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Molecular diagnosis for detecting KRAS mutation in peritoneal washing fluid of pancreatic ductal adenocarcinoma
Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washin...
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| Published in: | Scientific reports 2024-09, Vol.14 (1), p.21732-12, Article 21732 |
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| creator | Shimane, Gaku Nakano, Yutaka Matsuda, Sachiko Kitago, Minoru Masugi, Yohei Nakamura, Kohei Nakamura, Yuki Yagi, Hiroshi Abe, Yuta Hasegawa, Yasushi Hori, Shutaro Tanaka, Masayuki Takemura, Ryo Nishihara, Hiroshi Kitagawa, Yuko |
| description | Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washing cytology for sensitive detection of
KRAS
mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (
P
|
| doi_str_mv | 10.1038/s41598-024-72569-8 |
| format | article |
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KRAS
mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (
P
< 0.001) and in patients with peritoneal dissemination than in those without peritoneal dissemination (
P
< 0.01). The optimal Ct cut-off to predict
KRAS
mutations in IPWF was 36.42 based on a receiver operating characteristic curve. The sensitivity, specificity, and accuracy for molecular diagnosis were 100%, 80.0%, and 85.2%, respectively. Peritoneal dissemination recurrence was significantly more frequent in patients with a positive molecular diagnosis than in those with a negative diagnosis (38.9 vs. 8.0%,
P
= 0.013). The genomic approach might be clinically valuable for a more precise tumor cell detection in IPWF.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-024-72569-8</identifier><identifier>PMID: 39289461</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/721 ; 631/67 ; 692/4020 ; 692/499 ; 692/53 ; Adenocarcinoma ; Adult ; Aged ; Aged, 80 and over ; Ascitic Fluid - pathology ; Carcinoma, Pancreatic Ductal - diagnosis ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - pathology ; Cellular biology ; Cytology ; Diagnosis ; Female ; Humanities and Social Sciences ; Humans ; KRAS ; Male ; Middle Aged ; multidisciplinary ; Mutation ; Nucleic acids ; Pancreas ; Pancreatic cancer ; Pancreatic ductal adenocarcinoma ; Pancreatic Neoplasms - diagnosis ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - pathology ; Peptide nucleic acids ; Peritoneal Lavage ; Peritoneal washing fluid ; Peritoneum ; Polymerase chain reaction ; Proto-Oncogene Proteins p21(ras) - genetics ; ROC Curve ; Science ; Science (multidisciplinary) ; Sensitivity analysis ; Sensitivity and Specificity</subject><ispartof>Scientific reports, 2024-09, Vol.14 (1), p.21732-12, Article 21732</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c422t-dc8e8aeae65ab521adc03d92e13735f529782d84f295edc7522791aff1f5d12b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/3106223355/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3106223355?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39289461$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shimane, Gaku</creatorcontrib><creatorcontrib>Nakano, Yutaka</creatorcontrib><creatorcontrib>Matsuda, Sachiko</creatorcontrib><creatorcontrib>Kitago, Minoru</creatorcontrib><creatorcontrib>Masugi, Yohei</creatorcontrib><creatorcontrib>Nakamura, Kohei</creatorcontrib><creatorcontrib>Nakamura, Yuki</creatorcontrib><creatorcontrib>Yagi, Hiroshi</creatorcontrib><creatorcontrib>Abe, Yuta</creatorcontrib><creatorcontrib>Hasegawa, Yasushi</creatorcontrib><creatorcontrib>Hori, Shutaro</creatorcontrib><creatorcontrib>Tanaka, Masayuki</creatorcontrib><creatorcontrib>Takemura, Ryo</creatorcontrib><creatorcontrib>Nishihara, Hiroshi</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><title>Molecular diagnosis for detecting KRAS mutation in peritoneal washing fluid of pancreatic ductal adenocarcinoma</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washing cytology for sensitive detection of
