Transcriptional Profiles of Peripheral Blood Leukocytes Identify Patients with Cholangiocarcinoma and Predict Outcome

Abstract

Cholangiocarcinoma (CCA), a slow growing but highly metastatic tumor, is highly prevalent in Northeast Thailand. Specific tests that predict prognosis of CCA remain elusive. The present study was designed to investigate whether peripheral blood leukocyte (PBL) transcriptional profiles might be of use as a prognostic test in CCA patients. Gene expression profiles of PBLs from 9 CCA and 8 healthy subjects were conducted using the Affymetrix HG_U133 Plus 2.0 GeneChip. We indentified informative PBLs gene expression profiles that could reliably distinguish CCA patients from healthy subjects. Of these CCA specific genes, 117 genes were up regulated and 60 were down regulated. The molecular and cellular functions predicted for these CCA specific genes according to the Gene Ontology database indicated differential PBL expression of host immune response and tumor progression genes (EREG, TGF β1, CXCL2, CXCL3, IL-8, and VEGFA). The expression levels of 9 differentially expressed genes were verified in 36 CCA vs 20 healthy subjects. A set of three tumor invasion related genes (PLAU, CTSL and SERPINB2) computed as "prognostic index" was found to be an independent and statistically significant predictor for CCA patient survival. The present study shows that CCA PBLs may serve as disease predictive clinically accessible surrogates for indentifying expressed genes reflective of CCA disease severity.

The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells

“…Here, high expression of PAI-2 was observed and correlated with poor prognosis in CCA patients. PAI-2, previously detected in peripheral blood lymphocytes of CCA patients was proposed as part of a set of markers of independent and statistically significant predictors of patient survival [ 40 ]. We suggest that in addition to lymphocytes, cancer cells and CCFs may be additional sources of PAI-2 released into the microenvironment of CCA tissues.…”

Cholangiocyte senescence caused by lysophosphatidylcholine as a potential implication in carcinogenesis

“…These cytokines have been reported to support the transformation of cells into malignancy and invasiveness . Clinical study investigating peripheral blood leukocyte transcriptional profiles has identified IL‐8 as one of the disease predictive genes for cholangiocarcinoma . Interestingly, the expression of IL‐8 and IL‐6 in isolated cholangiocytes as well as serum level of IL‐8 is proved to be increased in the patients with primary sclerosing cholangitis, which carries a particularly high risk for the development of cholangiocarcinoma with prevalence between 5 and 15% .…”

3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip

“…Furthermore, high infiltration of M2 macrophages in tumor tissues is associated with poor clinical prognosis. [28] Given the tumor-supporting role of TAMs, there is significant interest in reprogramming TAMs from tumorpromoting to tumor-suppressing cells. [29]…”