Decreased expression of autophagy protein LC3 and stemness (CD44+/CD24−/low) indicate poor prognosis in triple-negative breast cancer
Summary This study evaluated the prognostic value of expression of autophagy protein light chain 3 (LC3) and the prognostic value of coexpression of LC3 and stemness markers CD44+/CD24−/low in triple-negative breast cancer (TNBC). LC3 and LC3/CD44+/CD24−/low immunophenotypes in tumor tissues were ev...
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| Veröffentlicht in: | Human pathology 2016-02, Vol.48, p.48-55 |
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| creator | Chang, Shu-Jyuan, BS Ou-Yang, Fu, MD Tu, Hung-Pin, PhD Lin, Chih-Hung, MD Huang, Shu-Hung, MD Kostoro, Joanna, BS, MS Hou, Ming-Feng, MD Chai, Chee-Yin, MD, PhD Kwan, Aij-Lie, MD, PhD |
| description | Summary This study evaluated the prognostic value of expression of autophagy protein light chain 3 (LC3) and the prognostic value of coexpression of LC3 and stemness markers CD44+/CD24−/low in triple-negative breast cancer (TNBC). LC3 and LC3/CD44+/CD24−/low immunophenotypes in tumor tissues were evaluated by immunohistochemistry in 67 TNBC patients. LC3− was expressed in 30 (44.78%) cases. The LC3− phenotype revealed a significant negative association with overall survival in both univariate ( P = .0006) and multivariate ( P = .0153) analyses. LC3−/CD44+/CD24−/low phenotype was observed in 24 (35.82%) of 67 TNBC patients. According to Kaplan-Meier analysis, prognosis was significantly worse in tumors with LC3−/CD44+/CD24−/low phenotype ( P = .0280). Multivariate analysis indicated that LC3−/CD44+/CD24−/low phenotype was a significant independent prognostic indicator of overall survival. These results suggest that LC3 suppresses TNBC in mature tumor cells and cancer stem cells (CSCs). In conclusion, this study suggests that CSCs are linked to progression of autophagy in TNBC. During the progression and development of TNBC, autophagy of CSCs/progenitor cells is low. LC3−/CD44+/CD24−/low immunophenotype indicates a highly aggressive TNBC subgroup associated with a poor prognosis. This study investigated that LC3 deficiency may restrain TNBC in mature tumor cells and CSCs. Therefore, a reasonable inference is that inducing autophagy may be an effective therapeutic strategy in TNBC. |
| doi_str_mv | 10.1016/j.humpath.2015.09.034 |
| format | Article |
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LC3 and LC3/CD44+/CD24−/low immunophenotypes in tumor tissues were evaluated by immunohistochemistry in 67 TNBC patients. LC3− was expressed in 30 (44.78%) cases. The LC3− phenotype revealed a significant negative association with overall survival in both univariate ( P = .0006) and multivariate ( P = .0153) analyses. LC3−/CD44+/CD24−/low phenotype was observed in 24 (35.82%) of 67 TNBC patients. According to Kaplan-Meier analysis, prognosis was significantly worse in tumors with LC3−/CD44+/CD24−/low phenotype ( P = .0280). Multivariate analysis indicated that LC3−/CD44+/CD24−/low phenotype was a significant independent prognostic indicator of overall survival. These results suggest that LC3 suppresses TNBC in mature tumor cells and cancer stem cells (CSCs). In conclusion, this study suggests that CSCs are linked to progression of autophagy in TNBC. During the progression and development of TNBC, autophagy of CSCs/progenitor cells is low. LC3−/CD44+/CD24−/low immunophenotype indicates a highly aggressive TNBC subgroup associated with a poor prognosis. This study investigated that LC3 deficiency may restrain TNBC in mature tumor cells and CSCs. Therefore, a reasonable inference is that inducing autophagy may be an effective therapeutic strategy in TNBC.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2015.09.034</identifier><identifier>PMID: 26772398</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antigens ; Autophagy ; Autophagy - physiology ; Breast cancer ; Cancer stem cell ; Cancer therapies ; CD44+/CD24−/low ; Chemotherapy ; Confidence intervals ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Light chain 3 ; Medical prognosis ; Metastasis ; Microtubule-Associated Proteins - biosynthesis ; Middle Aged ; Mortality ; Neoplastic Stem Cells - pathology ; Pathology ; Phenotype ; Prognosis ; Proportional Hazards Models ; Proteins ; Studies ; Triple Negative Breast Neoplasms - metabolism ; Triple Negative Breast Neoplasms - mortality ; Triple Negative Breast Neoplasms - pathology ; Triple-negative breast cancer ; Tumors</subject><ispartof>Human pathology, 2016-02, Vol.48, p.48-55</ispartof><rights>Elsevier Inc.