PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer
Background: Tumour cells exclusively express the embryonic M2 isoform of pyruvate kinase (PKM2). PKM2 expression levels have been correlated with the effect of platinum compounds in cancer cell lines and xenograft models. The potential predictive role of PKM2 in patients with metastatic/advanced non...
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| Veröffentlicht in: | British journal of cancer 2014-10, Vol.111 (9), p.1757-1764 |
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| creator | Papadaki, C Sfakianaki, M Lagoudaki, E Giagkas, G Ioannidis, G Trypaki, M Tsakalaki, E Voutsina, A Koutsopoulos, A Mavroudis, D Georgoulias, V Souglakos, J |
| description | Background:
Tumour cells exclusively express the embryonic M2 isoform of pyruvate kinase (PKM2). PKM2 expression levels have been correlated with the effect of platinum compounds in cancer cell lines and xenograft models. The potential predictive role of PKM2 in patients with metastatic/advanced non-small-cell lung cancer (NSCLC) receiving platinum-based chemotherapy as first-line was investigated.
Methods:
Quantitative real-time PCR was used to assess the expression of
PKM2
in tumour samples from 148 and 157 NSCLC patients in the training and the validation set, respectively. All patients received front-line platinum-based chemotherapy.
PKM2
mRNA expression was also analysed in a control group of 85 NSCLC patients treated with non-platinum containing regimens.
Results:
In the training set, high
PKM2
mRNA levels were associated with decreased progression-free survival (PFS; 4.9 months
vs
6.4,
P
=0.006), overall survival (OS; 10.1
vs
17.0 months,
P
=0.01) and disease control rate (DCR; 57.7%
vs
74.3%;
P
=0.021) compared to patients with low
PKM2
levels. In the validation set, high
PKM2
mRNA levels were also associated with deceased PFS (3.7
vs
5.9 months,
P
=0.006), OS (8.3
vs
16.8 months,
P
=0.003) and DCR (57.7%
vs
70.9%;
P
=0.049) compared to those with low
PKM2
mRNA levels. There was no correlation between the
PKM2
mRNA levels and the PFS (5.6
vs
5.9,
P
=0.43) or the OS (9.8
vs
10.1,
P=
0.51) in the control group. Multivariate analysis revealed high
PKM2
mRNA expression as an independent predictive factor for the poor patients’ outcome.
Conclusions:
PKM2
expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy. |
| doi_str_mv | 10.1038/bjc.2014.492 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4453739</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3474033761</sourcerecordid><originalsourceid>FETCH-LOGICAL-c480t-72c04fcd477292816cc0248b39aed7feb2fcb5fcc13075903cbd0fe49497d7af3</originalsourceid><addsrcrecordid>eNptkUuPFCEUhYnROO3ozrUhMe6k5VVNsTGZTHzFMbrQNaEo6KaloARqTP8E_7VMuh3HxBWB8-XcczkAPCV4TTDrXw17s6aY8DWX9B5YkY5RRHoq7oMVxlggLCk-A49K2berxL14CM5oRxljUqzAry8fP1GoC9Rw8GnS-bvN0KUMzc5OqdhYfPXXvh5gTdDlFCsKPlo4B119XCY06GLHI113Nuv5AH2Ec1NtrAX-9HUHJ1t1qe3JwJgiKpMOARkbAgxL3EKjo7H5MXjgdCj2yek8B9_evvl6-R5dfX734fLiChne44oENZg7M3IhqKQ92RiDKe8HJrUdhbMDdWbonDGEYdFJzMwwYme55FKMQjt2Dl4ffedlmOxoWsysg5qzb9sfVNJe_atEv1PbdK0475hgshk8Pxnk9GOxpap9WnJsmRXZENFjspGkUS-PlMmplGzd7QSC1U1xqhWnbopTrbiGP7ub6hb-01QDXpwAXYwOLrdP8-Uv18sNpZw1Dh250qS4tflOuv8N_g0zGrOn</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1617801691</pqid></control><display><type>article</type><title>PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer</title><source>MEDLINE</source><source>PubMed Central（OA）</source><source>Nature</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Papadaki, C ; Sfakianaki, M ; Lagoudaki, E ; Giagkas, G ; Ioannidis, G ; Trypaki, M ; Tsakalaki, E ; Voutsina, A ; Koutsopoulos, A ; Mavroudis, D ; Georgoulias, V ; Souglakos, J</creator><creatorcontrib>Papadaki, C ; Sfakianaki, M ; Lagoudaki, E ; Giagkas, G ; Ioannidis, G ; Trypaki, M ; Tsakalaki, E ; Voutsina, A ; Koutsopoulos, A ; Mavroudis, D ; Georgoulias, V ; Souglakos, J</creatorcontrib><description>Background:
Tumour cells exclusively express the embryonic M2 isoform of pyruvate kinase (PKM2). PKM2 expression levels have been correlated with the effect of platinum compounds in cancer cell lines and xenograft models. The potential predictive role of PKM2 in patients with metastatic/advanced non-small-cell lung cancer (NSCLC) receiving platinum-based chemotherapy as first-line was investigated.
