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How does the tumor microenvironment play a role in hepatobiliary tumors?

ABSTRACT: The tumor microenvironment (TME) is defined as the structural and dynamic network of cellular and non-cellular interactions between malignant cells and the surrounding non-malignant matrix. Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are two of the most challenging gastrointestinal malignancies. Despite clinical advancements in understanding tumor biology and growth of the chemotherapeutic industry, there have been no corresponding improvements in prognosis and overall survival of HCC and PDAC. Both of these cancers have a very intimate relationship with their surrounding environment; the TME is thought to actively participate in initiating and sustaining these malignancies. Individual TME constituents play a vital role in chemoresistance and recurrence after surgery and have been established as independent prognostic factors. This review article will highlight the diverse structural components, key signaling pathways, and extracellular matrices of HCC and PDAC and discuss their crosstalk with tumor cells to promote growth and metastasis. The article will also summarize the latest laboratory and clinical research based on therapeutic targets identified within the TME of both HCC and PDAC.

SUBMITTER: Kamil F

PROVIDER: S-EPMC5848044 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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How does the tumor microenvironment play a role in hepatobiliary tumors?

Kamil Fathima F Rowe Julie H JH

Journal of gastrointestinal oncology 20180201 1

The tumor microenvironment (TME) is defined as the structural and dynamic network of cellular and non-cellular interactions between malignant cells and the surrounding non-malignant matrix. Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are two of the most challenging gastrointestinal malignancies. Despite clinical advancements in understanding tumor biology and growth of the chemotherapeutic industry, there have been no corresponding improvements in prognosis and ove ...[more]

PMID: 29564184

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Project description:BackgroundSIGLEC family genes can also be expressed on tumor cells in different cancer types, and though it has been found that SIGLEC genes expressed by immune cells can be exploited by tumors to escape immune surveillance, functions of tumor derived SIGLEC expression in tumor microenvironment (TME) were barely investigated, which could play roles in cancer patients' survival.MethodsUsing bioinformatic analysis, mutation status of SIGLEC family genes was explored through the cBioPortal database, and expression of them in different tumors was explored through the UALCAN database. The GEPIA database was used to compare SIGLEC family genes' mRNA between cancers and to generate a highly correlated gene list in tumors. A KM-plotter database was used to find the association between SIGLEC genes and survival of patients. The associations between SIGLEC family genes' expression, immune infiltration, and immune regulators' expression in TME were generated and examined by the TIMER 2.0 database; the differential fold changes of SIGLEC family genes in specific oncogenic mutation groups of different cancer types were also yielded by TIMER 2.0. The networks of SIGLEC family genes and highly correlated genes were constructed by the STRING database, and gene ontology and pathway annotation of SIGLEC family highly correlated genes were performed through the DAVID database.ResultsSIGLEC family genes were highly mutated and amplified in melanoma, endometrial carcinoma, non-small cell lung cancer, bladder urothelial carcinoma, and esophagogastric adenocarcinoma, while deep deletion of SIGLEC family genes was common in diffuse glioma. Alteration of SIGLEC family genes demonstrated different levels in specific tumors, and oncogenic mutation in different cancer types could influence SIGLEC family genes' expression. Most SIGLEC family genes were related to patients' overall survival and progression free survival. Also, tumor derived SIGLEC family genes were related to tumor immune cell infiltration and may regulate TME by influencing chemokine axis.ConclusionOur computational analysis showed SIGLEC family genes expressed by tumor cells were associated with tumor behaviors, and they may also influence TME through chemokine axis, playing vital roles in patients' survival. Further experiments targeting tumor derived SIGLEC family genes are needed to confirm their influences on tumor growth, metastasis, and immune environment regulation.

Dataset Information

How does the tumor microenvironment play a role in hepatobiliary tumors?

Publications

How does the tumor microenvironment play a role in hepatobiliary tumors?

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