KRAS
mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (
P
< 0.001) and in patients with peritoneal dissemination than in those without peritoneal dissemination (
P
< 0.01). The optimal Ct cut-off to predict
KRAS
mutations in IPWF was 36.42 based on a receiver operating characteristic curve. The sensitivity, specificity, and accuracy for molecular diagnosis were 100%, 80.0%, and 85.2%, respectively. Peritoneal dissemination recurrence was significantly more frequent in patients with a positive molecular diagnosis than in those with a negative diagnosis (38.9 vs. 8.0%,
P
= 0.013). The genomic approach might be clinically valuable for a more precise tumor cell detection in IPWF.</description><subject>631/208/721</subject><subject>631/67</subject><subject>692/4020</subject><subject>692/499</subject><subject>692/53</subject><subject>Adenocarcinoma</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Ascitic Fluid - pathology</subject><subject>Carcinoma, Pancreatic Ductal - diagnosis</subject><subject>Carcinoma, Pancreatic Ductal - genetics</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Cellular biology</subject><subject>Cytology</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>KRAS</subject><subject>Male</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Mutation</subject><subject>Nucleic acids</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Pancreatic ductal adenocarcinoma</subject><subject>Pancreatic Neoplasms - diagnosis</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Peptide nucleic acids</subject><subject>Peritoneal Lavage</subject><subject>Peritoneal washing fluid</subject><subject>Peritoneum</subject><subject>Polymerase chain reaction</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>ROC Curve</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sensitivity analysis</subject><subject>Sensitivity and Specificity</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9kstu1TAQhiMEolXpC7BAkdiwCdhjO7FXqKq4VBQhcVlbPvY49VGOfbATEG-Pe1JKywJvfJlv_hmP_qZ5SslLSph8VTgVSnYEeDeA6FUnHzTHQLjogAE8vHM-ak5L2ZK6BChO1ePmiCmQivf0uEkf04R2mUxuXTBjTCWU1qd6wxntHOLYfvh89qXdLbOZQ4ptiO0ec5hTRDO1P025umb8tATXJt_uTbQZK2pbt9i5IsZhTNZkG2LamSfNI2-mgqc3-0nz7e2br-fvu8tP7y7Ozy47ywHmzlmJ0qDBXpiNAGqcJcwpQMoGJnz9yCDBSe5BCXR2EACDosZ76oWjsGEnzcWq65LZ6n0OO5N_6WSCPjykPGqTa5cTahSE1WE6lEg5B1TeKTcwLgZH0G1o1Xq9au2Xza5WwzhnM90TvR-J4UqP6YemlBNZu68KL24Ucvq-YJn1LhSL02QipqVoRknPe0IFr-jzf9BtWnKsszpQAIwJUSlYKZtTKRn9bTeU6Gt_6NUfuvpDH_yhZU16dvcftyl_3FABtgKlhuKI-W_t_8j-Bv0fx5c</recordid><startdate>20240917</startdate><enddate>20240917</enddate><creator>Shimane, Gaku</creator><creator>Nakano, Yutaka</creator><creator>Matsuda, Sachiko</creator><creator>Kitago, Minoru</creator><creator>Masugi, Yohei</creator><creator>Nakamura, Kohei</creator><creator>Nakamura, Yuki</creator><creator>Yagi, Hiroshi</creator><creator>Abe, Yuta</creator><creator>Hasegawa, Yasushi</creator><creator>Hori, Shutaro</creator><creator>Tanaka, Masayuki</creator><creator>Takemura, Ryo</creator><creator>Nishihara, Hiroshi</creator><creator>Kitagawa, Yuko</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</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>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20240917</creationdate><title>Molecular diagnosis for detecting KRAS mutation in peritoneal washing fluid of pancreatic ductal adenocarcinoma</title><author>Shimane, Gaku ; Nakano, Yutaka ; Matsuda, Sachiko ; Kitago, Minoru ; Masugi, Yohei ; Nakamura, Kohei ; Nakamura, Yuki ; Yagi, Hiroshi ; Abe, Yuta ; Hasegawa, Yasushi ; Hori, Shutaro ; Tanaka, Masayuki ; Takemura, Ryo ; Nishihara, Hiroshi ; Kitagawa, Yuko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-dc8e8aeae65ab521adc03d92e13735f529782d84f295edc7522791aff1f5d12b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>631/208/721</topic><topic>631/67</topic><topic>692/4020</topic><topic>692/499</topic><topic>692/53</topic><topic>Adenocarcinoma</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Ascitic