Metabolomics evaluation of serum markers for cachexia and their intra-day variation in patients with advanced pancreatic cancer
Cancer cachexia is a multifactorial syndrome characterized by progressive loss of weight and muscle atrophy. Using metabolomics, we investigated serum markers and their intra-day variation in advanced pancreatic cancer patients with cachexia. Patients were enrolled in two groups: those with or witho...
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| Veröffentlicht in: | PloS one 2014-11, Vol.9 (11), p.e113259-e113259 |
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| creator | Fujiwara, Yutaka Kobayashi, Takashi Chayahara, Naoko Imamura, Yoshinori Toyoda, Masanori Kiyota, Naomi Mukohara, Toru Nishiumi, Shin Azuma, Takeshi Yoshida, Masaru Minami, Hironobu |
| description | Cancer cachexia is a multifactorial syndrome characterized by progressive loss of weight and muscle atrophy. Using metabolomics, we investigated serum markers and their intra-day variation in advanced pancreatic cancer patients with cachexia.
Patients were enrolled in two groups: those with or without cachexia. Blood samples collected at 6:30 AM, 11:30 AM, 4:30 PM, and 9:30 PM were analyzed using metabolomics, and serum levels of IL-6, TNF-α, and leptin were measured and compared between the two groups. Intra-day variation was then evaluated.
Twenty-one patients were enrolled in total. In the cachexia group (n = 9), median body weight loss rate over 6 months was greater, performance status was poorer, and anorexia was more severe than in the non-cachexia group (n = 12). Each metabolites level showed substantial intra-day variation, and some of them displayed significant differences between the two groups. Levels of paraxanthine remained markedly lower in the cohort with cachexia at all measurement points. Besides, median IL-6 and TNF-α levels appeared higher and leptin concentration appeared lower in the cachexia group, albeit without statistical significance.
Some metabolites and some serological marker levels were affected by cancer cachexia. Although paraxanthine levels were consistently lower in patients with cachexia, we identified that many metabolites indicated large intra- and inter-day variation and that it might be necessary to pay attention to intra-day variation in metabolomics research. |
| doi_str_mv | 10.1371/journal.pone.0113259 |
| format | Article |
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Patients were enrolled in two groups: those with or without cachexia. Blood samples collected at 6:30 AM, 11:30 AM, 4:30 PM, and 9:30 PM were analyzed using metabolomics, and serum levels of IL-6, TNF-α, and leptin were measured and compared between the two groups. Intra-day variation was then evaluated.
Twenty-one patients were enrolled in total. In the cachexia group (n = 9), median body weight loss rate over 6 months was greater, performance status was poorer, and anorexia was more severe than in the non-cachexia group (n = 12). Each metabolites level showed substantial intra-day variation, and some of them displayed significant differences between the two groups. Levels of paraxanthine remained markedly lower in the cohort with cachexia at all measurement points. Besides, median IL-6 and TNF-α levels appeared higher and leptin concentration appeared lower in the cachexia group, albeit without statistical significance.
Some metabolites and some serological marker levels were affected by cancer cachexia. Although paraxanthine levels were consistently lower in patients with cachexia, we identified that many metabolites indicated large intra- and inter-day variation and that it might be necessary to pay attention to intra-day variation in metabolomics research.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0113259</identifier><identifier>PMID: 25411961</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Anorexia ; Atrophy ; Biology and Life Sciences ; Biomarkers - blood ; Body weight ; Body weight loss ; Cachexia ; Cachexia - blood ; Cachexia - etiology ; Cachexia - mortality ; Caffeine ; Cancer ; Cancer patients ; Cancer therapies ; Care and treatment ; Clinical trials ; Comparative analysis ; Cytokines ; Female ; Gastroenterology ; Hematology ; Homeostasis ; Hospitals ; Humans ; Interleukin 6 ; Interleukin-6 - blood ; Leptin ; Leptin - blood ; Male ; Markers ; Median (statistics) ; Medical prognosis ; Medicine ; Medicine and Health Sciences ; Metabolism ; Metabolites ; Metabolomics ; Metabolomics - methods ; Middle Aged ; Muscles ; Oncology ; Pancreatic cancer ; Pancreatic Neoplasms - blood ; Pancreatic Neoplasms - complications ; Pancreatic Neoplasms - mortality ; Patients ; Physiology ; Quality of life ; Serum levels ; Statistical analysis ; Statistical methods ; Studies ; Survival Analysis ; Theophylline - blood ; Trends ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - blood ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; University graduates ; Variation ; Weight loss</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e113259-e113259</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Fujiwara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Fujiwara et al 2014 Fujiwara et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-a1579dac76476b708aa0c3647ca2653fab7a844ccd595f42dd82392c6c19147d3</citedby><cites>FETCH-LOGICAL-c692t-a1579dac76476b708aa0c3647ca2653fab7a844ccd595f42dd82392c6c19147d3</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/PMC4239056/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239056/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25411961$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gonzalez-Bulnes, Antonio</contributor><creatorcontrib>Fujiwara, Yutaka</creatorcontrib><creatorcontrib>Kobayashi, Takashi</creatorcontrib><creatorcontrib>Chayahara, Naoko</creatorcontrib><creatorcontrib>Imamura, Yoshinori</creatorcontrib><creatorcontrib>Toyoda, Masanori</creatorcontrib><creatorcontrib>Kiyota, Naomi</creatorcontrib><creatorcontrib>Mukohara, Toru</creatorcontrib><creatorcontrib>Nishiumi, Shin</creatorcontrib><creatorcontrib>Azuma, Takeshi</creatorcontrib><creatorcontrib>Yoshida, Masaru</creatorcontrib><creatorcontrib>Minami, Hironobu</creatorcontrib><title>Metabolomics evaluation of serum markers for cachexia and their intra-day variation in patients with advanced pancreatic cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Cancer cachexia is a multifactorial syndrome characterized by progressive loss of weight and muscle atrophy. Using metabolomics, we investigated serum markers and their intra-day variation in advanced pancreatic cancer patients with cachexia.
