Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Diabetes and PKM2 affect prognosis in patients with intrahepatic cholangiocarcinoma

ABSTRACT: Diabetes mellitus (DM) is a common disease, but its effect on the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) has not been reported. The aim of the present study was to explore the prognostic significance of diabetes in patients with ICC treated with hepatectomy and to clarify the role of pyruvate kinase M2 (PKM2). A consecutive retrospective cohort of 110 patients with ICC (28 with DM and 82 without DM) who underwent therapeutic hepatectomy was evaluated between January 2006 and January 2011. The clinicopathological characteristics of the two groups and the differences between overall survival (OS) and recurrence-free survival (RFS) were analyzed. The Cox proportional hazards model was further used to identify independent prognostic predictors. PKM2 expression was measured using immunohistochemical staining in tissues collected, after obtaining informed consent. Patients with ICC with DM exhibited significantly lower OS and RFS rates at 1, 3 and 5 years compared with patients with ICC without DM. Cox multivariate analysis revealed that DM was an independent predictor of poor OS and RFS. Additionally, high PKM2 expression was significantly higher in patients with ICC with DM compared with that in patients without DM. Overall, DM was associated with significantly lower OS and RFS rates in patients with ICC. The underlying biological rationale may be attributed to the higher PKM2 expression rate.

SUBMITTER: Fu K

PROVIDER: S-EPMC7517629 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Patients' prognosis of intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma after resection.

Project description:Combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) are classified into one category, but comparison of prognosis of the two carcinomas remains controversial. The aim of the current study was to investigate surgical outcomes for patients with ICC or cHCC-CC who underwent resection in order to elucidate whether the classification of ICC and cHCC-CC is justified. Subjects were 61 patients with ICC and 29 patients with cHCC-CC who underwent liver resection from 2001 to 2017. Clinic-pathological data from the two groups were compared. Tumor number and vascular invasion were independent risk factors for recurrence-free survival (RFS) in both groups (P < .001 for both). Of note, for patients with ICC, tumor cut-off size of 5 cm showed statistical significance in median RFS (>5 cm vs ≤5 cm, 0.5 years vs 4.0 years, P = .003). For patients with cHCC-CC, tumor cut-off size of 2 cm showed statistical significance in median RFS (>2 cm vs ≤2 cm, 0.6 years vs 2.6 years, P = .038). The median RFS of patients with cHCC-CC was 0.9 years (95% confidence interval: 0.3-1.6), which was poorer than that of patients with ICC (1.3 years, 0.5-2.1) (P = .028); the rate of RFS at 5 years was 0% and 37.7% respectively. Our study supports the concept of classifying ICC and cHCC-CC into different categories because of a significant difference in RFS between the two.

| S-EPMC6792494 | biostudies-literature

Clustering of patients with intrahepatic cholangiocarcinoma based on serum periostin may be predictive of prognosis.

Project description:An effective serum biomarker may improve cholangiocarcinoma (CCA) management. Periostin (PN) has been demonstrated to be associated with aggressive CCA. The current study evaluated PN in blood serum for its diagnostic and prognostic potential in patients with CCA. Sera of 68 patients with CCA were collected prior to treatment, and PN levels were measured using an ELISA. Sera from 50 normal controls, 6 patients with benign liver diseases, 2 with hepatocellular carcinoma and 21 with breast cancer were analyzed. Immunohistochemistry of PN in CCA tissues was also investigated. The data were analyzed using the Mann-Whitney U test, Kaplan-Meier log rank tests, Cox proportional hazard regression models and Fisher's exact tests. The median serum PN level in patients with CCA was significantly increased compared with that in healthy controls, patients with benign liver diseases and patients with breast cancer (all P<0.05). Using an optimal threshold value of 94 ng/ml PN, the diagnostic values for CCA compared with other conditions demonstrated a sensitivity level of 0.38 [95% confidence interval (CI), 0.27-0.51], specificity of 0.90 (95% CI, 0.81-0.96), accuracy of 0.66 (95% CI, 0.58-0.74), positive predictive value of 0.76 (95% CI, 0.59-0.89) and negative predictive value of 0.63 (95% CI, 0.53-0.72) (P<0.001). Furthermore, PN stain in stromal fibroblasts in CCA tissues was associated with serum PN levels (P=0.001), and patients with CCA were classified as low (≤94 ng/ml) or high PN (>94 ng/ml) accordingly. High serum and tissue PN levels were significantly associated with reduced survival rate (P<0.001 and P=0.033, respectively). Serum PN was an independent prognostic factor with a hazard ratio of 3.197 (P=0.001). In conclusion, serum PN may be used to divide patients with intrahepatic CCA into high and low PN groups. Elevated serum PN may be utilized as a marker of poor prognosis in patients with CCA.

