Dataset Information

Expression of MUC16/CA125 Is Associated with Impaired Survival in Patients with Surgically Resected Cholangiocarcinoma.

ABSTRACT: MUC16/CA125 is associated with cancer proliferation in several tumor entities. The data on MUC16 expression in cholangiocarcinoma (CCA) tissue are very limited. The aim of this study was to assess the MUC16 status and its impact on survival in CCA patients. All the patients with surgically resected CCA that were diagnosed between August 2005 and December 2021 at the University Hospital Frankfurt were retrospectively analyzed. A 7-Mucin biomarker panel was assessed by immunohistochemistry. For overall survival (OS), Kaplan-Meier curves and Cox-regression analyses were performed. Randomly selected intrahepatic cholangiocarcinoma (iCCA) were further processed for differential expression profiling. A total of 168 patients with CCA were classified as MUC16 (-) (66%, n = 111) and MUC16 (+) (34%, n = 57). Subgroup analyses revealed a median OS of 56.1 months (95% CI = 42.4-69.9 months) and 27.4 months (95% CI = 15.8-39.1 months) for MUC16 (-) and MUC16 (+), respectively (p < 0.001). In multivariate analysis, MUC16 (+) (HR = 1.6, 95% CI = 1-2.6, p = 0.032) was an independent risk factor for poor prognosis. Prominently deregulated pathways have been identified following MUC16 expression, overrepresented in cell cycle and immune system exhaustion processes. These findings suggest including MUC16 in clinical routine diagnostics as well as studying its molecular pathways to identify further mechanistic key players.

SUBMITTER: Kinzler MN

PROVIDER: S-EPMC9563928 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression of MUC16/CA125 Is Associated with Impaired Survival in Patients with Surgically Resected Cholangiocarcinoma.

Kinzler Maximilian N MN Schulze Falko F Gretser Steffen S Abedin Nada N Trojan Jörg J Zeuzem Stefan S Schnitzbauer Andreas A AA Walter Dirk D Wild Peter J PJ Bankov Katrin K

Cancers 20220927 19

MUC16/CA125 is associated with cancer proliferation in several tumor entities. The data on MUC16 expression in cholangiocarcinoma (CCA) tissue are very limited. The aim of this study was to assess the MUC16 status and its impact on survival in CCA patients. All the patients with surgically resected CCA that were diagnosed between August 2005 and December 2021 at the University Hospital Frankfurt were retrospectively analyzed. A 7-Mucin biomarker panel was assessed by immunohistochemistry. For ov ...[more]

PMID: 36230626

Similar Datasets

Project description:The CA125 antigen is found in the serum of many patients with serous ovarian cancer and has been widely used as a disease marker. CA125 has been shown to be an independent factor for clinical outcome in this disease. In The Cancer Genome Atlas ovarian cancer project, MUC16 expression levels are frequently increased, and the highest levels of MUC16 expression are linked to a significantly worse survival. To examine the biologic effect of the proximal portion of MUC16/CA125, NIH/3T3 (3T3) fibroblast cell lines were stably transfected with the carboxy elements of MUC16. As few as 114 amino acids from the carboxy-terminal portion of MUC16 were sufficient to increase soft agar growth, promote matrigel invasion, and increase the rate of tumor growth in athymic nude mice. Transformation with carboxy elements of MUC16 was associated with activation of the AKT and ERK pathways. MUC16 transformation was associated with up-regulation of a number of metastases and invasion gene transcripts, including IL-1β, MMP2, and MMP9. All observed oncogenic changes were exclusively dependent on the extracellular "ectodomain" of MUC16. The biologic impact of MUC16 was also explored through the creation of a transgenic mouse model expressing 354 amino acids of the carboxy-terminal portion of MUC16 (MUC16c354). Under a CMV, early enhancer plus chicken β actin promoter (CAG) MUC16c354 was well expressed in many organs, including the brain, colon, heart, kidney, liver, lung, ovary, and spleen. MUC16c354 transgenic animals appear to be viable, fertile, and have a normal lifespan. However, when crossed with p53-deficient mice, the MUC16c354:p53+/- progeny displayed a higher frequency of spontaneous tumor development compared to p53+/- mice alone. We conclude that the carboxy-terminal portion of the MUC16/CA125 protein is oncogenic in NIH/3T3 cells, increases invasive tumor properties, activates the AKT and ERK pathways, and contributes to the biologic properties of ovarian cancer.

Project description:ObjectivePlatelets have been implicated in cancer metastasis and prognosis. No population-based study has been reported as to whether preoperative platelet count directly predicts metastatic recurrence of colorectal cancer (CRC) patients.DesignUsing a well-characterized cohort of 1,513 surgically resected CRC patients, we assessed the predictive roles of preoperative platelet count in overall survival, overall recurrence, as well as locoregional and distant metastatic recurrences.ResultsPatients with clinically high platelet count (≥400 × 10(9)/L) measured within 1 month before surgery had a significantly unfavorable survival (hazard ratio [HR] = 1.66, 95 % confidence interval [CI] 1.34-2.05, P = 2.6 × 10(-6), P(log rank) = 1.1 × 10(-11)) and recurrence (HR = 1.90, 1.24-2.93, P = 0.003, P(log rank) = 0.003). The association of platelet count with recurrence was evident only in patients with metastatic (HR = 2.81, 1.67-4.74, P = 1.1 × 10(-4), P(log rank) = 2.6 × 10(-6)) but not locoregional recurrence (HR = 0.59, 95 % CI 0.21-1.68, P = 0.325, P(log rank) = 0.152). The findings were internally validated through bootstrap resampling (P < 0.01 at 98.6 % of resampling). Consistently, platelet count was significantly higher in deceased than living patients (P < 0.0001) and in patients with metastatic recurrence than locoregional (P = 0.004) or nonrecurrent patients (P < 0.0001). Time-dependent modeling indicated that the increased risks for death and metastasis associated with elevated preoperative platelet counts persisted up to 5 years after surgery.ConclusionOur data demonstrated that clinically high level of preoperative platelets was an independent predictor of CRC survival and metastasis. As an important component of the routinely tested complete blood count panel, platelet count may be a cost-effective and noninvasive marker for CRC prognosis and a potential intervention target to prevent metastatic recurrence.

Dataset Information

Expression of MUC16/CA125 Is Associated with Impaired Survival in Patients with Surgically Resected Cholangiocarcinoma.

Publications

Expression of MUC16/CA125 Is Associated with Impaired Survival in Patients with Surgically Resected Cholangiocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets