A Complex Network of Tumor Microenvironment in Human High-Grade Serous Ovarian Cancer

Most high-grade serous ovarian cancer (HGSOC) patients develop recurrent disease after first-line treatment, frequently with fatal outcome. This work aims at studying the molecular biology of both primary and recurrent HGSOC. Gene expression profiles of matched primary and recurrent fresh-frozen tum...

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Veröffentlicht in:Clinical cancer research 2017-12, Vol.23 (24), p.7621-7632
Hauptverfasser: Kreuzinger, Caroline, Geroldinger, Angelika, Smeets, Dominiek, Braicu, Elena Ioana, Sehouli, Jalid, Koller, Julia, Wolf, Andrea, Darb-Esfahani, Silvia, Joehrens, Korinna, Vergote, Ignace, Vanderstichele, Adriaan, Boeckx, Bram, Lambrechts, Diether, Gabra, Hani, Wisman, G Bea A, Trillsch, Fabian, Heinze, Georg, Horvat, Reinhard, Polterauer, Stephan, Berns, Els, Theillet, Charles, Cacsire Castillo-Tong, Dan
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container_end_page 7632
container_issue 24
container_start_page 7621
container_title Clinical cancer research
container_volume 23
creator Kreuzinger, Caroline
Geroldinger, Angelika
Smeets, Dominiek
Braicu, Elena Ioana
Sehouli, Jalid
Koller, Julia
Wolf, Andrea
Darb-Esfahani, Silvia
Joehrens, Korinna
Vergote, Ignace
Vanderstichele, Adriaan
Boeckx, Bram
Lambrechts, Diether
Gabra, Hani
Wisman, G Bea A
Trillsch, Fabian
Heinze, Georg
Horvat, Reinhard
Polterauer, Stephan
Berns, Els
Theillet, Charles
Cacsire Castillo-Tong, Dan
description Most high-grade serous ovarian cancer (HGSOC) patients develop recurrent disease after first-line treatment, frequently with fatal outcome. This work aims at studying the molecular biology of both primary and recurrent HGSOC. Gene expression profiles of matched primary and recurrent fresh-frozen tumor tissues from 66 HGSOC patients were obtained by RNA sequencing. Clustering analyses and pairwise comparison of the profiles between matched samples and subsequent functional alignment were used for the identification of molecular characteristics of HGSOC. Both primary and recurrent HGSOC samples presented predominant gene expression differences in their microenvironment, determined by a panel of genes covering all major pathways of immune activation together with a number of genes involved in the remodeling of extracellular matrix and adipose tissues. Stratifying tumor tissues into immune active and silent groups, we further discovered that although some recurrent tumors shared the same immune status as their primary counterparts, others switched the immune status, either from silent to active or active to silent. Interestingly, genes belonging to the B7-CD28 immune checkpoint family, known for their major role as negative regulators of the immune response, were overexpressed in the immune active tumors. Searching for potential tumor antigens, , a member of the carcinoembryonic antigen family, was found to be significantly overexpressed in immune active tissues in comparison with the silent ones. The results illustrate the complexity of the tumor microenvironment in HGSOC and reveal the molecular relationship between primary and recurrent tumors, which have multiple therapeutic implications. .
doi_str_mv 10.1158/1078-0432.CCR-17-1159
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This work aims at studying the molecular biology of both primary and recurrent HGSOC. Gene expression profiles of matched primary and recurrent fresh-frozen tumor tissues from 66 HGSOC patients were obtained by RNA sequencing. Clustering analyses and pairwise comparison of the profiles between matched samples and subsequent functional alignment were used for the identification of molecular characteristics of HGSOC. Both primary and recurrent HGSOC samples presented predominant gene expression differences in their microenvironment, determined by a panel of genes covering all major pathways of immune activation together with a number of genes involved in the remodeling of extracellular matrix and adipose tissues. Stratifying tumor tissues into immune active and silent groups, we further discovered that although some recurrent tumors shared the same immune status as their primary counterparts, others switched the immune status, either from silent to active or active to silent. 