Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure
Triple negative breast cancers (TNBC) are an aggressive molecular subtype of breast carcinoma (BC) identified by the lack of receptor expression for estrogen, progesterone, & human epidermal growth factor receptor‐2. Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zin...
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| Veröffentlicht in: | Journal of cellular physiology 2024-04, Vol.239 (4), p.e31203-n/a |
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| creator | Saravanan, Roshni Balasubramanian, Vaishnavi Sundaram, Sandhya Dev, Bhawna Vittalraj, Pavithra Pitani, Ravi Shankar Shanmugasundaram, Gouthaman Rayala, Suresh Kumar Venkatraman, Ganesh |
| description | Triple negative breast cancers (TNBC) are an aggressive molecular subtype of breast carcinoma (BC) identified by the lack of receptor expression for estrogen, progesterone, & human epidermal growth factor receptor‐2. Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zinc (Zn) transporter known to be overexpressed in few cancer types including BCs. Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN‐LIV1A for treatment of TNBC patients. Though LIV1 also has a role in modulating immune cells by its differential transport of Zn, a correlation between the tumor cell expression of LIV1 and immune cell infiltrations were scantily reported. Further adequate baseline data on LIV1 expression in other populations have not been documented. Our objective was to screen a large Indian cohort of TNBC patient samples for LIV1, categorize the immune cell infiltration using CD4/CD8 expression and correlate the findings with therapy outcomes. Further, we also investigated for LIV1 expression in matched samples of primary & secondary tumors; pre & postchemotherapy in TNBC patients. Results showed an elevated expression of LIV1 in TNBC samples as compared to adjacent normal, the mean Q scores being 183.06 ± 6.39 and 120.78 ± 7.37 (p |
| doi_str_mv | 10.1002/jcp.31203 |
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Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zinc (Zn) transporter known to be overexpressed in few cancer types including BCs. Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN‐LIV1A for treatment of TNBC patients. Though LIV1 also has a role in modulating immune cells by its differential transport of Zn, a correlation between the tumor cell expression of LIV1 and immune cell infiltrations were scantily reported. Further adequate baseline data on LIV1 expression in other populations have not been documented. Our objective was to screen a large Indian cohort of TNBC patient samples for LIV1, categorize the immune cell infiltration using CD4/CD8 expression and correlate the findings with therapy outcomes. Further, we also investigated for LIV1 expression in matched samples of primary & secondary tumors; pre & postchemotherapy in TNBC patients. Results showed an elevated expression of LIV1 in TNBC samples as compared to adjacent normal, the mean Q scores being 183.06 ± 6.39 and 120.78 ± 7.37 (p < 0.0001), respectively. Similarly, LIV1 levels were elevated in secondary tumors than primary & in patient samples postchemotherapy as compared to naïve. In the TNBC cohort, using automated method, cell morphology parameters were computed and analysis showed LIV1 levels were elevated in grade 3 TNBC samples presenting with altered cell morphology parameters namely cell size, cell perimeter, & nucleus size. Thus indicating LIV1 expressing TNBC samples portrayed an aggressive phenotype. Finally, TNBC patients with 3+ staining intensity showed poor survival (4.44 year) as compared to patients with 2+ LIV1 expression (5.47 year), emphasizing that LIV1 expression is a poor prognostic factor in TNBC. In conclusion, the study reports elevated expression of LIV1 in a large Indian TNBC cohort; high expression is a poor prognostic factor and correlated with aggressive disease and indicating the need for LIV1 targeted therapies.]]></description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.31203</identifier><identifier>PMID: 38345361</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Antibodies ; Breast cancer ; Breast carcinoma ; CD4 antigen ; CD4/CD8 ; CD8 antigen ; Cell morphology ; Cell size ; Cell surface ; Correlation ; Cytology ; dIHC ; Estrogens ; Growth factors ; Immune system ; Infiltration ; LIV1 ; Medical prognosis ; Metastases ; Morphology ; Parameters ; Patients ; Phenotypes ; Progesterone ; QUPATH ; Receptors ; Therapeutic targets ; TILs ; TNBC ; Tumors ; Zinc ; Zinc transporter</subject><ispartof>Journal of cellular physiology, 2024-04, Vol.239 (4), p.e31203-n/a</ispartof><rights>2024 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3133-d3d96f402803fc338381db6d0d6eed0a7d7b1078802b7252f28f49e63a1d5cf53</cites><orcidid>0000-0003-0179-9785 ; 