Elevated expression of cyclooxygenase-2 is a negative prognostic factor for overall survival in intrahepatic cholangiocarcinoma.
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ABSTRACT:
SUBMITTER: Schmitz KJ
PROVIDER: S-EPMC1888720 | biostudies-other | 2007 Feb
REPOSITORIES: biostudies-other
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Project description:PURPOSE:To evaluate factors associated with survival following transarterial 90Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). METHODS:This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan-Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival. RESULTS:46 patients were included (19 male, 27 female), median age 62.5 years (range 29-88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1-12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume (p = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced liver disease was observed. DISCUSSION:Survival after 90Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.
| S-EPMC7020033 | biostudies-literature
Project description:PurposeThe role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy.Patients and methodsIn this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort.ResultsFrom 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34-0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50-0.65 vs. HR 0.63, 95% CI 0.57-0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29-0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46-0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43-0.80; p < 0.001).ConclusionIn patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy.
| S-EPMC10278501 | biostudies-literature
Project description:BackgroundPeritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocarcinoma (ICC) which may be derived from small bile duct cells or liver progenitor cells (LPCs) was known to us. However, whether peritumoral DR is also related to non-mucin-producing ICCs remains to be investigated.MethodsForty-seven patients with non-mucin-producing ICC were eventually included in the study and clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and α-smooth muscle actin were performed in tumor and peritumor liver tissues.ResultsA significant correlation existed between peritumoral DR and local inflammation and fibrosis. (r = 0.357, 95% CI, 0.037-0.557; P = 0.008 and r = 0.742, 95% CI, 0.580-0.849; P < 0.001, respectively). Patients with obvious peritumoral DR had high recurrence rate (81.8% vs 56.0%, P = 0.058) and poor overall and disease-free survival time (P = 0.01 and P = 0.03, respectively) comparing with mild peritumoral DR. Compared with the mild peritumoral DR group, the proliferation activity of LPCs/ cholangiocytes was higher in obvious peritumoral DR, which, however, was not statistically significant. (0.43 ± 0.29 vs 0.28 ± 0.31, P = 0.172). Furthermore, the correlation analysis showed that the DR grade was positively related to the portal/septalα-SMA level (r = 0.359, P = 0.001).ConclusionsPeritumoral DR was associated with local inflammation and fibrosis. Patients with non-mucin-producing ICC having obvious peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC. However, the mechanism should be further investigated.
| S-EPMC7532600 | biostudies-literature
Project description:The purpose of this study was to investigate the association of tumor tissue and plasma miR-146a/b expressions with the clinicopathological properties and overall survival (OS) in surgical patients with intrahepatic cholangiocarcinomas (ICC).Eighty-seven patients with ICC were enrolled. Tumor tissue and plasma sample were collected and miR-146a/b expressions were assessed by quantitative polymerase chain reaction (qPCR). The median follow-up duration was 31 months, and the last follow-up date was January 2017.miR-146a (P?<?.001) and miR-146b (P?=?.006) expressions in tumor tissue were positively associated with that in plasma. Tissue miR-146a was negatively correlated with age (P?=?.036), poor differentiation (P?=?.020), N stage (P?=?.020), and TNM stage (P?=?.007), as well as ECOG performance (P?=?.008), whereas plasma miR-146a was inversely associated with N stage (P?=?.003), TNM stage (P?=?.003), and ECOG performance (P?=?.011). Moreover, tissue miR-146b was negatively correlated with gender (P?=?.043) and T stage (P?=?.047). Kaplan-Meier curves suggested that high expression of tissue miR-146a (P?<?.001) and plasma miR-146a (P?=?.029) were correlated with prolonged OS. Nevertheless, no association of miR-146b expression in tumor tissue (P?=?.187) and plasma (P?=?.336) with OS was discovered. Univariate analysis indicated that both tissue miR-146a (P?<?.001) and plasma miR-146a (P?=?.035) could predict better OS, whereas multivariate analysis revealed that only tissue miR-146a (P?=?.001) high expression was an independent factor for prolonged OS.Both plasma and tissue miR-146a expression correlated with favorable OS, whereas only tissue miR-146a was an independent prognostic biomarker in surgical patients with ICC.
