligodeoxynucleotides. C-agarose has a high affinity for Siglec-1 on the surface of lymph node sinus macrophages, which have a high specificity for targeting lymph nodes. Subcutaneous implantation of C-agarose+CpG gel caused the accumulation of CpG in the lymph node sinus macrophages and generated antitumor immune responses in the lymph node. C-agarose+CpG gel treatment decreased the metastasis size in the tumor-draining lymph node (TDLN) and lung metastatic nodules and suppressed tumor growth in both a mouse 4T1 breast cancer model and a B16F10 melanoma model. On this basis, this study proposes a nonsurgical invasive lymph node targeting immunotherapy concept that may provide a new approach for antitumor metastasis.
| S-EPMC6529739 | biostudies-literature
Project description:Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8+ T cell infiltration and better prognoses in ICC patients. Mechanistically, β-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, β-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic β-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or β-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.
| S-EPMC11208581 | biostudies-literature
Project description:Within the multicenter SUCCESS trial, we investigated the association of plasma microRNAs with different subtypes of invasive breast cancer.Six miRs (miR-16, miR-27a, miR-107, miR-130a, miR-132 and miR-146a) were selected from microarray profiling and further validated in plasma of 111 breast cancer patients before and after chemotherapy and 46 healthy women by quantitative real-time PCR.Plasma levels of miR-16 (p = 0.0001), miR-27a (p = 0.039) and miR-132 (p = 0.020) were higher in breast cancer patients before chemotherapy than healthy women. With the exception of miR-16, the increased levels of miR-27a (p = 0.035) and miR-132 (p = 0.025) decreased after chemotherapy to those observed in healthy women. Levels of miR-16 (p = 0.019), miR-107 (p = 0.036), miR-130a (p = 0.027) and miR-146a (p = 0.047) were different between lymph node -positive and -negative patients, while the levels of miR-130a (p = 0.001) and miR-146a (p = 0.025) also differed between HER2-positive and -negative status. Estrogen-receptor negative tumors displayed higher concentrations of circulating miR-107 than their counterparts (p = 0.035). However, overexpression of miR-107 in MCF-7 cells did not downregulate estrogen receptor protein. Altered expression levels of miR-107 influenced the migration and invasion behavior of MCF-7 and MDA-MB-231 cells.Our data indicate differential concentrations of plasma miR-16, miR-107, miR-130a and miR-146a in different breast cancer subtypes, suggesting a potential role of these miRs in breast cancer biology and tumor progression.
| S-EPMC4537022 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC) with a low 5-year survival rate, which may be associated with the presence of metastatic tumors at the time of diagnosis, especially lymph node metastasis (LNM). This study aimed to construct a LNM-related gene signature for predicting the prognosis of patients with LUAD.MethodsRNA sequencing data and clinical information of LUAD patients were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Samples were divided into metastasis (M) and nonmetastasis (NM) groups based on LNM status. Differentially expressed genes (DEGs) between M and NM groups were screened, and then WGCNA was applied to identify key genes. Furthermore, univariate Cox and LASSO regression analyses were conducted to construct a risk score model, and the predictive performance of model was validated by GSE68465, GSE42127, and GSE50081. The protein and mRNA expression level of LNM-associated genes were detected by human protein atlas (HPA) and GSE68465.ResultsA prognostic model based on eight LNM-related genes (ANGPTL4, BARX2, GPR98, KRT6A, PTPRH, RGS20, TCN1, and TNS4) was developed. Patients in the high-risk group had poorer overall survival than those in the low-risk group, and validation analysis showed that this model had potential predictive value for patients with LUAD. HPA analysis supported the upregulation of ANGPTL4, KRT6A, BARX2, RGS20 and the downregulation of GPR98 in LUAD compared with normal tissues.ConclusionOur results indicated that the eight LNM-related genes signature had potential value in the prognosis of patients with LUAD, which may have important practical implications.
| S-EPMC9904923 | biostudies-literature
Project description:AimWe have previously reported the existence of lymph nodes surrounding the thoracic duct ( TDLN) and transthoracic esophagectomy (TTE) with thoracic duct (TD) resection increased the number of lymph nodes (LNs) retrieved. The current study aims to evaluate the prognostic impact of TDLN metastasis in esophageal cancer patients subdivided by its location and comparing the patients' survival with those with extra-regional LN metastasis.MethodsPatients who underwent TTE with TD resection for esophageal squamous cell carcinoma (ESCC) were reviewed. Patients were classified into those with or without TDLN metastasis, and clinicopathological factors were compared between groups. TDLN was further divided into TDLN-Ut/Mt/Lt based on the location in the mediastinum. The relapse-free survival (RFS) and overall survival (OS) were compared between groups.ResultsOf 232 patients, TDLN metastasis was observed in 17 (7%). RFS and OS were significantly worse in the TDLN metastasis group. TDLN metastasis was shown to be an independent prognostic factor for RFS and OS in the multivariate analysis. The negative prognostic impact of TDLN metastasis was evident in TDLN-Mt/Lt. The RFS and OS of patients with TDLN metastasis were almost identical to those with positive LN metastasis in extra-regional LNs.ConclusionTDLN metastasis was proven to be a strong prognostic indicator. Although the TDLN has been included in the classification of regional LN in the current staging systems, it could be independently classified from the current regional LNs. Given that neoadjuvant therapy has been a standard, we might need to introduce adjuvant therapy when TDLN metastasis is observed.
| S-EPMC8164460 | biostudies-literature