</rights><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Feb 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c363t-c661bf71a5edea200dfccea18105dc6ea946f18f2604a8f7aad5b6bd6fa5f4f23</citedby><cites>FETCH-LOGICAL-c363t-c661bf71a5edea200dfccea18105dc6ea946f18f2604a8f7aad5b6bd6fa5f4f23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.humpath.2015.09.034$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26772398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Shu-Jyuan, BS</creatorcontrib><creatorcontrib>Ou-Yang, Fu, MD</creatorcontrib><creatorcontrib>Tu, Hung-Pin, PhD</creatorcontrib><creatorcontrib>Lin, Chih-Hung, MD</creatorcontrib><creatorcontrib>Huang, Shu-Hung, MD</creatorcontrib><creatorcontrib>Kostoro, Joanna, BS, MS</creatorcontrib><creatorcontrib>Hou, Ming-Feng, MD</creatorcontrib><creatorcontrib>Chai, Chee-Yin, MD, PhD</creatorcontrib><creatorcontrib>Kwan, Aij-Lie, MD, PhD</creatorcontrib><title>Decreased expression of autophagy protein LC3 and stemness (CD44+/CD24−/low) indicate poor prognosis in triple-negative breast cancer</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Summary This study evaluated the prognostic value of expression of autophagy protein light chain 3 (LC3) and the prognostic value of coexpression of LC3 and stemness markers CD44+/CD24−/low in triple-negative breast cancer (TNBC). LC3 and LC3/CD44+/CD24−/low immunophenotypes in tumor tissues were evaluated by immunohistochemistry in 67 TNBC patients. LC3− was expressed in 30 (44.78%) cases. The LC3− phenotype revealed a significant negative association with overall survival in both univariate ( P = .0006) and multivariate ( P = .0153) analyses. LC3−/CD44+/CD24−/low phenotype was observed in 24 (35.82%) of 67 TNBC patients. According to Kaplan-Meier analysis, prognosis was significantly worse in tumors with LC3−/CD44+/CD24−/low phenotype ( P = .0280). Multivariate analysis indicated that LC3−/CD44+/CD24−/low phenotype was a significant independent prognostic indicator of overall survival. These results suggest that LC3 suppresses TNBC in mature tumor cells and cancer stem cells (CSCs). In conclusion, this study suggests that CSCs are linked to progression of autophagy in TNBC. During the progression and development of TNBC, autophagy of CSCs/progenitor cells is low. LC3−/CD44+/CD24−/low immunophenotype indicates a highly aggressive TNBC subgroup associated with a poor prognosis. This study investigated that LC3 deficiency may restrain TNBC in mature tumor cells and CSCs. Therefore, a reasonable inference is that inducing autophagy may be an effective therapeutic strategy in TNBC.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens</subject><subject>Autophagy</subject><subject>Autophagy - physiology</subject><subject>Breast cancer</subject><subject>Cancer stem cell</subject><subject>Cancer therapies</subject><subject>CD44+/CD24−/low</subject><subject>Chemotherapy</subject><subject>Confidence intervals</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Light chain 3</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Microtubule-Associated Proteins - biosynthesis</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Pathology</subject><subject>Phenotype</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Proteins</subject><subject>Studies</subject><subject>Triple Negative Breast Neoplasms - metabolism</subject><subject>Triple Negative Breast Neoplasms - mortality</subject><subject>Triple Negative Breast Neoplasms - pathology</subject><subject>Triple-negative breast cancer</subject><subject>Tumors</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksuO0zAUhiMEYsrAI4AssQGhpHZ8SbIBoZabVIkFsLYc-7h1aeOM7c5MnwDWPCJPgqMWkNiwsnT0X3w-naJ4THBFMBHzbbU57EeVNlWNCa9wV2HK7hQzwmldtrSr7xYzjJkoW9I0F8WDGLcYE8IZv19c1KJpatq1s-LbEnQAFcEguB0DxOj8gLxF6pD8uFHrIxqDT-AGtFpQpAaDYoL9kIXo2WLJ2Iv5Ylmzn99_zHf-5jlyg3FaJUCj92GyrgcfXcxzlIIbd1AOsFbJXQPqp96EtBo0hIfFPat2ER6d38viy9s3nxfvy9XHdx8Wr1elpoKmUgtBetsQxcGAqjE2VmtQpCWYGy1AdUxY0tpaYKZa2yhleC96I6ziltmaXhZPT7n5a1cHiElu_SEMuVKShouO0ablWcVPKh18jAGsHIPbq3CUBMsJv9zKM3454Ze4kxl_9j05px_6PZg_rt-8s-DVSQB5x2sHQUbtIAMwLoBO0nj334qX_yTonRsy891XOEL8u42MtcTy03QD0wkQjjHtGkZ_AeG1sJ0</recordid><startdate>20160201</startdate><enddate>20160201</enddate><creator>Chang, Shu-Jyuan, BS</creator><creator>Ou-Yang, Fu, MD</creator><creator>Tu, Hung-Pin, PhD</creator><creator>Lin, Chih-Hung, MD</creator><creator>Huang, Shu-Hung, MD</creator><creator>Kostoro, Joanna, BS, MS</creator><creator>Hou, Ming-Feng, MD</creator><creator>Chai, Chee-Yin, MD, PhD</creator><creator>Kwan, Aij-Lie, MD, PhD</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>K9.