Wnt signaling pathway pharmacogenetics in non-small cell lung cancer
Wingless-type protein (Wnt)/β-catenin pathway alterations in non-small cell lung cancer (NSCLC) are associated with poor prognosis and resistance. In 598 stage III–IV NSCLC patients receiving platinum-based chemotherapy at the MD Anderson Cancer Center (MDACC), we correlated survival with 441 host s...
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| Veröffentlicht in: | The pharmacogenomics journal 2014-12, Vol.14 (6), p.509-522 |
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| creator | Stewart, D J Chang, D W Ye, Y Spitz, M Lu, C Shu, X Wampfler, J A Marks, R S Garces, Y I Yang, P Wu, X |
| description | Wingless-type protein (Wnt)/β-catenin pathway alterations in non-small cell lung cancer (NSCLC) are associated with poor prognosis and resistance. In 598 stage III–IV NSCLC patients receiving platinum-based chemotherapy at the MD Anderson Cancer Center (MDACC), we correlated survival with 441 host single-nucleotide polymorphisms (SNPs) in 50 Wnt pathway genes. We then assessed the most significant SNPs in 240 Mayo Clinic patients receiving platinum-based chemotherapy for advanced NSCLC, 127 MDACC patients receiving platinum-based adjuvant chemotherapy and 340 early stage MDACC patients undergoing surgery alone (cohorts 2–4). In multivariate analysis, survival correlates with SNPs for
AXIN2
(rs11868547 and rs4541111, of which rs11868547 was assessed in cohorts 2–4),
Wnt-5B
(rs12819505),
CXXC4
(rs4413407) and
WIF-1
(rs10878232). Median survival was 19.7, 15.6 and 10.7 months for patients with 1, 2 and 3–5 unfavorable genotypes, respectively (
P
=3.8 × 10
−9
). Survival tree analysis classified patients into two groups (median survival time 11.3 vs 17.3 months,
P
=4.7 × 10
−8
). None of the SNPs achieved significance in cohorts 2–4; however, there was a trend in the same direction as cohort 1 for 3 of the SNPs. Using online databases, we found rs10878232 displayed expression quantitative trait loci correlation with the expression of
LEMD3,
a neighboring gene previously associated with NSCLC survival. In conclusion, results from cohort 1 provide further evidence for an important role for Wnt in NSCLC. Investigation of Wnt inhibitors in advanced NSCLC would be reasonable. Lack of an SNP association with outcome in cohorts 2–4 could be due to low statistical power, impact of patient heterogeneity or false-positive observations in cohort 1. |
| doi_str_mv | 10.1038/tpj.2014.21 |
| format | Article |
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AXIN2
(rs11868547 and rs4541111, of which rs11868547 was assessed in cohorts 2–4),
Wnt-5B
(rs12819505),
CXXC4
(rs4413407) and
WIF-1
(rs10878232). Median survival was 19.7, 15.6 and 10.7 months for patients with 1, 2 and 3–5 unfavorable genotypes, respectively (
P
=3.8 × 10
−9
). Survival tree analysis classified patients into two groups (median survival time 11.3 vs 17.3 months,
P
=4.7 × 10
−8
). None of the SNPs achieved significance in cohorts 2–4; however, there was a trend in the same direction as cohort 1 for 3 of the SNPs. Using online databases, we found rs10878232 displayed expression quantitative trait loci correlation with the expression of
LEMD3,
a neighboring gene previously associated with NSCLC survival. In conclusion, results from cohort 1 provide further evidence for an important role for Wnt in NSCLC. Investigation of Wnt inhibitors in advanced NSCLC would be reasonable. Lack of an SNP association with outcome in cohorts 2–4 could be due to low statistical power, impact of patient heterogeneity or false-positive observations in cohort 1.