| S-EPMC5682774 | biostudies-other
Project description:ImportanceIntrahepatic cholangiocarcinoma is an aggressive hepatobiliary malignant neoplasm characterized by local progression and frequent metastasis. Definitive local therapy to the liver in the setting of metastatic intrahepatic cholangiocarcinoma may improve overall survival.ObjectiveTo compare the overall survival of patients with metastatic intrahepatic cholangiocarcinoma treated with chemotherapy alone vs chemotherapy with definitive liver-directed local therapy.Design, setting, and participantsThis cohort study used the National Cancer Database to identify 2201 patients with metastatic intrahepatic cholangiocarcinoma diagnosed between January 2004 and December 2014 who received chemotherapy with or without hepatic surgery or external beam radiation to a dose 45 Gy or higher. Multiple imputation, Cox proportional hazards, propensity score matching, and landmark analysis were used to adjust for confounding variables. Analyses were performed between September 2018 and February 2019.ExposuresChemotherapy alone and chemotherapy with liver-directed surgery or radiation.Main outcomes and measuresOverall survival.ResultsA total of 2201 patients (1131 [51.4%] male; median [interquartile range] age, 63 [55-71] years) who received chemotherapy alone (2097 [95.3%]) or chemotherapy with liver-directed local therapy (total, 104 [4.7%]; surgery, 76 [73.1%]; radiation, 28 [26.9%]) were identified. Patients treated with chemotherapy alone had larger median (interquartile range) primary tumor size (7.0 [4.4-10.0] cm vs 5.6 [4.0-8.3] cm; P = .048) and higher frequency of lung metastases (383 [25.9%] vs 7 [6.7%]; P = .004). Patients treated with liver-directed local therapy had higher frequency of distant lymph node metastases (34 [32.7%] vs 528 [25.2%]; P = .045). Liver-directed local therapy was associated with higher overall survival compared with chemotherapy alone on multivariable analysis (hazard ratio [HR], 0.60; 95% CI, 0.48-0.74; P < .001). A total of 208 patients treated with chemotherapy alone were propensity score matched with 104 patients treated with chemotherapy plus liver-directed local therapy. Liver-directed local therapy continued to be associated with higher overall survival (HR, 0.57; 95% CI, 0.44-0.74; P < .001), which persisted on landmark analysis at 3 months (HR, 0.61; 95% CI, 0.47-0.79; log-rank P < .001), 6 months (HR, 0.68; 95% CI, 0.50-0.92; log-rank P = .01), and 12 months (HR, 0.68; 95% CI, 0.47-0.98; log-rank P = .04).Conclusions and relevanceIn this study, the addition of hepatic surgery or irradiation to chemotherapy was associated with higher overall survival when compared with chemotherapy alone in patients with metastatic intrahepatic cholangiocarcinoma. These findings may be valuable given the paucity of available data for this disease and should be validated in an independent cohort or prospective study.
| S-EPMC6745054 | biostudies-literature
Project description:Intrahepatic cholangiocarcinoma (ICC) remains a highly heterogeneous disease with poor prognosis. Tumor-infiltrating lymphocytes were predictive in various cancers, but their prognostic value in ICC is less clear. A total of 168 ICC patients who had received liver resection were enrolled and assigned to the derivation cohort. Sixteen immune markers in tumor and peritumor regions were examined by immunohistochemistry. A least absolute shrinkage and selection operator model was used to identify prognostic markers and to establish an immune signature for ICC (ISICC ). An ISICC -applied prediction model was built and validated in another independent dataset. Five immune features, including CD3peritumor (P) , CD57P , CD45RAP , CD66bintratumoral (T) and PD-L1P , were identified and integrated into an individualized ISICC for each patient. Seven prognostic predictors, including total bilirubin, tumor numbers, CEA, CA19-9, GGT, HBsAg and ISICC , were integrated into the final model. The C-index of the ISICC -applied prediction model was 0.719 (95% CI, 0.660-0.777) in the derivation cohort and 0.667 (95% CI, 0.581-0.732) in the validation cohort. Compared with the conventional staging systems, the new model presented better homogeneity and a lower Akaike information criteria value in ICC. The ISICC -applied prediction model may provide a better prediction performance for the overall survival of patients with resectable ICC in clinical practice.
| S-EPMC7156843 | biostudies-literature
Project description:Intrahepatic cholangiocarcinoma (iCCA) arises along the peripheral bile ducts and is often accompanied by a tumor microenvironment (TME) high in extracellular matrices (ECMs). In this study, we aimed to evaluate whether an ECM-rich TME favors iCCA progression. We identified ITGA2, which encodes collagen-binding integrin α2, to be differentially-expressed in iCCA tumors compared with adjacent normal tissues. Elevated ITGA2 is also positively-correlated with its ligand, collagen type I. Increased ITGA2 expression and its role in collagen type I binding was validated in vitro using four iCCA cell lines, compared with a non-cancerous, cholangiocyte cell line. Robust interaction of iCCA cells with collagen type I was abolished by either ITGA2 depletion or integrin α2β1-selective inhibitor treatment. In a phenotypic study, collagen type I significantly enhances clonogenic growth of HuCCA-1 and HuCCT-1 cells by three and sixfold, respectively. Inhibition of integrin α2 expression or its activity significantly blocks collagen type I-induced colony growth in both cell lines. Taken together, our data provide mechanistic evidence that collagen type I promotes growth of iCCA colonies through integrin α2 suggesting that the collagen type I-integrin α2 axis could be a promising target for cancer prevention and a therapeutic opportunity for this cancer.