0000-0003-4394-4450</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.31203$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.31203$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38345361$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saravanan, Roshni</creatorcontrib><creatorcontrib>Balasubramanian, Vaishnavi</creatorcontrib><creatorcontrib>Sundaram, Sandhya</creatorcontrib><creatorcontrib>Dev, Bhawna</creatorcontrib><creatorcontrib>Vittalraj, Pavithra</creatorcontrib><creatorcontrib>Pitani, Ravi Shankar</creatorcontrib><creatorcontrib>Shanmugasundaram, Gouthaman</creatorcontrib><creatorcontrib>Rayala, Suresh Kumar</creatorcontrib><creatorcontrib>Venkatraman, Ganesh</creatorcontrib><title>Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description><![CDATA[Triple negative breast cancers (TNBC) are an aggressive molecular subtype of breast carcinoma (BC) identified by the lack of receptor expression for estrogen, progesterone, & human epidermal growth factor receptor‐2. Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zinc (Zn) transporter known to be overexpressed in few cancer types including BCs. Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN‐LIV1A for treatment of TNBC patients. Though LIV1 also has a role in modulating immune cells by its differential transport of Zn, a correlation between the tumor cell expression of LIV1 and immune cell infiltrations were scantily reported. Further adequate baseline data on LIV1 expression in other populations have not been documented. Our objective was to screen a large Indian cohort of TNBC patient samples for LIV1, categorize the immune cell infiltration using CD4/CD8 expression and correlate the findings with therapy outcomes. Further, we also investigated for LIV1 expression in matched samples of primary & secondary tumors; pre & postchemotherapy in TNBC patients. Results showed an elevated expression of LIV1 in TNBC samples as compared to adjacent normal, the mean Q scores being 183.06 ± 6.39 and 120.78 ± 7.37 (p < 0.0001), respectively. Similarly, LIV1 levels were elevated in secondary tumors than primary & in patient samples postchemotherapy as compared to naïve. In the TNBC cohort, using automated method, cell morphology parameters were computed and analysis showed LIV1 levels were elevated in grade 3 TNBC samples presenting with altered cell morphology parameters namely cell size, cell perimeter, & nucleus size. Thus indicating LIV1 expressing TNBC samples portrayed an aggressive phenotype. Finally, TNBC patients with 3+ staining intensity showed poor survival (4.44 year) as compared to patients with 2+ LIV1 expression (5.47 year), emphasizing that LIV1 expression is a poor prognostic factor in TNBC. In conclusion, the study reports elevated expression of LIV1 in a large Indian TNBC cohort; high expression is a poor prognostic factor and correlated with aggressive disease and indicating the need for LIV1 targeted therapies.]]></description><subject>Antibodies</subject><subject>Breast cancer</subject><subject>Breast carcinoma</subject><subject>CD4 antigen</subject><subject>CD4/CD8</subject><subject>CD8 antigen</subject><subject>Cell morphology</subject><subject>Cell size</subject><subject>Cell surface</subject><subject>Correlation</subject><subject>Cytology</subject><subject>dIHC</subject><subject>Estrogens</subject><subject>Growth factors</subject><subject>Immune system</subject><subject>Infiltration</subject><subject>LIV1</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Morphology</subject><subject>Parameters</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>Progesterone</subject><subject>QUPATH</subject><subject>Receptors</subject><subject>Therapeutic targets</subject><subject>TILs</subject><subject>TNBC</subject><subject>Tumors</subject><subject>Zinc</subject><subject>Zinc transporter</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp1kcFu1DAQhi1ERZfCgRdAlriUQ1rbkzjJEa0KFK0EB-BqOfa4eJW1g51AlxfgtfF2Sw9InH5p5tOnGf2EvODsgjMmLrdmugAuGDwiK876tqplIx6TVdnxqm9qfkqe5rxljPU9wBNyCh3UDUi-Ir-vbqeEOfsYaHTU4DjSvCSnDdJfPhg6Jx3yFNOMiW6uv3LqQ5n5aUQa8EbP_gfSIaHOMzU6mEL5THUomPVGzzEdtFMsOaV4E2K-W1s6f8Okpz112o9LwmfkxOkx4_P7PCNf3l59Xr-vNh_fXa_fbCoDHKCyYHvpaiY6Bs5A-aPjdpCWWYlomW5tO3DWdh0TQysa4UTn6h4laG4b4xo4I-dHb7nm-4J5VjufD1_rgHHJSvRCslZ2Qhb01T_oNi4plOsUMGgaBrzlhXp9pEyKOSd0akp-p9NecaYO7ajSjrprp7Av743LsEP7QP6towCXR-CnH3H_f5P6sP50VP4Be_KZmw</recordid><startdate>202404</startdate><enddate>202404</enddate><creator>Saravanan, Roshni</creator><creator>Balasubramanian, Vaishnavi</creator><creator>Sundaram, Sandhya</creator><creator>Dev, Bhawna</creator><creator>Vittalraj, Pavithra</creator><creator>Pitani, Ravi Shankar</creator><creator>Shanmugasundaram, Gouthaman</creator><creator>Rayala, Suresh Kumar</creator><creator>Venkatraman, Ganesh</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0179-9785</orcidid><orcidid>https://orcid.org/0000-0003-4394-4450</orcidid></search><sort><creationdate>202404</creationdate><title>Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure</title><author>Saravanan, Roshni ; Balasubramanian, Vaishnavi ; Sundaram, Sandhya ; Dev, Bhawna ; Vittalraj, Pavithra ; Pitani, Ravi Shankar ; Shanmugasundaram, Gouthaman ; Rayala, Suresh Kumar ; Venkatraman, Ganesh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3133-d3d96f402803fc338381db6d0d6eed0a7d7b1078802b7252f28f49e63a1d5cf53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antibodies</topic><topic>Breast cancer</topic><topic>Breast carcinoma</topic><topic>CD4 antigen</topic><topic>CD4/CD8</topic><topic>CD8 antigen</topic><topic>Cell morphology</topic><topic>Cell size</topic><topic>Cell surface</topic><topic>Correlation</topic><topic>Cytology</topic><topic>dIHC</topic><topic>Estrogens</topic><topic>Growth factors</topic><topic>Immune system</topic><topic>Infiltration</topic><topic>LIV1</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Morphology</topic><topic>Parameters</topic><topic>Patients</topic><topic>Phenotypes</topic><topic>Progesterone</topic><topic>QUPATH</topic><topic>Receptors</topic><topic>Therapeutic targets</topic><topic>TILs</topic><topic>TNBC</topic><topic>Tumors</topic><topic>Zinc</topic><topic>Zinc transporter</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saravanan, Roshni</creatorcontrib><creatorcontrib>Balasubramanian, Vaishnavi</creatorcontrib><creatorcontrib>Sundaram, Sandhya</creatorcontrib><creatorcontrib>Dev, Bhawna</creatorcontrib><creatorcontrib>Vittalraj, Pavithra</creatorcontrib><creatorcontrib>Pitani, Ravi Shankar</creatorcontrib><creatorcontrib>Shanmugasundaram, Gouthaman</creatorcontrib><creatorcontrib>Rayala, Suresh Kumar</creatorcontrib><creatorcontrib>Venkatraman, Ganesh</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saravanan, Roshni</au><au>Balasubramanian, Vaishnavi</au><au>Sundaram, Sandhya</au><au>Dev, Bhawna</au><au>Vittalraj, Pavithra</au><au>Pitani, Ravi Shankar</au><au>Shanmugasundaram, Gouthaman</au><au>Rayala, Suresh Kumar</au><au>Venkatraman, Ganesh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2024-04</date><risdate>2024</risdate><volume>239</volume><issue>4</issue><spage>e31203</spage><epage>n/a</epage><pages>e31203-n/a</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract><![CDATA[Triple negative breast cancers (TNBC) are an aggressive molecular subtype of breast carcinoma (BC) identified by the lack of receptor expression for estrogen, progesterone, & human epidermal growth factor receptor‐2. Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zinc (Zn) transporter known to be overexpressed in few cancer types including BCs. Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN‐LIV1A for treatment of TNBC patients. Though LIV1 also has a role in modulating immune cells by its differential transport of Zn, a correlation between the tumor cell expression of LIV1 and immune cell infiltrations were scantily reported. Further adequate baseline data on LIV1 expression in other populations have not been documented. Our objective was to screen a large Indian cohort of TNBC patient samples for LIV1, categorize the immune cell infiltration using CD4/CD8 expression and correlate the findings with therapy outcomes. Further, we also investigated for LIV1 expression in matched samples of primary & secondary tumors; pre & postchemotherapy in TNBC patients. Results showed an elevated expression of LIV1 in TNBC samples as compared to adjacent normal, the mean Q scores being 183.06 ± 6.39 and 120.78 ± 7.37 (p < 0.0001), respectively. Similarly, LIV1 levels were elevated in secondary tumors than primary & in patient samples postchemotherapy as compared to naïve. In the TNBC cohort, using automated method, cell morphology parameters were computed and analysis showed LIV1 levels were elevated in grade 3 TNBC samples presenting with altered cell morphology parameters namely cell size, cell perimeter, & nucleus size. Thus indicating LIV1 expressing TNBC samples portrayed an aggressive phenotype. Finally, TNBC patients with 3+ staining intensity showed poor survival (4.44 year) as compared to patients with 2+ LIV1 expression (5.47 year), emphasizing that LIV1 expression is a poor prognostic factor in TNBC. In conclusion, the study reports elevated expression of LIV1 in a large Indian TNBC cohort; high expression is a poor prognostic factor and correlated with aggressive disease and indicating the need for LIV1 targeted therapies.]]></abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38345361</pmid><doi>10.1002/jcp.31203</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-0179-9785</orcidid><orcidid>https://orcid.org/0000-0003-4394-4450</orcidid></addata></record> |
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| subjects | Antibodies Breast cancer Breast carcinoma CD4 antigen CD4/CD8 CD8 antigen Cell morphology Cell size Cell surface Correlation Cytology dIHC Estrogens Growth factors Immune system Infiltration LIV1 Medical prognosis Metastases Morphology Parameters Patients Phenotypes Progesterone QUPATH Receptors Therapeutic targets TILs TNBC Tumors Zinc Zinc transporter |
| title | Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure |
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