</description><identifier>ISSN: 1470-269X</identifier><identifier>EISSN: 1473-1150</identifier><identifier>DOI: 10.1038/tpj.2014.21</identifier><identifier>PMID: 24980784</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 45/43 ; 692/499 ; Adult ; Aged ; Aged, 80 and over ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Carcinoma, Non-Small-Cell Lung - diagnosis ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Chemotherapy ; Cohort Studies ; Drug metabolism ; Female ; Gene Expression ; Genetic aspects ; Human Genetics ; Humans ; Identification and classification ; Lung cancer ; Lung cancer, Non-small cell ; Lung Neoplasms - diagnosis ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Male ; Medical prognosis ; Middle Aged ; Multivariate Analysis ; Non-small cell lung carcinoma ; Oncology ; original-article ; Patient outcomes ; Patients ; Pharmacogenetics ; Pharmacotherapy ; Platinum ; Psychopharmacology ; Quantitative trait loci ; Signal transduction ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Small cell lung carcinoma ; Wnt protein ; Wnt Proteins - antagonists & inhibitors ; Wnt Proteins - metabolism ; Wnt Signaling Pathway - drug effects ; Wnt Signaling Pathway - genetics ; β-Catenin</subject><ispartof>The pharmacogenomics journal, 2014-12, Vol.14 (6), p.509-522</ispartof><rights>Macmillan Publishers Limited 2014</rights><rights>COPYRIGHT 2014 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 2014</rights><rights>Macmillan Publishers Limited 2014.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c605t-ae04ee2ed4d63dc5d57ffaf6ca82b92163e583e56a271d562a960dd64f2fb3cd3</citedby><cites>FETCH-LOGICAL-c605t-ae04ee2ed4d63dc5d57ffaf6ca82b92163e583e56a271d562a960dd64f2fb3cd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24980784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stewart, D J</creatorcontrib><creatorcontrib>Chang, D W</creatorcontrib><creatorcontrib>Ye, Y</creatorcontrib><creatorcontrib>Spitz, M</creatorcontrib><creatorcontrib>Lu, C</creatorcontrib><creatorcontrib>Shu, X</creatorcontrib><creatorcontrib>Wampfler, J A</creatorcontrib><creatorcontrib>Marks, R S</creatorcontrib><creatorcontrib>Garces, Y I</creatorcontrib><creatorcontrib>Yang, P</creatorcontrib><creatorcontrib>Wu, X</creatorcontrib><title>Wnt signaling pathway pharmacogenetics in non-small cell lung cancer</title><title>The pharmacogenomics journal</title><addtitle>Pharmacogenomics J</addtitle><addtitle>Pharmacogenomics J</addtitle><description>Wingless-type protein (Wnt)/β-catenin pathway alterations in non-small cell lung cancer (NSCLC) are associated with poor prognosis and resistance. In 598 stage III–IV NSCLC patients receiving platinum-based chemotherapy at the MD Anderson Cancer Center (MDACC), we correlated survival with 441 host single-nucleotide polymorphisms (SNPs) in 50 Wnt pathway genes. We then assessed the most significant SNPs in 240 Mayo Clinic patients receiving platinum-based chemotherapy for advanced NSCLC, 127 MDACC patients receiving platinum-based adjuvant chemotherapy and 340 early stage MDACC patients undergoing surgery alone (cohorts 2–4). In multivariate analysis, survival correlates with SNPs for
AXIN2
(rs11868547 and rs4541111, of which rs11868547 was assessed in cohorts 2–4),
Wnt-5B
(rs12819505),
CXXC4
(rs4413407) and
WIF-1
(rs10878232). Median survival was 19.7, 15.6 and 10.7 months for patients with 1, 2 and 3–5 unfavorable genotypes, respectively (
P
=3.8 × 10
−9
). Survival tree analysis classified patients into two groups (median survival time 11.3 vs 17.3 months,
P
=4.7 × 10
−8
). None of the SNPs achieved significance in cohorts 2–4; however, there was a trend in the same direction as cohort 1 for 3 of the SNPs. Using online databases, we found rs10878232 displayed expression quantitative trait loci correlation with the expression of
LEMD3,
a neighboring gene previously associated with NSCLC survival. In conclusion, results from cohort 1 provide further evidence for an important role for Wnt in NSCLC. Investigation of Wnt inhibitors in advanced NSCLC would be reasonable. Lack of an SNP association with outcome in cohorts 2–4 could be due to low statistical power, impact of patient heterogeneity or false-positive observations in cohort 1.