Patients were enrolled in two groups: those with or without cachexia. Blood samples collected at 6:30 AM, 11:30 AM, 4:30 PM, and 9:30 PM were analyzed using metabolomics, and serum levels of IL-6, TNF-α, and leptin were measured and compared between the two groups. Intra-day variation was then evaluated.
Twenty-one patients were enrolled in total. In the cachexia group (n = 9), median body weight loss rate over 6 months was greater, performance status was poorer, and anorexia was more severe than in the non-cachexia group (n = 12). Each metabolites level showed substantial intra-day variation, and some of them displayed significant differences between the two groups. Levels of paraxanthine remained markedly lower in the cohort with cachexia at all measurement points. Besides, median IL-6 and TNF-α levels appeared higher and leptin concentration appeared lower in the cachexia group, albeit without statistical significance.
Some metabolites and some serological marker levels were affected by cancer cachexia. Although paraxanthine levels were consistently lower in patients with cachexia, we identified that many metabolites indicated large intra- and inter-day variation and that it might be necessary to pay attention to intra-day variation in metabolomics research.</description><subject>Adult</subject><subject>Aged</subject><subject>Anorexia</subject><subject>Atrophy</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers - blood</subject><subject>Body weight</subject><subject>Body weight loss</subject><subject>Cachexia</subject><subject>Cachexia - blood</subject><subject>Cachexia - etiology</subject><subject>Cachexia - mortality</subject><subject>Caffeine</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Clinical trials</subject><subject>Comparative analysis</subject><subject>Cytokines</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Hematology</subject><subject>Homeostasis</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - blood</subject><subject>Leptin</subject><subject>Leptin - blood</subject><subject>Male</subject><subject>Markers</subject><subject>Median (statistics)</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolomics</subject><subject>Metabolomics - methods</subject><subject>Middle Aged</subject><subject>Muscles</subject><subject>Oncology</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - blood</subject><subject>Pancreatic Neoplasms - complications</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Patients</subject><subject>Physiology</subject><subject>Quality of life</subject><subject>Serum levels</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Studies</subject><subject>Survival Analysis</subject><subject>Theophylline - blood</subject><subject>Trends</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor-alpha - blood</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>University graduates</subject><subject>Variation</subject><subject>Weight loss</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0tv1DAQxyMEomXhGyCwhITgsIsdJ05yQaoqHisVVeJ1tWbtycYla2_tZGlPfHWcblptUA8ohzjj3_znkZkkec7ogvGCvbtwvbfQLrbO4oIyxtO8epAcs4qnc5FS_vDgfJQ8CeGC0pyXQjxOjtI8Y6wS7Dj58wU7WLnWbYwKBHfQ9tAZZ4mrSUDfb8gG_C_0gdTOEwWqwSsDBKwmXYPGE2M7D3MN12QH3ux9jSXbeELbBfLbdA0BvQOrUEezVR7jnYpa0eKfJo9qaAM-G9-z5MfHD99PP8_Pzj8tT0_O5kpUaTcHlheVBlWIrBCrgpYAVPH4oSAVOa9hVUCZZUrpvMrrLNW6THmVKqFYxbJC81nycq-7bV2QY--CZGJwz4fOzJLlntAOLuTWm1j4tXRg5I3B-bUEHxNvUZa0YIh0pZUQGWcqhihpqZDmdalUwaLW-zFav9qgVjg0qZ2ITm-saeTa7WQWs6a5iAJvRgHvLnsMndyYoLBtwaLrb_IuaFEKnkb01T_o_dWN1BpiAcbWLsZVg6g8yVjJeJXxLFKLe6j4aIzzEQetNtE-cXg7cYhMh1fdGvoQ5PLb1_9nz39O2dcHbIPQdk1wbT-MV5iC2R5U3oXgsb5rMqNy2JPbbshhT-S4J9HtxeEPunO6XQz-F78MDoo</recordid><startdate>20141120</startdate><enddate>20141120</enddate><creator>Fujiwara, Yutaka</creator><creator>Kobayashi, Takashi</creator><creator>Chayahara, Naoko</creator><creator>Imamura, Yoshinori</creator><creator>Toyoda, Masanori</creator><creator>Kiyota, Naomi</creator><creator>Mukohara, Toru</creator><creator>Nishiumi, Shin</creator><creator>Azuma, Takeshi</creator><creator>Yoshida, Masaru</creator><creator>Minami, Hironobu</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141120</creationdate><title>Metabolomics evaluation of serum markers for cachexia and their intra-day variation in patients with advanced pancreatic cancer</title><author>Fujiwara, Yutaka ; Kobayashi, Takashi ; Chayahara, Naoko ; Imamura, Yoshinori ; Toyoda, Masanori ; Kiyota, Naomi ; Mukohara, Toru ; Nishiumi, Shin ; Azuma, Takeshi ; Yoshida, Masaru ; Minami, Hironobu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-a1579dac76476b708aa0c3647ca2653fab7a844ccd595f42dd82392c6c19147d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Anorexia</topic><topic>Atrophy</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers - blood</topic><topic>Body weight</topic><topic>Body weight loss</topic><topic>Cachexia</topic><topic>Cachexia - blood</topic><topic>Cachexia - etiology</topic><topic>Cachexia - mortality</topic><topic>Caffeine</topic><topic>Cancer</topic><topic>Cancer patients</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Clinical trials</topic><topic>Comparative analysis</topic><topic>Cytokines</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Hematology</topic><topic>Homeostasis</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Interleukin 6</topic><topic>Interleukin-6 - blood</topic><topic>Leptin</topic><topic>Leptin - blood</topic><topic>Male</topic><topic>Markers</topic><topic>Median (statistics)</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metabolomics</topic><topic>Metabolomics - methods</topic><topic>Middle Aged</topic><topic>Muscles</topic><topic>Oncology</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ: Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujiwara, Yutaka</au><au>Kobayashi, Takashi</au><au>Chayahara, Naoko</au><au>Imamura, Yoshinori</au><au>Toyoda, Masanori</au><au>Kiyota, Naomi</au><au>Mukohara, Toru</au><au>Nishiumi, Shin</au><au>Azuma, Takeshi</au><au>Yoshida, Masaru</au><au>Minami, Hironobu</au><au>Gonzalez-Bulnes, Antonio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolomics evaluation of serum markers for cachexia and their intra-day variation in patients with advanced pancreatic cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-20</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e113259</spage><epage>e113259</epage><pages>e113259-e113259</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Cancer cachexia is a multifactorial syndrome characterized by progressive loss of weight and muscle atrophy. Using metabolomics, we investigated serum markers and their intra-day variation in advanced pancreatic cancer patients with cachexia.
Patients were enrolled in two groups: those with or without cachexia. Blood samples collected at 6:30 AM, 11:30 AM, 4:30 PM, and 9:30 PM were analyzed using metabolomics, and serum levels of IL-6, TNF-α, and leptin were measured and compared between the two groups. Intra-day variation was then evaluated.
Twenty-one patients were enrolled in total. In the cachexia group (n = 9), median body weight loss rate over 6 months was greater, performance status was poorer, and anorexia was more severe than in the non-cachexia group (n = 12). Each metabolites level showed substantial intra-day variation, and some of them displayed significant differences between the two groups. Levels of paraxanthine remained markedly lower in the cohort with cachexia at all measurement points. Besides, median IL-6 and TNF-α levels appeared higher and leptin concentration appeared lower in the cachexia group, albeit without statistical significance.
Some metabolites and some serological marker levels were affected by cancer cachexia. Although paraxanthine levels were consistently lower in patients with cachexia, we identified that many metabolites indicated large intra- and inter-day variation and that it might be necessary to pay attention to intra-day variation in metabolomics research.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25411961</pmid><doi>10.1371/journal.pone.0113259</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-11, Vol.9 (11), p.e113259-e113259 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1626535005 |
| source | MEDLINE; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry; DOAJ: Directory of Open Access Journals; EZB Electronic Journals Library |
| subjects | Adult Aged Anorexia Atrophy Biology and Life Sciences Biomarkers - blood Body weight Body weight loss Cachexia Cachexia - blood Cachexia - etiology Cachexia - mortality Caffeine Cancer Cancer patients Cancer therapies Care and treatment Clinical trials Comparative analysis Cytokines Female Gastroenterology Hematology Homeostasis Hospitals Humans Interleukin 6 Interleukin-6 - blood Leptin Leptin - blood Male Markers Median (statistics) Medical prognosis Medicine Medicine and Health Sciences Metabolism Metabolites Metabolomics Metabolomics - methods Middle Aged Muscles Oncology Pancreatic cancer Pancreatic Neoplasms - blood Pancreatic Neoplasms - complications Pancreatic Neoplasms - mortality Patients Physiology Quality of life Serum levels Statistical analysis Statistical methods Studies Survival Analysis Theophylline - blood Trends Tumor necrosis factor Tumor Necrosis Factor-alpha - blood Tumor necrosis factor-TNF Tumor necrosis factor-α University graduates Variation Weight loss |
| title | Metabolomics evaluation of serum markers for cachexia and their intra-day variation in patients with advanced pancreatic cancer |
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