| S-EPMC5494708 | biostudies-other

Overexpression of FoxM1 predicts poor prognosis of intrahepatic cholangiocarcinoma.

Project description:FoxM1 is an oncoprotein that is significantly overexpressed in many malignancies including hepatocellular carcinoma, but its role in intrahepatic cholangiocarcinoma (ICC) remains unclear. This study explores the expression of FoxM1 in human ICC, its relationships with clinical outcomes, and its role in the proliferation, migration, and invasion of ICC in vitro and in vivo. The results show that FoxM1 was markedly elevated in tumor tissues versus the paired peritumoral tissues. Overexpression of FoxM1 was correlated with multiple tumor nodules, tumor size > 5 cm, positive lymph node metastasis and advanced TNM stage. Cox analysis revealed that overexpression of FoxM1 is an independent prognostic indicator for both the overall survival and disease-free survival of ICC patients after hepatectomy. Furthermore, up/downregulation of FoxM1 markedly promoted/inhibited ICC cell proliferation, migration, and invasion in vitro and in vivo. Bioinformatic analysis indicated that overexpression of FoxM1 resulted in the dysregulation of multiple signaling pathways in ICC, and selected components of some key signaling pathways such as c-Myc signaling were confirmed in vitro. In addition, overexpression of FoxM1 enhanced MMP-9 and MMP-2 protein expression in ICC cells. In conclusion, FoxM1 promotes ICC progression and is a reliable predictor of poor prognosis in ICC.

| S-EPMC6326658 | biostudies-literature

Overexpression of the X-linked ribosomal protein S4 predicts poor prognosis in patients with intrahepatic cholangiocarcinoma.

Project description:X-linked ribosomal protein S4 (RPS4X) has previously been reported to be associated with cisplatin resistance and clinical outcome in bladder and ovarian cancer. However, the value of RPS4X as a diagnostic and prognostic marker in intrahepatic cholangiocarcinoma (ICC) has not yet been investigated. The present study evaluated the expression pattern, and diagnostic and prognostic value of RPS4X in patients with ICC. Retrospective analysis was performed for a total of 201 patients with intrahepatic cholangiocarcinoma, and 8 patients with inflammation of the bile duct. Immunohistochemistry was performed using tissue microarrays to characterize the expression profile of RPS4X. Receiver operating characteristic (ROC) curves, the Kaplan-Meier estimator and Cox regression analysis were applied to evaluate the potential diagnostic and prognostic value of RPS4X in ICC. RPS4X was significantly upregulated in ICC tissues compared with the inflamed bile duct tissues. When differentiating ICC from normal controls, ROC analysis of RPS4X gave an area under the curve value of 0.9030 (sensitivity, 82.59%; specificity, 100%). RPS4X expression was significantly positively correlated with serum alkaline phosphatase levels. Survival analysis demonstrated that RPS4X expression levels were an independent prognostic factor for overall survival. Therefore, RPS4X expression levels may serve as a novel diagnostic and prognostic marker in ICC.

| S-EPMC5494819 | biostudies-other

Identification of macrophage correlated biomarkers to predict the prognosis in patients with intrahepatic cholangiocarcinoma.

