Programmed death‐ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER 2‐negative status
Gastric cancer ( GC ) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death‐1 ( PD ‐1)/programmed death‐ligand 1 ( PD ‐L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exis...
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| creator | Wang, Lei Zhang, Qiongyan Ni, Shujuan Tan, Cong Cai, Xu Huang, Dan Sheng, Weiqi |
| description | Gastric cancer (
GC
) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death‐1 (
PD
‐1)/programmed death‐ligand 1 (
PD
‐L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exist concerning the expression status of
PD
‐L1 and its prognostic value in
GC
. We aimed to evaluate the expression rates of
PD
‐L1 in
GC
, and further assess its relationship with mismatch repair (
MMR
), and human epidermal growth factor receptor 2 (
HER
2) status. We retrospectively collected 550 consecutive cases of
GC
in Fudan University Shanghai Cancer Center from 2010 to 2012.
PD
‐L1,
MMR
protein, and
HER
2 status were detected by immunohistochemistry (
IHC
). Fluorescence in situ hybridization was further used in
HER
2
IHC
2+ cases. Cases with at least 1% membranous and/or cytoplasmic
PD
‐L1 staining in either tumor cells (
TC
s) or tumor‐infiltrating immune cells (
TIIC
s) were considered as
PD
‐L1 positive. The correlation between clinicopathological parameters,
HER
2,
MMR
, and
PD
‐L1 expression status was determined using chi‐squared tests. About 37.3% cases (205/550) showed
PD
‐L1 expression in
TC
s and/or
TIIC
s. 17.3% cases (95/550) showed
PD
‐L1 expression in
TC
s, 34.5% (190/550) cases showed
PD
‐L1 expression in
TIIC
s. There were 45 deficient
MMR
(
dMMR
) cases (8.2%), which showed higher rates of
PD
‐L1 expression compared with
MMR
‐proficient carcinomas (60.0% vs. 35.2%,
P
= 0.001).
HER
2 was positive in 66 (12.0%) cases. The expression of
PD
‐L1 occurred more frequently in
HER
2‐negative group than
HER
2‐positive cohorts (39.0% vs. 24.2%,
P
= 0.020). The survival analysis revealed that
PD
‐L1 was not associated with prognosis. This study evaluated the association between the
PD
‐L1 expression and a specific subgroup (
dMMR
and
HER
2‐negative) in a large Asian cohort of
GC
.
GC
patients with
dMMR
and
HER
2‐negative status exhibited higher
PD
‐L1 expression rates. Our finding indicated that
MMR
and
HER
‐2 status might be potential biomarkers for anti‐
PD
‐L1 therapy. |
| doi_str_mv | 10.1002/cam4.1502 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2057169059</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2057169059</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1029-7ddcb1db4666870c53c0ee704792cf3fec6d5174ea3a582a1820776e25a8def53</originalsourceid><addsrcrecordid>eNpNkE1OwzAQhS0EElXpghtYYsUixXZiO2GHqkKRKoEQrKOpM0ldNT_YLtAd3IAzchISlQWzmZHmzfdGj5BzzqacMXFloE6mXDJxREaCJTLSKk6O_82nZOL9hvWlmVCaj8jXo2srB3WNBS0Qwvrn83trK2gKyil-dA69t21DbUMr8MFZQw00Bt01Na1zuIUwrN9tWNPa-hqCWVOHHVjX80prLDZmTwfeYv5ERY9vsOqP3pD6AGHnz8hJCVuPk78-Ji-38-fZIlo-3N3PbpaR4UxkkS4Ks-LFKlFKpZoZGRuGqFmiM2HKuESjCsl1ghCDTAXwVDCtFQoJaf-IjMfk4sDtXPu6Qx_yTbtzTW-ZCyY1VxmTWa-6PKiMa713WOadszW4fc5ZPoScDyHnQ8jxL-R9ciY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2057169059</pqid></control><display><type>article</type><title>Programmed death‐ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER 2‐negative status</title><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Wiley Online Library Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Wang, Lei ; Zhang, Qiongyan ; Ni, Shujuan ; Tan, Cong ; Cai, Xu ; Huang, Dan ; Sheng, Weiqi</creator><creatorcontrib>Wang, Lei ; Zhang, Qiongyan ; Ni, Shujuan ; Tan, Cong ; Cai, Xu ; Huang, Dan ; Sheng, Weiqi</creatorcontrib><description>Gastric cancer (
GC
) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death‐1 (
PD
‐1)/programmed death‐ligand 1 (
PD
‐L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exist concerning the expression status of
PD
‐L1 and its prognostic value in
GC
. We aimed to evaluate the expression rates of
PD
‐L1 in
GC
, and further assess its relationship with mismatch repair (
MMR
), and human epidermal growth factor receptor 2 (
HER
2) status. We retrospectively collected 550 consecutive cases of
GC
in Fudan University Shanghai Cancer Center from 2010 to 2012.
