PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma
Pentraxin-3 (PTX3) belongs to the pentraxine family, innate immune regulators involved in angiogenesis, proliferation and immune escape in cancer. Here, we evaluated PTX3 tissue expression and serum levels as biomarkers of clear cell renal cell carcinoma (ccRCC) and analyzed the possible role of com...
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| Veröffentlicht in: | Aging (Albany, NY.) NY.), 2020-04, Vol.12 (8), p.7585-7602 |
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| creator | Netti, Giuseppe Stefano Lucarelli, Giuseppe Spadaccino, Federica Castellano, Giuseppe Gigante, Margherita Divella, Chiara Rocchetti, Maria Teresa Rascio, Federica Mancini, Vito Stallone, Giovanni Carrieri, Giuseppe Gesualdo, Loreto Battaglia, Michele Ranieri, Elena |
| description | Pentraxin-3 (PTX3) belongs to the pentraxine family, innate immune regulators involved in angiogenesis, proliferation and immune escape in cancer. Here, we evaluated PTX3 tissue expression and serum levels as biomarkers of clear cell renal cell carcinoma (ccRCC) and analyzed the possible role of complement system activation on tumor site. A 10-year retrospective cohort study including patients undergoing nephrectomy for ccRCC was also performed. PTX3 expression was elevated in both neoplastic renal cell lines and tissues, while it was absent in both normal renal proximal tubular cells (HK2) and normal renal tissues. Analysis of complement system activation on tumor tissues showed the co-expression of PTX3 with C1q, C3aR, C5R1 and CD59, but not with C5b-9 terminal complex. RCC patients showed higher serum PTX3 levels as compared to non-neoplastic patients (p |
| doi_str_mv | 10.18632/aging.103169 |
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Here, we evaluated PTX3 tissue expression and serum levels as biomarkers of clear cell renal cell carcinoma (ccRCC) and analyzed the possible role of complement system activation on tumor site. A 10-year retrospective cohort study including patients undergoing nephrectomy for ccRCC was also performed. PTX3 expression was elevated in both neoplastic renal cell lines and tissues, while it was absent in both normal renal proximal tubular cells (HK2) and normal renal tissues. Analysis of complement system activation on tumor tissues showed the co-expression of PTX3 with C1q, C3aR, C5R1 and CD59, but not with C5b-9 terminal complex. RCC patients showed higher serum PTX3 levels as compared to non-neoplastic patients (p<0.0001). Higher PTX3 serum levels were observed in patients with higher Fuhrman grade (p<0.01), lymph node (p<0.0001), and visceral metastases (p<0.001). Patients with higher PTX3 levels also showed significantly lower survival rates (p=0.002). Our results suggest that expression of PTX3 can affect the immunoflogosis in the ccRCC microenvironment, by activating the classical pathway of CS (C1q) and releasing pro-angiogenic factors (C3a, C5a). The up-regulation of CD59 also inhibits the complement-mediated cellular lysis.</description><identifier>ISSN: 1945-4589</identifier><identifier>EISSN: 1945-4589</identifier><identifier>DOI: 10.18632/aging.103169</identifier><identifier>PMID: 32345771</identifier><language>eng</language><publisher>United States: Impact Journals</publisher><subject>Acute-Phase Proteins ; Biomarkers, Tumor - metabolism ; C-Reactive Protein - biosynthesis ; C-Reactive Protein - genetics ; Carcinoma, Renal Cell - genetics ; Carcinoma, Renal Cell - metabolism ; Carcinoma, Renal Cell - pathology ; DNA, Neoplasm - metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms - genetics ; Kidney Neoplasms - metabolism ; Kidney Neoplasms - pathology ; Male ; Prognosis ; Research Paper ; Retrospective Studies ; Serum Amyloid P-Component - biosynthesis ; Serum Amyloid P-Component - genetics ; Tumor Microenvironment</subject><ispartof>Aging (Albany, NY.), 2020-04, Vol.12 (8), p.7585-7602</ispartof><rights>Copyright © 2020 Netti et al.