</scope></search><sort><creationdate>20160201</creationdate><title>Decreased expression of autophagy protein LC3 and stemness (CD44+/CD24−/low) indicate poor prognosis in triple-negative breast cancer</title><author>Chang, Shu-Jyuan, BS ; Ou-Yang, Fu, MD ; Tu, Hung-Pin, PhD ; Lin, Chih-Hung, MD ; Huang, Shu-Hung, MD ; Kostoro, Joanna, BS, MS ; Hou, Ming-Feng, MD ; Chai, Chee-Yin, MD, PhD ; Kwan, Aij-Lie, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c363t-c661bf71a5edea200dfccea18105dc6ea946f18f2604a8f7aad5b6bd6fa5f4f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antigens</topic><topic>Autophagy</topic><topic>Autophagy - physiology</topic><topic>Breast cancer</topic><topic>Cancer stem cell</topic><topic>Cancer therapies</topic><topic>CD44+/CD24−/low</topic><topic>Chemotherapy</topic><topic>Confidence intervals</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Light chain 3</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>Microtubule-Associated Proteins - biosynthesis</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Pathology</topic><topic>Phenotype</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Proteins</topic><topic>Studies</topic><topic>Triple Negative Breast Neoplasms - metabolism</topic><topic>Triple Negative Breast Neoplasms - mortality</topic><topic>Triple Negative Breast Neoplasms - pathology</topic><topic>Triple-negative breast cancer</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Shu-Jyuan, BS</creatorcontrib><creatorcontrib>Ou-Yang, Fu, MD</creatorcontrib><creatorcontrib>Tu, Hung-Pin, PhD</creatorcontrib><creatorcontrib>Lin, Chih-Hung, MD</creatorcontrib><creatorcontrib>Huang, Shu-Hung, MD</creatorcontrib><creatorcontrib>Kostoro, Joanna, BS, MS</creatorcontrib><creatorcontrib>Hou, Ming-Feng, MD</creatorcontrib><creatorcontrib>Chai, Chee-Yin, MD, PhD</creatorcontrib><creatorcontrib>Kwan, Aij-Lie, MD, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Shu-Jyuan, BS</au><au>Ou-Yang, Fu, MD</au><au>Tu, Hung-Pin, PhD</au><au>Lin, Chih-Hung, MD</au><au>Huang, Shu-Hung, MD</au><au>Kostoro, Joanna, BS, MS</au><au>Hou, Ming-Feng, MD</au><au>Chai, Chee-Yin, MD, PhD</au><au>Kwan, Aij-Lie, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased expression of autophagy protein LC3 and stemness (CD44+/CD24−/low) indicate poor prognosis in triple-negative breast cancer</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2016-02-01</date><risdate>2016</risdate><volume>48</volume><spage>48</spage><epage>55</epage><pages>48-55</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><abstract>Summary This study evaluated the prognostic value of expression of autophagy protein light chain 3 (LC3) and the prognostic value of coexpression of LC3 and stemness markers CD44+/CD24−/low in triple-negative breast cancer (TNBC). LC3 and LC3/CD44+/CD24−/low immunophenotypes in tumor tissues were evaluated by immunohistochemistry in 67 TNBC patients. LC3− was expressed in 30 (44.78%) cases. The LC3− phenotype revealed a significant negative association with overall survival in both univariate ( P = .0006) and multivariate ( P = .0153) analyses. LC3−/CD44+/CD24−/low phenotype was observed in 24 (35.82%) of 67 TNBC patients. According to Kaplan-Meier analysis, prognosis was significantly worse in tumors with LC3−/CD44+/CD24−/low phenotype ( P = .0280). Multivariate analysis indicated that LC3−/CD44+/CD24−/low phenotype was a significant independent prognostic indicator of overall survival. These results suggest that LC3 suppresses TNBC in mature tumor cells and cancer stem cells (CSCs). In conclusion, this study suggests that CSCs are linked to progression of autophagy in TNBC. During the progression and development of TNBC, autophagy of CSCs/progenitor cells is low. LC3−/CD44+/CD24−/low immunophenotype indicates a highly aggressive TNBC subgroup associated with a poor prognosis. This study investigated that LC3 deficiency may restrain TNBC in mature tumor cells and CSCs. Therefore, a reasonable inference is that inducing autophagy may be an effective therapeutic strategy in TNBC.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26772398</pmid><doi>10.1016/j.humpath.2015.09.034</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Antigens Autophagy Autophagy - physiology Breast cancer Cancer stem cell Cancer therapies CD44+/CD24−/low Chemotherapy Confidence intervals Female Humans Immunohistochemistry Kaplan-Meier Estimate Light chain 3 Medical prognosis Metastasis Microtubule-Associated Proteins - biosynthesis Middle Aged Mortality Neoplastic Stem Cells - pathology Pathology Phenotype Prognosis Proportional Hazards Models Proteins Studies Triple Negative Breast Neoplasms - metabolism Triple Negative Breast Neoplasms - mortality Triple Negative Breast Neoplasms - pathology Triple-negative breast cancer Tumors |
| title | Decreased expression of autophagy protein LC3 and stemness (CD44+/CD24−/low) indicate poor prognosis in triple-negative breast cancer |
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