PD
‐L1,
MMR
protein, and
HER
2 status were detected by immunohistochemistry (
IHC
). Fluorescence in situ hybridization was further used in
HER
2
IHC
2+ cases. Cases with at least 1% membranous and/or cytoplasmic
PD
‐L1 staining in either tumor cells (
TC
s) or tumor‐infiltrating immune cells (
TIIC
s) were considered as
PD
‐L1 positive. The correlation between clinicopathological parameters,
HER
2,
MMR
, and
PD
‐L1 expression status was determined using chi‐squared tests. About 37.3% cases (205/550) showed
PD
‐L1 expression in
TC
s and/or
TIIC
s. 17.3% cases (95/550) showed
PD
‐L1 expression in
TC
s, 34.5% (190/550) cases showed
PD
‐L1 expression in
TIIC
s. There were 45 deficient
MMR
(
dMMR
) cases (8.2%), which showed higher rates of
PD
‐L1 expression compared with
MMR
‐proficient carcinomas (60.0% vs. 35.2%,
P
= 0.001).
HER
2 was positive in 66 (12.0%) cases. The expression of
PD
‐L1 occurred more frequently in
HER
2‐negative group than
HER
2‐positive cohorts (39.0% vs. 24.2%,
P
= 0.020). The survival analysis revealed that
PD
‐L1 was not associated with prognosis. This study evaluated the association between the
PD
‐L1 expression and a specific subgroup (
dMMR
and
HER
2‐negative) in a large Asian cohort of
GC
.
GC
patients with
dMMR
and
HER
2‐negative status exhibited higher
PD
‐L1 expression rates. Our finding indicated that
MMR
and
HER
‐2 status might be potential biomarkers for anti‐
PD
‐L1 therapy.</description><identifier>ISSN: 2045-7634</identifier><identifier>EISSN: 2045-7634</identifier><identifier>DOI: 10.1002/cam4.1502</identifier><language>eng</language><publisher>Bognor Regis: John Wiley & Sons, Inc</publisher><subject>Apoptosis ; Carcinoma ; Death ; Epidermal growth factor ; ErbB-2 protein ; Fluorescence in situ hybridization ; Gastric cancer ; Immunohistochemistry ; Immunotherapy ; Ligands ; Medical prognosis ; Mismatch repair ; MMR protein ; PD-1 protein ; PD-L1 protein ; Survival analysis ; Tumor cells</subject><ispartof>Cancer medicine (Malden, MA), 2018-06, Vol.7 (6), p.2612-2620</ispartof><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1029-7ddcb1db4666870c53c0ee704792cf3fec6d5174ea3a582a1820776e25a8def53</citedby><cites>FETCH-LOGICAL-c1029-7ddcb1db4666870c53c0ee704792cf3fec6d5174ea3a582a1820776e25a8def53</cites><orcidid>0000-0001-9093-3418</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,861,27905,27906</link.rule.ids></links><search><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Zhang, Qiongyan</creatorcontrib><creatorcontrib>Ni, Shujuan</creatorcontrib><creatorcontrib>Tan, Cong</creatorcontrib><creatorcontrib>Cai, Xu</creatorcontrib><creatorcontrib>Huang, Dan</creatorcontrib><creatorcontrib>Sheng, Weiqi</creatorcontrib><title>Programmed death‐ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER 2‐negative status</title><title>Cancer medicine (Malden, MA)</title><description>Gastric cancer (
GC
) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death‐1 (
PD
‐1)/programmed death‐ligand 1 (
PD
‐L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exist concerning the expression status of
PD
‐L1 and its prognostic value in
GC
. We aimed to evaluate the expression rates of
PD
‐L1 in
GC
, and further assess its relationship with mismatch repair (
MMR
), and human epidermal growth factor receptor 2 (
HER
2) status. We retrospectively collected 550 consecutive cases of
GC
in Fudan University Shanghai Cancer Center from 2010 to 2012.