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genetics</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - immunology</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Patients</subject><subject>Regulators</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Sequence Analysis, RNA</subject><subject>Tissues</subject><subject>Tumor Microenvironment - genetics</subject><subject>Tumor Microenvironment - immunology</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctOwzAQRS0E4v0JIEtsYBHw-BHHyyoCilSoBGVtOakNgSQuTlPg73FUyoKNbV2fGc3ci9AJkEsAkV0BkVlCOKOXef6YgEyiqrbQPgghE0ZTsR3fG2YPHXTdGyHAgfBdtEczJSnhch89j3Dum0Vtv_CDXX768I69w7O-8QHfV2Xwtl1VwbeNbZe4avG4b0w8q5fX5DaYucVPNvi-w9OVCVX8yU1b2nCEdpypO3v8ex-i55vrWT5OJtPbu3w0SUouyTJhQIjJDJdGlakqDHPASKYcd2URdUtKZdLCUCZcCillis2lk2CokMQ5VrBDdLHu-2pqvQhVY8K39qbS49FEDxqhVCrO6Qoie75mF8F_9LZb6qbqSlvXprVxAw2Kp5yJTAzo2T_0zfehjZtEKmMcor0yUmJNRZe6Llj3NwEQPWSkB__14L-OGWmQg6pi3elv975o7PyvahMK-wGi6YqA</recordid><startdate>20171215</startdate><enddate>20171215</enddate><creator>Kreuzinger, Caroline</creator><creator>Geroldinger, Angelika</creator><creator>Smeets, Dominiek</creator><creator>Braicu, Elena Ioana</creator><creator>Sehouli, Jalid</creator><creator>Koller, Julia</creator><creator>Wolf, Andrea</creator><creator>Darb-Esfahani, Silvia</creator><creator>Joehrens, Korinna</creator><creator>Vergote, Ignace</creator><creator>Vanderstichele, Adriaan</creator><creator>Boeckx, Bram</creator><creator>Lambrechts, Diether</creator><creator>Gabra, Hani</creator><creator>Wisman, G Bea A</creator><creator>Trillsch, Fabian</creator><creator>Heinze, Georg</creator><creator>Horvat, Reinhard</creator><creator>Polterauer, Stephan</creator><creator>Berns, Els</creator><creator>Theillet, Charles</creator><creator>Cacsire Castillo-Tong, Dan</creator><general>American Association for Cancer Research Inc</general><general>American Association for Cancer Research</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-3429-302X</orcidid></search><sort><creationdate>20171215</creationdate><title>A Complex Network of Tumor Microenvironment in Human High-Grade Serous Ovarian Cancer</title><author>Kreuzinger, Caroline ; Geroldinger, Angelika ; Smeets, Dominiek ; Braicu, Elena Ioana ; Sehouli, Jalid ; Koller, Julia ; Wolf, Andrea ; Darb-Esfahani, Silvia ; Joehrens, Korinna ; Vergote, Ignace ; Vanderstichele, Adriaan ; Boeckx, Bram ; Lambrechts, Diether ; Gabra, Hani ; Wisman, G Bea A ; Trillsch, Fabian ; Heinze, Georg ; Horvat, Reinhard ; Polterauer, Stephan ; Berns, Els ; Theillet, Charles ; Cacsire Castillo-Tong, Dan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-3100a8a47a9c69ba3f13089f4fcba8ae0c9a6ba235f6162393d7f71a2570ff3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adipose tissue</topic><topic>Adult</topic><topic>Aged</topic><topic>Antigen (tumor-associated)</topic><topic>Antigens</topic><topic>Antigens, Neoplasm - 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Interestingly, genes belonging to the B7-CD28 immune checkpoint family, known for their major role as negative regulators of the immune response, were overexpressed in the immune active tumors. Searching for potential tumor antigens, , a member of the carcinoembryonic antigen family, was found to be significantly overexpressed in immune active tissues in comparison with the silent ones. The results illustrate the complexity of the tumor microenvironment in HGSOC and reveal the molecular relationship between primary and recurrent tumors, which have multiple therapeutic implications. .</abstract><cop>United States</cop><pub>American Association for Cancer Research Inc</pub><pmid>28972047</pmid><doi>10.1158/1078-0432.CCR-17-1159</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3429-302X</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adipose tissue
Adult
Aged
Antigen (tumor-associated)
Antigens
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
B7 antigen
Cancer
Carcinoembryonic antigen
CD28 antigen
Cell Line, Tumor
Clustering
Complexity
Cystadenocarcinoma, Serous - genetics
Cystadenocarcinoma, Serous - immunology
Cystadenocarcinoma, Serous - pathology
Experimental design
Extracellular matrix
Female
Gene expression
Gene Expression Regulation, Neoplastic
Gene sequencing
Genes
Humans
Immune checkpoint
Immune response
Immune status
Immune system
Life Sciences
Medical treatment
Middle Aged
Molecular biology
Neoplasm Grading
Neoplasm Recurrence, Local - genetics
Neoplasm Recurrence, Local - pathology
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - immunology
Ovarian Neoplasms - pathology
Patients
Regulators
Ribonucleic acid
RNA
Sequence Analysis, RNA
Tissues
Tumor Microenvironment - genetics
Tumor Microenvironment - immunology
Tumors
title A Complex Network of Tumor Microenvironment in Human High-Grade Serous Ovarian Cancer
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