Project description:BackgroundIt has been shown that tumor-associated immune cells, particularly macrophages, play a fundamental role in the development and treatment response of intrahepatic cholangiocarcinoma (ICC). However, little is known about macrophages at the single cellular level of ICC patients.MethodsScRNA-seq from Zhang et al. was used in the present study to identify the genes differentially expressed in ICCs. Furthermore, transcriptomic data from TCGA datasets, IHC and flowcytometry from our cohort were used to confirm the findings. Kaplan-Meier and TIDE scores were also used for prognostic analysis and ICB responses.ResultsA significant number of macrophages were found in ICCs as compared to adjacent tissues. We then extracted, processed, and classified the macrophages from the ICCs and adjacent tissues into 12 clusters. Significantly, the macrophages from the ICC exhibited an immunosuppressed state in terms of both signature gene expression and functional enrichment. Furthermore, our results indicate that, of the 10 selective tumor-promoting genes of macrophages, only MMP19 and SIRPα can predict ICB responses in ICCs. Although a higher expression of MMP19 and SIRPα predict a poor prognosis for ICCs without immunotherapy after surgery, patients with high SIRPα expression were more sensitive to immunotherapy, whereas those with high MMP19 expression were not sensitive to immunotherapy. To define the mechanisms, we found that SIRPαhi ICCs exhibited an increased enrichment KEGG pathway of leukocyte transendothelial migration and neutrophil extracellular trap formation. The increased immune cell infiltration will increase sensitivity to immunotherapy.ConclusionCollectively, macrophages are critical to the immune status of ICCs, and MMP19 and SIRPα can predict prognosis and ICB responses for ICCs.

| S-EPMC9497456 | biostudies-literature

High level of CD73 predicts poor prognosis of intrahepatic cholangiocarcinoma.

Project description:Background: Despite recent improvements in the diagnosis and therapy of intrahepatic cholangiocarcinoma (ICC), the prognosis for ICC patients remains poor. Therefore, it is needed to identify new biological indicators for ICC progression. Methods: Immunohistochemistry was engaged to inspect the ecto-5'-nucleotidase (CD73) and CD8 expressions in tissue microarrays including tissues from 140 ICC patients. Then, the association between the level of CD73/CD8 and clinicopathologic characteristics of ICC was analysed. Finally, the prognostic value of CD73 and CD8 levels in ICC patients was assessed by Kaplan-Meier and multivariate and univariate analyses. Results: The CD73 expression was evidently upregulated in ICC tissues compared to the corresponding peritumoral tissues. The elevated CD73 expression was positively related to the lymphatic metastasis (p=0.049). While the level of tumour-infiltrating CD8 T+ cells in tumour tissues was negatively associated with serum AFP (p=0.019), tumor size (p=0.028), and lymphatic metastasis (p=0.039). Additionally, patients with elevated CD73 expression or low tumour-infiltrating CD8+ T cells exhibited shorter overall survival (OS) and higher disease-free survival (DFS) rates than patients with low CD73 expression and/or high tumour-infiltrating CD8+ T cells. Notably, the overexpression of CD73 or low tumour-infiltrating CD8+ T cells was an independent indicator for predicting the OS and DFS of ICC patients. Conclusions: We revealed that CD73 expression and low tumour-infiltrating CD8+T cells are valuable predictors of survival and recurrence in patients with ICC.

| S-EPMC8210563 | biostudies-literature

PKM2 regulates neural invasion of and predicts poor prognosis for human hilar cholangiocarcinoma.

Project description:The therapeutic and prognostic value of the glycolytic enzymes hexokinase, phosphofructokinase, and pyruvate kinase (PK) has been implicated in a variety of cancers, while their roles in treatment of and prognosis for hilar cholangiocarcinoma (HC) remain unclear. In this study, we determined the expression of PKM2 in and its impact on biology and clinical outcome of human HC.The regulation and function of PKM2 in HC pathogenesis was evaluated using human tissues, molecular and cell biology, and animal models, and its prognostic significance was determined according to its impact on patient survival.We found that expression of hexokinase 1 and the M2 splice isoform of PK (PKM2) was upregulated in HC tissues and that this expression correlated with tumor recurrence and outcome. PKM2 expression was increased in HC cases with chronic cholangitis as demonstrated by isobaric tags for relative and absolute quantification. High PKM2 expression was highly correlated with high syndecan 2 (SDC2) expression and neural invasion. PKM2 downregulation led to a decrease in SDC2 expression. Treatment with metformin markedly suppressed PKM2 and SDC2 expression at both the transcriptional and posttranscriptional levels and inhibited HC cell proliferation and tumor growth.PKM2 regulates neural invasion of HC cells at least in part via regulation of SDC2. Inhibition of PKM2 and SDC2 expression contributes to the therapeutic effect of metformin on HC. Therefore, PKM2 is an independent prognostic factor and potential therapeutic target for human HC.