| S-EPMC9794692 | biostudies-literature
Project description:Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary epithelial tumor with poor prognosis. There are increasing evidences that long non-coding RNAs (lncRNAs) are dysregulated in multifarious tumors, revealing potential significant role of lncRNAs in tumorigenesis.We used the ICC dataset retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus database to obtain the lncRNAs expression profiles and identify potential prognostic lncRNAs for predicting the prognosis in ICC. Univariate and multivariate Cox regression analyses were performed to construct a prognostic index (PI). Furthermore, coexpression analysis and functional assessment were performed to initially investigate the function of these prognostic lncRNAs.A total of 255 differentially expressed lncRNAs (DElncRNAs) were identified among two RNA sequencing dataset of a total 63 ICC patients with 98 samples using R platform. Thirteen of 255 DElncRNAs were identified as prognostic lncRNAs and used for a PI. Patients with high PI were associated with poor prognostic (P = .0064), and the Cox regression showed consistent result (P = .042). The time-dependent receiver operating characteristic analysis showed the PI performed well in ICC survival prediction with an area under curve of 0.921, 0.801, and 0.717 for 1-, 3-, and 5-year survival, respectively.In conclusion, we included 13 identified prognostic DElncRNAs and constructed a prognostic signature/PI. ICC patient with higher PI was associated with poorer prognosis. However, the clinical role as well as biological functions of constructed PI and these prognostic DElncRNAs need to be verified in future study.
| S-EPMC7220432 | biostudies-literature
Project description:BackgroundSex-determining region Y-box (SRY-box) containing gene 9 (SOX9) expression confers cancer stem cell features. However, SOX9 function in intrahepatic cholangiocarcinoma (iCCA) is unknown. This study investigated the effects and underlying mechanisms of SOX9 in iCCA.MethodsSOX9 expression in 59 iCCA patients was examined by immunohistochemistry. The association between SOX9 expression and clinical outcome was evaluated. Gene signature and biological functions of SOX9 in iCCA were examined in vitro.ResultsiCCA patients with high SOX9 expression had shorter survival time than those with low SOX9. In patients receiving chemotherapy, median survival time in patients with low and high levels of SOX9 were 62 and 22 months, respectively. In vitro, gemcitabine increased SOX9 expression in iCCA cells. When SOX9 was knocked down, gemcitabine-induced apoptosis was markedly increased. Silencing SOX9 significantly inhibited gemcitabine-induced phosphorylation of checkpoint kinase 1, a key cell cycle checkpoint protein that coordinates the DNA damage response and inhibited the expression of multidrug resistance genes. Microarray analyses showed that SOX9 knockdown in CCA cells altered gene signatures associated with multidrug resistance and p53 signalling.ConclusionsSOX9 governs the response of CCA cells to chemotherapy. SOX9 is a biomarker to select iCCA patients eligible for efficient chemotherapy.
| S-EPMC6265288 | biostudies-literature
Project description:BackgroundCalpain small subunit 1 (Capn4) has been shown to correlate with the metastasis/invasion of hepatocellular carcinoma. This study aimed to investigate the role of Capn4 in intrahepatic cholangiocarcinoma (ICC).MethodsCapn4 expression was measured in 33 ICC tissues by quantitative real-time polymerase chain reaction and western blot. The role of Capn4 in the migration, invasion and proliferation of ICC cells and matrix metalloproteinase 2 (MMP2) expression were assessed after Capn4 depletion by specific small interfering RNA. Capn4 expression was further examined by immunohistochemistry in a tissue microarray consisting of 140 ICC patients and 13 normal liver tissues, and the prognostic role of Capn4 in ICC was evaluated by Kaplan-Meier and Cox regression analyses.ResultsCapn4 expression was significantly higher in the ICC tissues compared to the peritumor tissues. Capn4 down-regulation impaired the migration/invasion ability of HCCC-9810 and QBC939 cells in vitro and decreased MMP2 expression. Capn4 overexpression significantly correlated with the presence of lymphatic metastasis of ICC (p = 0.026) and the tumor-node-metastasis (TNM) stage (p = 0.009). The postoperative 2- and 5-year overall survivals in patients with Capn4(low) were higher than those in the Capn4(high) group. The cumulative recurrence rate in patients with Capn4(low) was much lower than in the Capn4(high) group. Multivariate analysis showed that Capn4 overexpression was an independent prognostic marker in ICC.ConclusionsCapn4 overexpression was implicated in ICC metastasis/invasion, and Capn4 overexpression may be used as a molecular therapeutic target for ICC.
| S-EPMC3551843 | biostudies-literature