Methods:
Quantitative real-time PCR was used to assess the expression of
PKM2
in tumour samples from 148 and 157 NSCLC patients in the training and the validation set, respectively. All patients received front-line platinum-based chemotherapy.
PKM2
mRNA expression was also analysed in a control group of 85 NSCLC patients treated with non-platinum containing regimens.
Results:
In the training set, high
PKM2
mRNA levels were associated with decreased progression-free survival (PFS; 4.9 months
vs
6.4,
P
=0.006), overall survival (OS; 10.1
vs
17.0 months,
P
=0.01) and disease control rate (DCR; 57.7%
vs
74.3%;
P
=0.021) compared to patients with low
PKM2
levels. In the validation set, high
PKM2
mRNA levels were also associated with deceased PFS (3.7
vs
5.9 months,
P
=0.006), OS (8.3
vs
16.8 months,
P
=0.003) and DCR (57.7%
vs
70.9%;
P
=0.049) compared to those with low
PKM2
mRNA levels. There was no correlation between the
PKM2
mRNA levels and the PFS (5.6
vs
5.9,
P
=0.43) or the OS (9.8
vs
10.1,
P=
0.51) in the control group. Multivariate analysis revealed high
PKM2
mRNA expression as an independent predictive factor for the poor patients’ outcome.
Conclusions:
PKM2
expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2014.492</identifier><identifier>PMID: 25233397</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject><![CDATA[692/53/2423 ; 692/699/67/1059/99 ; 692/699/67/1612/1350 ; 692/699/67/322 ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bevacizumab ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - mortality ; Carcinoma, Non-Small-Cell Lung - secondary ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - secondary ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Deoxycytidine - administration & dosage ; Deoxycytidine - analogs & derivatives ; Docetaxel ; Drug Resistance ; Epidemiology ; Female ; Follow-Up Studies ; Gemcitabine ; Glutamates - administration & dosage ; Guanine - administration & dosage ; Guanine - analogs & derivatives ; Humans ; Immunoenzyme Techniques ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - metabolism ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Lymphatic Metastasis ; Male ; Medical sciences ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Middle Aged ; Molecular Medicine ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Neoplasm Staging ; Oncology ; Pemetrexed ; Platinum - administration & dosage ; Pneumology ; Prognosis ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Survival Rate ; Taxoids - administration & dosage ; Thyroid Hormone-Binding Proteins ; Thyroid Hormones - genetics ; Thyroid Hormones - metabolism ; Translational Therapeutics ; Tumors ; Tumors of the respiratory system and mediastinum]]></subject><ispartof>British journal of cancer, 2014-10, Vol.111 (9), p.1757-1764</ispartof><rights>The Author(s) 2014</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Oct 28, 2014</rights><rights>Copyright © 2014 Cancer Research UK 2014 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-72c04fcd477292816cc0248b39aed7feb2fcb5fcc13075903cbd0fe49497d7af3</citedby><cites>FETCH-LOGICAL-c480t-72c04fcd477292816cc0248b39aed7feb2fcb5fcc13075903cbd0fe49497d7af3</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/PMC4453739/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453739/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28962243$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25233397$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Papadaki, C</creatorcontrib><creatorcontrib>Sfakianaki, M</creatorcontrib><creatorcontrib>Lagoudaki, E</creatorcontrib><creatorcontrib>Giagkas, G</creatorcontrib><creatorcontrib>Ioannidis, G</creatorcontrib><creatorcontrib>Trypaki, M</creatorcontrib><creatorcontrib>Tsakalaki, E</creatorcontrib><creatorcontrib>Voutsina, A</creatorcontrib><creatorcontrib>Koutsopoulos, A</creatorcontrib><creatorcontrib>Mavroudis, D</creatorcontrib><creatorcontrib>Georgoulias, V</creatorcontrib><creatorcontrib>Souglakos, J</creatorcontrib><title>PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