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-fe078e3090966d5099258ac8d72e85617cddf5c2646b02a0e6fad6c7d985759f3</citedby><cites>FETCH-LOGICAL-c387t-fe078e3090966d5099258ac8d72e85617cddf5c2646b02a0e6fad6c7d985759f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202504/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202504/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32345771$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Netti, Giuseppe Stefano</creatorcontrib><creatorcontrib>Lucarelli, Giuseppe</creatorcontrib><creatorcontrib>Spadaccino, Federica</creatorcontrib><creatorcontrib>Castellano, Giuseppe</creatorcontrib><creatorcontrib>Gigante, Margherita</creatorcontrib><creatorcontrib>Divella, Chiara</creatorcontrib><creatorcontrib>Rocchetti, Maria Teresa</creatorcontrib><creatorcontrib>Rascio, Federica</creatorcontrib><creatorcontrib>Mancini, Vito</creatorcontrib><creatorcontrib>Stallone, Giovanni</creatorcontrib><creatorcontrib>Carrieri, Giuseppe</creatorcontrib><creatorcontrib>Gesualdo, Loreto</creatorcontrib><creatorcontrib>Battaglia, Michele</creatorcontrib><creatorcontrib>Ranieri, Elena</creatorcontrib><title>PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma</title><title>Aging (Albany, NY.)</title><addtitle>Aging (Albany NY)</addtitle><description>Pentraxin-3 (PTX3) belongs to the pentraxine family, innate immune regulators involved in angiogenesis, proliferation and immune escape in cancer. Here, we evaluated PTX3 tissue expression and serum levels as biomarkers of clear cell renal cell carcinoma (ccRCC) and analyzed the possible role of complement system activation on tumor site. A 10-year retrospective cohort study including patients undergoing nephrectomy for ccRCC was also performed. PTX3 expression was elevated in both neoplastic renal cell lines and tissues, while it was absent in both normal renal proximal tubular cells (HK2) and normal renal tissues. Analysis of complement system activation on tumor tissues showed the co-expression of PTX3 with C1q, C3aR, C5R1 and CD59, but not with C5b-9 terminal complex. RCC patients showed higher serum PTX3 levels as compared to non-neoplastic patients (p<0.0001). Higher PTX3 serum levels were observed in patients with higher Fuhrman grade (p<0.01), lymph node (p<0.0001), and visceral metastases (p<0.001). Patients with higher PTX3 levels also showed significantly lower survival rates (p=0.002). Our results suggest that expression of PTX3 can affect the immunoflogosis in the ccRCC microenvironment, by activating the classical pathway of CS (C1q) and releasing pro-angiogenic factors (C3a, C5a). The up-regulation of CD59 also inhibits the complement-mediated cellular lysis.</description><subject>Acute-Phase Proteins</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>C-Reactive Protein - biosynthesis</subject><subject>C-Reactive Protein - genetics</subject><subject>Carcinoma, Renal Cell - genetics</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>DNA, Neoplasm - metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Kidney Neoplasms - genetics</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Kidney Neoplasms - pathology</subject><subject>Male</subject><subject>Prognosis</subject><subject>Research Paper</subject><subject>Retrospective Studies</subject><subject>Serum Amyloid P-Component - biosynthesis</subject><subject>Serum Amyloid P-Component - genetics</subject><subject>Tumor Microenvironment</subject><issn>1945-4589</issn><issn>1945-4589</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1rFTEUhoMotlaXbiVLN1OTySSZbAQp1QoFXVRwF07zMTcySa5JpsV_4M829tZSF4dz4Dy85-NF6DUlp3QWbHwHS0jLKSWMCvUEHVM18WHis3r6qD5CL2r9QYjgfBLP0REb2cSlpMfo99er7wzHbLcVmqu47RwOMW4p-zUvuYaKQ8Jti7ngGEzJLt2EklN0qWFIFncA8L7kJeXagsEeTOus77GHFjpW8W1oO2xWBwUbt664uATroTRQTEg5wkv0zMNa3av7fIK-fTy_OrsYLr98-nz24XIwbJZt8I7I2TGiiBLCcqLUyGcws5Wjm7mg0ljruRnFJK7JCMQJD1YYadXMJVeenaD3B939dh2dNX3BAqvelxCh_NIZgv6_k8JOL_lGy5GMnExd4O29QMk_N1ebjqH-vQWSy1vVI1OCUUK46uhwQPvfai3OP4yhRN-5p-_c0wf3Ov_m8W4P9D-72B-STZpr</recordid><startdate>20200428</startdate><enddate>20200428</enddate><creator>Netti, Giuseppe Stefano</creator><creator>Lucarelli, Giuseppe</creator><creator>Spadaccino, Federica</creator><creator>Castellano, Giuseppe</creator><creator>Gigante, Margherita</creator><creator>Divella, Chiara</creator><creator>Rocchetti, Maria Teresa</creator><creator>Rascio, Federica</creator><creator>Mancini, Vito</creator><creator>Stallone, Giovanni</creator><creator>Carrieri, Giuseppe</creator><creator>Gesualdo, Loreto</creator><creator>Battaglia, Michele</creator><creator>Ranieri, Elena</creator><general>Impact Journals</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200428</creationdate><title>PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma</title><author>Netti, Giuseppe Stefano ; Lucarelli, Giuseppe ; Spadaccino, Federica ; Castellano, Giuseppe ; Gigante, Margherita ; Divella, Chiara ; Rocchetti, Maria Teresa ; Rascio, Federica ; Mancini, Vito ; Stallone, Giovanni ; Carrieri, Giuseppe ; Gesualdo, Loreto ; Battaglia, Michele ; Ranieri, Elena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-fe078e3090966d5099258ac8d72e85617cddf5c2646b02a0e6fad6c7d985759f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute-Phase