Use of Gene Expression Analysis for Discrimination of Primary and Secondary Adenocarcinoma of the Liver

Abstract

Background: Due to late diagnosis and resistance to chemotherapy, most patients with cholangiocarcinoma have an unfavorable prognosis. Despite the use of immunohistochemistry (IHC) in clinical routine, differentiation between intrahepatic cholangiocarcinoma (ICC) and secondary adenocarcinomas of the liver is frequently not clear, leading to false diagnosis and treatment decisions. Methods: Oligonucleotide microarrays (Affymetrix Hu133A^©) were used for gene expression analysis of ICC (n = 11) and secondary adenocarcinomas (colorectal metastases; n = 6). By two-dimensional cluster analysis a specific gene expression profile of these tumors was established and confirmed by real-time polymerase chain reaction and IHC. Results: A total of 338 genes were significantly dysregulated (gene expression/fc ≥2; dysregulation in ≥60%) in both tumor groups. Using two-dimensional cluster analysis a fast, clear, and reproducible differentiation between ICC and colorectal metastases was possible in all cases. As potential biomarkers for differentiation, twelve genes (ICC: KRT7, DBN1, LCTB, LIF, STK17A, PIGF; metastases: TDGF1, HOXA9, TFF3, MYB, ABP1, BCL11A) were detected and will be used for further investigations. Conclusions: A specific gene expression profile for discrimination of primary and secondary adenocarcinoma of the liver could be established. In addition, marker genes for both cancers and their potential use as discrimination markers in clinical routine were also described partially for the first time.

BCL11A Facilitates Cell Proliferation and Metastasis in Neuroblastoma via Regulating the PI3K/Akt Signaling Pathway

“…By analyzing the correlation between gene expression and clinical characteristics in patients with malignant solid tumors, the expression of BCL11A was significantly confirmed to be positively correlated with some tumor metastases, such as breast cancer [ 20 ], liver cancer [ 21 ], laryngeal squamous cell carcinoma [ 22 ], lung squamous cell carcinoma [ 23 ], and so on. Studies found that BCL11A could participate in epithelial-mesenchymal transition and promote breast cancer metastasis by the Wnt/β-catenin signaling pathway [ 8 ].…”

Emerging insights into keratin 7 roles in tumor progression and metastasis of cancers

“…Therefore, careful analysis of immunostaining for CK7 and CK20 is necessary, with consideration of all clinical information, while acknowledging that no tumor demonstrates absolute consistency in its staining with these markers. Hass and colleagues utilized oligonucleotide arrays to differentiate and identify potential biomarkers of intrahepatic cholangiocarcinoma (ICC) and colorectal metastases ( 86 ). Through microarray analysis, numerous dysregulated genes were identified in ICC, with KRT7 being overexpressed in over 80% of ICC cases.…”

“…Through microarray analysis, numerous dysregulated genes were identified in ICC, with KRT7 being overexpressed in over 80% of ICC cases. Interestingly, KRT7 was significantly downregulated in the analyzed tumor probes from metastatic adenocarcinomas, emphasizing the importance of KRT7 in distinguishing primary from metastatic adenocarcinomas of the liver in clinical practice (86). Roy et al aimed to differentiate primary bladder adenocarcinoma (PBA) from metastatic colon adenocarcinoma (MCA), a challenging diagnostic and clinical issue (87).…”

A Multidisciplinary Review of the Roles of Cripto in the Scientific Literature Through a Bibliometric Analysis of its Biological Roles

“…In an approach to identify biomarkers for disease and therapy responses using gene expression arrays, Cripto was one of the markers specifically associated with the metastasis stage, thus discriminating primary intrahepatic cholangiocarcinoma from secondary metastasis [114]. Cripto may also be beneficial as a biomarker to discriminate among diseases that have different treatment approaches.…”