</description><subject>45</subject><subject>45/43</subject><subject>692/499</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Carcinoma, Non-Small-Cell Lung - diagnosis</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Chemotherapy</subject><subject>Cohort Studies</subject><subject>Drug metabolism</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Genetic aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Lung cancer</subject><subject>Lung cancer, Non-small cell</subject><subject>Lung Neoplasms - diagnosis</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Non-small cell lung carcinoma</subject><subject>Oncology</subject><subject>original-article</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Pharmacogenetics</subject><subject>Pharmacotherapy</subject><subject>Platinum</subject><subject>Psychopharmacology</subject><subject>Quantitative trait loci</subject><subject>Signal transduction</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Small cell lung carcinoma</subject><subject>Wnt protein</subject><subject>Wnt Proteins - antagonists & inhibitors</subject><subject>Wnt Proteins - metabolism</subject><subject>Wnt Signaling Pathway - drug effects</subject><subject>Wnt Signaling Pathway - genetics</subject><subject>β-Catenin</subject><issn>1470-269X</issn><issn>1473-1150</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNksuL1TAUxoMoznh15V4KbgTtNa8m6UYYxicMuFF0F85N0t5c2qQmrTL_val3HEcRcZEHnB_fyfnyIfSQ4C3BTD2fp8OWYsK3lNxCp4RLVhPS4Ns_7rimov18gu7lfMCYCCLVXXRCeauwVPwUvfwU5ir7PsDgQ19NMO-_wWU17SGNYGLvgpu9yZUPVYihziMMQ2Vc2Yal8AaCcek-utPBkN2Dq3ODPr5-9eH8bX3x_s2787OL2gjczDU4zJ2jznIrmDWNbWTXQScMKLprKRHMNaosAVQS2wgKrcDWCt7RbseMZRv04qg7LbvRWePCnGDQU_IjpEsdwevfK8HvdR-_ak6ZFEV_g55cCaT4ZXF51qPP6zQQXFyyJkJwiqli9D9QKrHkRDUFffwHeohLKo5mTQUnEitB2n9RRatpsSq_9ovqYXDahy6WQczaWp-x4pEUQq7U0yNlUsw5ue7aA4L1GgpdQqHXUGhKCv3opm3X7M8UFODZEcilFHqXbjztL3rfARkKv9Q</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Stewart, D J</creator><creator>Chang, D W</creator><creator>Ye, Y</creator><creator>Spitz, M</creator><creator>Lu, C</creator><creator>Shu, X</creator><creator>Wampfler, J A</creator><creator>Marks, R S</creator><creator>Garces, Y I</creator><creator>Yang, P</creator><creator>Wu, X</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20141201</creationdate><title>Wnt signaling pathway pharmacogenetics in non-small cell lung cancer</title><author>Stewart, D J ; Chang, D W ; Ye, Y ; Spitz, M ; Lu, C ; Shu, X ; Wampfler, J A ; Marks, R S ; Garces, Y I ; Yang, P ; Wu, X</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c605t-ae04ee2ed4d63dc5d57ffaf6ca82b92163e583e56a271d562a960dd64f2fb3cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>45</topic><topic>45/43</topic><topic>692/499</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Carcinoma, Non-Small-Cell Lung - diagnosis</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Chemotherapy</topic><topic>Cohort Studies</topic><topic>Drug metabolism</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Genetic aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Lung cancer</topic><topic>Lung cancer, Non-small cell</topic><topic>Lung Neoplasms - diagnosis</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Non-small cell lung carcinoma</topic><topic>Oncology</topic><topic>original-article</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Pharmacogenetics</topic><topic>Pharmacotherapy</topic><topic>Platinum</topic><topic>Psychopharmacology</topic><topic>Quantitative trait loci</topic><topic>Signal transduction</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Small cell lung carcinoma</topic><topic>Wnt protein</topic><topic>Wnt Proteins - antagonists & inhibitors</topic><topic>Wnt Proteins - metabolism</topic><topic>Wnt Signaling Pathway - drug effects</topic><topic>Wnt Signaling Pathway - genetics</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stewart, D J</creatorcontrib><creatorcontrib>Chang, D W</creatorcontrib><creatorcontrib>Ye, Y</creatorcontrib><creatorcontrib>Spitz, M</creatorcontrib><creatorcontrib>Lu, C</creatorcontrib><creatorcontrib>Shu, X</creatorcontrib><creatorcontrib>Wampfler, J A</creatorcontrib><creatorcontrib>Marks, R S</creatorcontrib><creatorcontrib>Garces, Y I</creatorcontrib><creatorcontrib>Yang, P</creatorcontrib><creatorcontrib>Wu, X</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 Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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>Engineering Research Database</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>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The pharmacogenomics journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stewart, D J</au><au>Chang, D W</au><au>Ye, Y</au><au>Spitz, M</au><au>Lu, C</au><au>Shu, X</au><au>Wampfler, J A</au><au>Marks, R S</au><au>Garces, Y I</au><au>Yang, P</au><au>Wu, X</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wnt signaling pathway pharmacogenetics in non-small cell lung cancer</atitle><jtitle>The pharmacogenomics journal</jtitle><stitle>Pharmacogenomics J</stitle><addtitle>Pharmacogenomics J</addtitle><date>2014-12-01</date><risdate>2014</risdate><volume>14</volume><issue>6</issue><spage>509</spage><epage>522</epage><pages>509-522</pages><issn>1470-269X</issn><eissn>1473-1150</eissn><abstract>Wingless-type protein (Wnt)/β-catenin pathway alterations in non-small cell lung cancer (NSCLC) are associated with poor prognosis and resistance. In 598 stage III–IV NSCLC patients receiving platinum-based chemotherapy at the MD Anderson Cancer Center (MDACC), we correlated survival with 441 host single-nucleotide polymorphisms (SNPs) in 50 Wnt pathway genes. We then assessed the most significant SNPs in 240 Mayo Clinic patients receiving platinum-based chemotherapy for advanced NSCLC, 127 MDACC patients receiving platinum-based adjuvant chemotherapy and 340 early stage MDACC patients undergoing surgery alone (cohorts 2–4). In multivariate analysis, survival correlates with SNPs for
AXIN2
(rs11868547 and rs4541111, of which rs11868547 was assessed in cohorts 2–4),
Wnt-5B
(rs12819505),
CXXC4
(rs4413407) and
WIF-1
(rs10878232). Median survival was 19.7, 15.6 and 10.7 months for patients with 1, 2 and 3–5 unfavorable genotypes, respectively (
P
=3.8 × 10
−9
). Survival tree analysis classified patients into two groups (median survival time 11.3 vs 17.3 months,
P
=4.7 × 10
−8
). None of the SNPs achieved significance in cohorts 2–4; however, there was a trend in the same direction as cohort 1 for 3 of the SNPs. Using online databases, we found rs10878232 displayed expression quantitative trait loci correlation with the expression of
LEMD3,
a neighboring gene previously associated with NSCLC survival. In conclusion, results from cohort 1 provide further evidence for an important role for Wnt in NSCLC. Investigation of Wnt inhibitors in advanced NSCLC would be reasonable. Lack of an SNP association with outcome in cohorts 2–4 could be due to low statistical power, impact of patient heterogeneity or false-positive observations in cohort 1.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24980784</pmid><doi>10.1038/tpj.2014.21</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The pharmacogenomics journal, 2014-12, Vol.14 (6), p.509-522 |
| issn | 1470-269X 1473-1150 |
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| subjects | 45 45/43 692/499 Adult Aged Aged, 80 and over Biomedical and Life Sciences Biomedicine Cancer Carcinoma, Non-Small-Cell Lung - diagnosis Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Chemotherapy Cohort Studies Drug metabolism Female Gene Expression Genetic aspects Human Genetics Humans Identification and classification Lung cancer Lung cancer, Non-small cell Lung Neoplasms - diagnosis Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - metabolism Male Medical prognosis Middle Aged Multivariate Analysis Non-small cell lung carcinoma Oncology original-article Patient outcomes Patients Pharmacogenetics Pharmacotherapy Platinum Psychopharmacology Quantitative trait loci Signal transduction Single nucleotide polymorphisms Single-nucleotide polymorphism Small cell lung carcinoma Wnt protein Wnt Proteins - antagonists & inhibitors Wnt Proteins - metabolism Wnt Signaling Pathway - drug effects Wnt Signaling Pathway - genetics β-Catenin |
| title | Wnt signaling pathway pharmacogenetics in non-small cell lung cancer |
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