Proteins</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>C-Reactive Protein - biosynthesis</topic><topic>C-Reactive Protein - genetics</topic><topic>Carcinoma, Renal Cell - genetics</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>Carcinoma, Renal Cell - pathology</topic><topic>DNA, Neoplasm - metabolism</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Kidney Neoplasms - genetics</topic><topic>Kidney Neoplasms - metabolism</topic><topic>Kidney Neoplasms - pathology</topic><topic>Male</topic><topic>Prognosis</topic><topic>Research Paper</topic><topic>Retrospective Studies</topic><topic>Serum Amyloid P-Component - biosynthesis</topic><topic>Serum Amyloid P-Component - genetics</topic><topic>Tumor Microenvironment</topic><toplevel>online_resources</toplevel><creatorcontrib>Netti, Giuseppe Stefano</creatorcontrib><creatorcontrib>Lucarelli, Giuseppe</creatorcontrib><creatorcontrib>Spadaccino, Federica</creatorcontrib><creatorcontrib>Castellano, Giuseppe</creatorcontrib><creatorcontrib>Gigante, Margherita</creatorcontrib><creatorcontrib>Divella, Chiara</creatorcontrib><creatorcontrib>Rocchetti, Maria Teresa</creatorcontrib><creatorcontrib>Rascio, Federica</creatorcontrib><creatorcontrib>Mancini, Vito</creatorcontrib><creatorcontrib>Stallone, Giovanni</creatorcontrib><creatorcontrib>Carrieri, Giuseppe</creatorcontrib><creatorcontrib>Gesualdo, Loreto</creatorcontrib><creatorcontrib>Battaglia, Michele</creatorcontrib><creatorcontrib>Ranieri, Elena</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging (Albany, NY.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Netti, Giuseppe Stefano</au><au>Lucarelli, Giuseppe</au><au>Spadaccino, Federica</au><au>Castellano, Giuseppe</au><au>Gigante, Margherita</au><au>Divella, Chiara</au><au>Rocchetti, Maria Teresa</au><au>Rascio, Federica</au><au>Mancini, Vito</au><au>Stallone, Giovanni</au><au>Carrieri, Giuseppe</au><au>Gesualdo, Loreto</au><au>Battaglia, Michele</au><au>Ranieri, Elena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma</atitle><jtitle>Aging (Albany, NY.)</jtitle><addtitle>Aging (Albany NY)</addtitle><date>2020-04-28</date><risdate>2020</risdate><volume>12</volume><issue>8</issue><spage>7585</spage><epage>7602</epage><pages>7585-7602</pages><issn>1945-4589</issn><eissn>1945-4589</eissn><abstract>Pentraxin-3 (PTX3) belongs to the pentraxine family, innate immune regulators involved in angiogenesis, proliferation and immune escape in cancer. Here, we evaluated PTX3 tissue expression and serum levels as biomarkers of clear cell renal cell carcinoma (ccRCC) and analyzed the possible role of complement system activation on tumor site. A 10-year retrospective cohort study including patients undergoing nephrectomy for ccRCC was also performed. PTX3 expression was elevated in both neoplastic renal cell lines and tissues, while it was absent in both normal renal proximal tubular cells (HK2) and normal renal tissues. Analysis of complement system activation on tumor tissues showed the co-expression of PTX3 with C1q, C3aR, C5R1 and CD59, but not with C5b-9 terminal complex. RCC patients showed higher serum PTX3 levels as compared to non-neoplastic patients (p<0.0001). Higher PTX3 serum levels were observed in patients with higher Fuhrman grade (p<0.01), lymph node (p<0.0001), and visceral metastases (p<0.001). Patients with higher PTX3 levels also showed significantly lower survival rates (p=0.002). Our results suggest that expression of PTX3 can affect the immunoflogosis in the ccRCC microenvironment, by activating the classical pathway of CS (C1q) and releasing pro-angiogenic factors (C3a, C5a). The up-regulation of CD59 also inhibits the complement-mediated cellular lysis.</abstract><cop>United States</cop><pub>Impact Journals</pub><pmid>32345771</pmid><doi>10.18632/aging.103169</doi><tpages>18</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acute-Phase Proteins Biomarkers, Tumor - metabolism C-Reactive Protein - biosynthesis C-Reactive Protein - genetics Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - pathology DNA, Neoplasm - metabolism Female Gene Expression Regulation, Neoplastic Humans Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kidney Neoplasms - pathology Male Prognosis Research Paper Retrospective Studies Serum Amyloid P-Component - biosynthesis Serum Amyloid P-Component - genetics Tumor Microenvironment |
| title | PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma |
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