Tumour cells exclusively express the embryonic M2 isoform of pyruvate kinase (PKM2). PKM2 expression levels have been correlated with the effect of platinum compounds in cancer cell lines and xenograft models. The potential predictive role of PKM2 in patients with metastatic/advanced non-small-cell lung cancer (NSCLC) receiving platinum-based chemotherapy as first-line was investigated.
Methods:
Quantitative real-time PCR was used to assess the expression of
PKM2
in tumour samples from 148 and 157 NSCLC patients in the training and the validation set, respectively. All patients received front-line platinum-based chemotherapy.
PKM2
mRNA expression was also analysed in a control group of 85 NSCLC patients treated with non-platinum containing regimens.
Results:
In the training set, high
PKM2
mRNA levels were associated with decreased progression-free survival (PFS; 4.9 months
vs
6.4,
P
=0.006), overall survival (OS; 10.1
vs
17.0 months,
P
=0.01) and disease control rate (DCR; 57.7%
vs
74.3%;
P
=0.021) compared to patients with low
PKM2
levels. In the validation set, high
PKM2
mRNA levels were also associated with deceased PFS (3.7
vs
5.9 months,
P
=0.006), OS (8.3
vs
16.8 months,
P
=0.003) and DCR (57.7%
vs
70.9%;
P
=0.049) compared to those with low
PKM2
mRNA levels. There was no correlation between the
PKM2
mRNA levels and the PFS (5.6
vs
5.9,
P
=0.43) or the OS (9.8
vs
10.1,
P=
0.51) in the control group. Multivariate analysis revealed high
PKM2
mRNA expression as an independent predictive factor for the poor patients’ outcome.
Conclusions:
PKM2
expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy.</description><subject>692/53/2423</subject><subject>692/699/67/1059/99</subject><subject>692/699/67/1612/1350</subject><subject>692/699/67/322</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antibodies, Monoclonal, Humanized - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bevacizumab</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Carcinoma, Non-Small-Cell Lung - secondary</subject><subject>Carcinoma, Squamous Cell - drug therapy</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Carcinoma, Squamous Cell - secondary</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Deoxycytidine - administration & dosage</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Docetaxel</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gemcitabine</subject><subject>Glutamates - administration & dosage</subject><subject>Guanine - administration & dosage</subject><subject>Guanine - analogs & derivatives</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Pemetrexed</subject><subject>Platinum - administration & dosage</subject><subject>Pneumology</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Survival Rate</subject><subject>Taxoids - administration & dosage</subject><subject>Thyroid Hormone-Binding Proteins</subject><subject>Thyroid Hormones - genetics</subject><subject>Thyroid Hormones - metabolism</subject><subject>Translational Therapeutics</subject><subject>Tumors</subject><subject>Tumors of the respiratory system and mediastinum</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkUuPFCEUhYnROO3ozrUhMe6k5VVNsTGZTHzFMbrQNaEo6KaloARqTP8E_7VMuh3HxBWB8-XcczkAPCV4TTDrXw17s6aY8DWX9B5YkY5RRHoq7oMVxlggLCk-A49K2berxL14CM5oRxljUqzAry8fP1GoC9Rw8GnS-bvN0KUMzc5OqdhYfPXXvh5gTdDlFCsKPlo4B119XCY06GLHI113Nuv5AH2Ec1NtrAX-9HUHJ1t1qe3JwJgiKpMOARkbAgxL3EKjo7H5MXjgdCj2yek8B9_evvl6-R5dfX734fLiChne44oENZg7M3IhqKQ92RiDKe8HJrUdhbMDdWbonDGEYdFJzMwwYme55FKMQjt2Dl4ffedlmOxoWsysg5qzb9sfVNJe_atEv1PbdK0475hgshk8Pxnk9GOxpap9WnJsmRXZENFjspGkUS-PlMmplGzd7QSC1U1xqhWnbopTrbiGP7ub6hb-01QDXpwAXYwOLrdP8-Uv18sNpZw1Dh250qS4tflOuv8N_g0zGrOn</recordid><startdate>20141028</startdate><enddate>20141028</enddate><creator>Papadaki, C</creator><creator>Sfakianaki, M</creator><creator>Lagoudaki, E</creator><creator>Giagkas, G</creator><creator>Ioannidis, G</creator><creator>Trypaki, M</creator><creator>Tsakalaki, E</creator><creator>Voutsina, A</creator><creator>Koutsopoulos, A</creator><creator>Mavroudis, D</creator><creator>Georgoulias, V</creator><creator>Souglakos, J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</scope><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>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</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>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20141028</creationdate><title>PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer</title><author>Papadaki, C ; Sfakianaki, M ; Lagoudaki, E ; Giagkas, G ; Ioannidis, G ; Trypaki, M ; Tsakalaki, E ; Voutsina, A ; Koutsopoulos, A ; Mavroudis, D ; Georgoulias, V ; Souglakos, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-72c04fcd477292816cc0248b39aed7feb2fcb5fcc13075903cbd0fe49497d7af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>692/53/2423</topic><topic>692/699/67/1059/99</topic><topic>692/699/67/1612/1350</topic><topic>692/699/67/322</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antibodies, Monoclonal, Humanized - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bevacizumab</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Carcinoma, Non-Small-Cell Lung - secondary</topic><topic>Carcinoma, Squamous Cell - drug therapy</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - mortality</topic><topic>Carcinoma, Squamous Cell - secondary</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Deoxycytidine - administration & dosage</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Docetaxel</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gemcitabine</topic><topic>Glutamates - administration & dosage</topic><topic>Guanine - administration & dosage</topic><topic>Guanine - analogs & derivatives</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Pemetrexed</topic><topic>Platinum - administration & dosage</topic><topic>Pneumology</topic><topic>Prognosis</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Survival Rate</topic><topic>Taxoids - administration & dosage</topic><topic>Thyroid Hormone-Binding Proteins</topic><topic>Thyroid Hormones - genetics</topic><topic>Thyroid Hormones - metabolism</topic><topic>Translational Therapeutics</topic><topic>Tumors</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Papadaki, C</creatorcontrib><creatorcontrib>Sfakianaki, M</creatorcontrib><creatorcontrib>Lagoudaki, E</creatorcontrib><creatorcontrib>Giagkas, G</creatorcontrib><creatorcontrib>Ioannidis, G</creatorcontrib><creatorcontrib>Trypaki, M</creatorcontrib><creatorcontrib>Tsakalaki, E</creatorcontrib><creatorcontrib>Voutsina, A</creatorcontrib><creatorcontrib>Koutsopoulos, A</creatorcontrib><creatorcontrib>Mavroudis, D</creatorcontrib><creatorcontrib>Georgoulias, V</creatorcontrib><creatorcontrib>Souglakos, J</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Pascal-Francis</collection><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>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Complete (ProQuest Database)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health 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)</collection><collection>ProQuest Central</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Biological Science Journals</collection><collection>Nursing & Allied Health Premium</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Papadaki, C</au><au>Sfakianaki, M</au><au>Lagoudaki, E</au><au>Giagkas, G</au><au>Ioannidis, G</au><au>Trypaki, M</au><au>Tsakalaki, E</au><au>Voutsina, A</au><au>Koutsopoulos, A</au><au>Mavroudis, D</au><au>Georgoulias, V</au><au>Souglakos, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2014-10-28</date><risdate>2014</risdate><volume>111</volume><issue>9</issue><spage>1757</spage><epage>1764</epage><pages>1757-1764</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Background:
Tumour cells exclusively express the embryonic M2 isoform of pyruvate kinase (PKM2). PKM2 expression levels have been correlated with the effect of platinum compounds in cancer cell lines and xenograft models. The potential predictive role of PKM2 in patients with metastatic/advanced non-small-cell lung cancer (NSCLC) receiving platinum-based chemotherapy as first-line was investigated.