| S-EPMC4650283 | biostudies-literature

Genomic profiling of intrahepatic cholangiocarcinoma: refining prognosis and identifying therapeutic targets.

Project description:BackgroundThe molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection.MethodsMultiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined.ResultsThe majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis.ConclusionsMost somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.

| S-EPMC4324507 | biostudies-literature

CD86<sup>+</sup>/CD206<sup>+</sup> tumor-associated macrophages predict prognosis of patients with intrahepatic cholangiocarcinoma.

Project description:BackgroundAs the main cellular ingredients of tumor microenvironment, tumor-associated macrophages (TAMs) play a vital role in tumor development and progression. Recent studies have suggested that TAMs are sensitive and specific prognostic factors in numerous cancers. The primary purpose of this study is to determine the prognostic significance of TAMs in intrahepatic cholangiocarcinoma (ICC).MethodsImmunohistochemical staining of CD68, CD86 and CD206 were performed in tissue microarrays containing 322 patients, who underwent surgical resection and were pathologically diagnosed with ICC. The prognostic value of CD68, CD86 and CD206 were evaluated by Kaplan-Meier analysis (log-rank test) and nomogram models.ResultsWe demonstrated that the CD86+/CD206+ TAMs model was an independent prognostic index for ICC patients. Patients with low CD86+ TAMs and high CD206+ TAMs infiltration had a markedly worse prognosis and increased risk of post-operative recurrence when compared to high CD86+ TAMs and low CD206+ TAMs intratumoral infiltration. Furthermore, subgroup analysis indicated that the CD86+/CD206+ TAMs model predicted prognosis of ICC patients more powerfully than single macrophage immunomarker. Interestingly, the CD86+/CD206+ TAMs model could further distinguish prognosis of CA-199 negative ICC patients, who were generally presumed to have a more favorable outcome. In order to further perfect the prognostic value of the CD86+/CD206+ TAMs model, we constructed and validated a postoperative nomogram to predict overall survival and recurrence-free survival time in ICC patients.ConclusionsThese findings indicate that the CD86+/CD206+ TAMs model possess potential value as a novel prognostic indicator for ICC patients.

| S-EPMC6982414 | biostudies-literature

High expression of Oct4 and Nanog predict poor prognosis in intrahepatic cholangiocarcinoma patients after curative resection.

Project description:Oct4 and Nanog are reported to promote tumor progression in several cancers, but the effect on intrahepatic cholangiocarcinoma (ICC) is unknown. The aim of our present study was to explore the prognostic role of Oct4 and Nanog on patients with ICC. Immunohistochemistry was used to detect the expression of Oct4 and Nanog in a random cohort of 116 ICC patients, and validated in another independent cohort of 103 patients. Prognostic nomograms were formulated for OS and RFS prediction of ICC patients. Our results showed Oct4 and Nanog highly expressed in ICC tumor tissues and were identified as independent prognostic factors for patients' OS and RFS. Significant positive correlation was found between Oct4 and Nanog expression. Co-expression of Oct4 and Nanog implied the poorest OS and RFS in ICC patients. Our nomograms comprising Oct4 and Nanog achieved better predictive accuracy in training and validation cohorts compared with AJCC 7th edition and LCSGJ stage for OS and RFS prediction. Our study support the high expression of Oct4 and Nanog in ICC implies aggressive tumor behaviors and suggest a poor clinical prognosis, which emerges as valuable biomarkers for identifying patients at high risk after curative resection.

| S-EPMC6400680 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data