PD
‐L1,
MMR
protein, and
HER
2 status were detected by immunohistochemistry (
IHC
). Fluorescence in situ hybridization was further used in
HER
2
IHC
2+ cases. Cases with at least 1% membranous and/or cytoplasmic
PD
‐L1 staining in either tumor cells (
TC
s) or tumor‐infiltrating immune cells (
TIIC
s) were considered as
PD
‐L1 positive. The correlation between clinicopathological parameters,
HER
2,
MMR
, and
PD
‐L1 expression status was determined using chi‐squared tests. About 37.3% cases (205/550) showed
PD
‐L1 expression in
TC
s and/or
TIIC
s. 17.3% cases (95/550) showed
PD
‐L1 expression in
TC
s, 34.5% (190/550) cases showed
PD
‐L1 expression in
TIIC
s. There were 45 deficient
MMR
(
dMMR
) cases (8.2%), which showed higher rates of
PD
‐L1 expression compared with
MMR
‐proficient carcinomas (60.0% vs. 35.2%,
P
= 0.001).
HER
2 was positive in 66 (12.0%) cases. The expression of
PD
‐L1 occurred more frequently in
HER
2‐negative group than
HER
2‐positive cohorts (39.0% vs. 24.2%,
P
= 0.020). The survival analysis revealed that
PD
‐L1 was not associated with prognosis. This study evaluated the association between the
PD
‐L1 expression and a specific subgroup (
dMMR
and
HER
2‐negative) in a large Asian cohort of
GC
.
GC
patients with
dMMR
and
HER
2‐negative status exhibited higher
PD
‐L1 expression rates. Our finding indicated that
MMR
and
HER
‐2 status might be potential biomarkers for anti‐
PD
‐L1 therapy.</description><subject>Apoptosis</subject><subject>Carcinoma</subject><subject>Death</subject><subject>Epidermal growth factor</subject><subject>ErbB-2 protein</subject><subject>Fluorescence in situ hybridization</subject><subject>Gastric cancer</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>Ligands</subject><subject>Medical prognosis</subject><subject>Mismatch repair</subject><subject>MMR protein</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Survival analysis</subject><subject>Tumor cells</subject><issn>2045-7634</issn><issn>2045-7634</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpNkE1OwzAQhS0EElXpghtYYsUixXZiO2GHqkKRKoEQrKOpM0ldNT_YLtAd3IAzchISlQWzmZHmzfdGj5BzzqacMXFloE6mXDJxREaCJTLSKk6O_82nZOL9hvWlmVCaj8jXo2srB3WNBS0Qwvrn83trK2gKyil-dA69t21DbUMr8MFZQw00Bt01Na1zuIUwrN9tWNPa-hqCWVOHHVjX80prLDZmTwfeYv5ERY9vsOqP3pD6AGHnz8hJCVuPk78-Ji-38-fZIlo-3N3PbpaR4UxkkS4Ks-LFKlFKpZoZGRuGqFmiM2HKuESjCsl1ghCDTAXwVDCtFQoJaf-IjMfk4sDtXPu6Qx_yTbtzTW-ZCyY1VxmTWa-6PKiMa713WOadszW4fc5ZPoScDyHnQ8jxL-R9ciY</recordid><startdate>201806</startdate><enddate>201806</enddate><creator>Wang, Lei</creator><creator>Zhang, Qiongyan</creator><creator>Ni, Shujuan</creator><creator>Tan, Cong</creator><creator>Cai, Xu</creator><creator>Huang, Dan</creator><creator>Sheng, Weiqi</creator><general>John Wiley & Sons, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><orcidid>https://orcid.org/0000-0001-9093-3418</orcidid></search><sort><creationdate>201806</creationdate><title>Programmed death‐ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER 2‐negative status</title><author>Wang, Lei ; Zhang, Qiongyan ; Ni, Shujuan ; Tan, Cong ; Cai, Xu ; Huang, Dan ; Sheng, Weiqi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1029-7ddcb1db4666870c53c0ee704792cf3fec6d5174ea3a582a1820776e25a8def53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Apoptosis</topic><topic>Carcinoma</topic><topic>Death</topic><topic>Epidermal growth factor</topic><topic>ErbB-2 protein</topic><topic>Fluorescence in situ hybridization</topic><topic>Gastric cancer</topic><topic>Immunohistochemistry</topic><topic>Immunotherapy</topic><topic>Ligands</topic><topic>Medical prognosis</topic><topic>Mismatch repair</topic><topic>MMR protein</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Survival analysis</topic><topic>Tumor cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Zhang, Qiongyan</creatorcontrib><creatorcontrib>Ni, Shujuan</creatorcontrib><creatorcontrib>Tan, Cong</creatorcontrib><creatorcontrib>Cai, Xu</creatorcontrib><creatorcontrib>Huang, Dan</creatorcontrib><creatorcontrib>Sheng, Weiqi</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Cancer medicine (Malden, MA)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Lei</au><au>Zhang, Qiongyan</au><au>Ni, Shujuan</au><au>Tan, Cong</au><au>Cai, Xu</au><au>Huang, Dan</au><au>Sheng, Weiqi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Programmed death‐ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER 2‐negative status</atitle><jtitle>Cancer medicine (Malden, MA)</jtitle><date>2018-06</date><risdate>2018</risdate><volume>7</volume><issue>6</issue><spage>2612</spage><epage>2620</epage><pages>2612-2620</pages><issn>2045-7634</issn><eissn>2045-7634</eissn><abstract>Gastric cancer (
GC
) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death‐1 (
PD
‐1)/programmed death‐ligand 1 (
PD
‐L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exist concerning the expression status of
PD
‐L1 and its prognostic value in
GC
. We aimed to evaluate the expression rates of
PD
‐L1 in
GC
, and further assess its relationship with mismatch repair (
MMR
), and human epidermal growth factor receptor 2 (
HER
2) status. We retrospectively collected 550 consecutive cases of
GC
in Fudan University Shanghai Cancer Center from 2010 to 2012.
PD
‐L1,
MMR
protein, and
HER
2 status were detected by immunohistochemistry (
IHC
). Fluorescence in situ hybridization was further used in
HER
2
IHC
2+ cases. Cases with at least 1% membranous and/or cytoplasmic
PD
‐L1 staining in either tumor cells (
TC
s) or tumor‐infiltrating immune cells (
TIIC
s) were considered as
PD
‐L1 positive. The correlation between clinicopathological parameters,
HER
2,
MMR
, and
PD
‐L1 expression status was determined using chi‐squared tests. About 37.3% cases (205/550) showed
PD
‐L1 expression in
TC
s and/or
TIIC
s. 17.3% cases (95/550) showed
PD
‐L1 expression in
TC
s, 34.5% (190/550) cases showed
PD
‐L1 expression in
TIIC
s. There were 45 deficient
MMR
(
dMMR
) cases (8.2%), which showed higher rates of
PD
‐L1 expression compared with
MMR
‐proficient carcinomas (60.0% vs. 35.2%,
P
= 0.001).
HER
2 was positive in 66 (12.0%) cases. The expression of
PD
‐L1 occurred more frequently in
HER
2‐negative group than
HER
2‐positive cohorts (39.0% vs. 24.2%,
P
= 0.020). The survival analysis revealed that
PD
‐L1 was not associated with prognosis. This study evaluated the association between the
PD
‐L1 expression and a specific subgroup (
dMMR
and
HER
2‐negative) in a large Asian cohort of
GC
.
GC
patients with
dMMR
and
HER
2‐negative status exhibited higher
PD
‐L1 expression rates. Our finding indicated that
MMR
and
HER
‐2 status might be potential biomarkers for anti‐
PD
‐L1 therapy.</abstract><cop>Bognor Regis</cop><pub>John Wiley & Sons, Inc</pub><doi>10.1002/cam4.1502</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9093-3418</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-7634 |
| ispartof | Cancer medicine (Malden, MA), 2018-06, Vol.7 (6), p.2612-2620 |
| issn | 2045-7634 2045-7634 |
| language | eng |
| recordid | cdi_proquest_journals_2057169059 |
| source | DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; Wiley Online Library Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Apoptosis Carcinoma Death Epidermal growth factor ErbB-2 protein Fluorescence in situ hybridization Gastric cancer Immunohistochemistry Immunotherapy Ligands Medical prognosis Mismatch repair MMR protein PD-1 protein PD-L1 protein Survival analysis Tumor cells |
| title | Programmed death‐ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER 2‐negative status |
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