Methods:
Quantitative real-time PCR was used to assess the expression of
PKM2
in tumour samples from 148 and 157 NSCLC patients in the training and the validation set, respectively. All patients received front-line platinum-based chemotherapy.
PKM2
mRNA expression was also analysed in a control group of 85 NSCLC patients treated with non-platinum containing regimens.
Results:
In the training set, high
PKM2
mRNA levels were associated with decreased progression-free survival (PFS; 4.9 months
vs
6.4,
P
=0.006), overall survival (OS; 10.1
vs
17.0 months,
P
=0.01) and disease control rate (DCR; 57.7%
vs
74.3%;
P
=0.021) compared to patients with low
PKM2
levels. In the validation set, high
PKM2
mRNA levels were also associated with deceased PFS (3.7
vs
5.9 months,
P
=0.006), OS (8.3
vs
16.8 months,
P
=0.003) and DCR (57.7%
vs
70.9%;
P
=0.049) compared to those with low
PKM2
mRNA levels. There was no correlation between the
PKM2
mRNA levels and the PFS (5.6
vs
5.9,
P
=0.43) or the OS (9.8
vs
10.1,
P=
0.51) in the control group. Multivariate analysis revealed high
PKM2
mRNA expression as an independent predictive factor for the poor patients’ outcome.
Conclusions:
PKM2
expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25233397</pmid><doi>10.1038/bjc.2014.492</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2014-10, Vol.111 (9), p.1757-1764 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4453739 |
| source | MEDLINE; PubMed Central（OA）; Nature; EZB-FREE-00999 freely available EZB journals |
| subjects | 692/53/2423 692/699/67/1059/99 692/699/67/1612/1350 692/699/67/322 Adult Aged Aged, 80 and over Antibodies, Monoclonal, Humanized - administration & dosage Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bevacizumab Biological and medical sciences Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - mortality Carcinoma, Non-Small-Cell Lung - secondary Carcinoma, Squamous Cell - drug therapy Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - secondary Carrier Proteins - genetics Carrier Proteins - metabolism Deoxycytidine - administration & dosage Deoxycytidine - analogs & derivatives Docetaxel Drug Resistance Epidemiology Female Follow-Up Studies Gemcitabine Glutamates - administration & dosage Guanine - administration & dosage Guanine - analogs & derivatives Humans Immunoenzyme Techniques Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - metabolism Lung Neoplasms - mortality Lung Neoplasms - pathology Lymphatic Metastasis Male Medical sciences Membrane Proteins - genetics Membrane Proteins - metabolism Middle Aged Molecular Medicine Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasm Staging Oncology Pemetrexed Platinum - administration & dosage Pneumology Prognosis Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Survival Rate Taxoids - administration & dosage Thyroid Hormone-Binding Proteins Thyroid Hormones - genetics Thyroid Hormones - metabolism Translational Therapeutics Tumors Tumors of the respiratory system and mediastinum |
| title | PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer |
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