Fluid - pathology</topic><topic>Carcinoma, Pancreatic Ductal - diagnosis</topic><topic>Carcinoma, Pancreatic Ductal - genetics</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Cellular biology</topic><topic>Cytology</topic><topic>Diagnosis</topic><topic>Female</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>KRAS</topic><topic>Male</topic><topic>Middle Aged</topic><topic>multidisciplinary</topic><topic>Mutation</topic><topic>Nucleic acids</topic><topic>Pancreas</topic><topic>Pancreatic cancer</topic><topic>Pancreatic ductal adenocarcinoma</topic><topic>Pancreatic Neoplasms - diagnosis</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Peptide nucleic acids</topic><topic>Peritoneal Lavage</topic><topic>Peritoneal washing fluid</topic><topic>Peritoneum</topic><topic>Polymerase chain reaction</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>ROC Curve</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sensitivity analysis</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shimane, Gaku</creatorcontrib><creatorcontrib>Nakano, Yutaka</creatorcontrib><creatorcontrib>Matsuda, Sachiko</creatorcontrib><creatorcontrib>Kitago, Minoru</creatorcontrib><creatorcontrib>Masugi, Yohei</creatorcontrib><creatorcontrib>Nakamura, Kohei</creatorcontrib><creatorcontrib>Nakamura, Yuki</creatorcontrib><creatorcontrib>Yagi, Hiroshi</creatorcontrib><creatorcontrib>Abe, Yuta</creatorcontrib><creatorcontrib>Hasegawa, Yasushi</creatorcontrib><creatorcontrib>Hori, Shutaro</creatorcontrib><creatorcontrib>Tanaka, Masayuki</creatorcontrib><creatorcontrib>Takemura, Ryo</creatorcontrib><creatorcontrib>Nishihara, Hiroshi</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><collection>Springer Nature OA/Free Journals</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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>AUTh Library subscriptions: 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>Medical Database</collection><collection>Science Database</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><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Open Access: DOAJ - Directory of Open Access Journals</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shimane, Gaku</au><au>Nakano, Yutaka</au><au>Matsuda, Sachiko</au><au>Kitago, Minoru</au><au>Masugi, Yohei</au><au>Nakamura, Kohei</au><au>Nakamura, Yuki</au><au>Yagi, Hiroshi</au><au>Abe, Yuta</au><au>Hasegawa, Yasushi</au><au>Hori, Shutaro</au><au>Tanaka, Masayuki</au><au>Takemura, Ryo</au><au>Nishihara, Hiroshi</au><au>Kitagawa, Yuko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular diagnosis for detecting KRAS mutation in peritoneal washing fluid of pancreatic ductal adenocarcinoma</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2024-09-17</date><risdate>2024</risdate><volume>14</volume><issue>1</issue><spage>21732</spage><epage>12</epage><pages>21732-12</pages><artnum>21732</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washing cytology for sensitive detection of
KRAS
mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (
P
< 0.001) and in patients with peritoneal dissemination than in those without peritoneal dissemination (
P
< 0.01). The optimal Ct cut-off to predict
KRAS
mutations in IPWF was 36.42 based on a receiver operating characteristic curve. The sensitivity, specificity, and accuracy for molecular diagnosis were 100%, 80.0%, and 85.2%, respectively. Peritoneal dissemination recurrence was significantly more frequent in patients with a positive molecular diagnosis than in those with a negative diagnosis (38.9 vs. 8.0%,
P
= 0.013). The genomic approach might be clinically valuable for a more precise tumor cell detection in IPWF.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>39289461</pmid><doi>10.1038/s41598-024-72569-8</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2024-09, Vol.14 (1), p.21732-12, Article 21732 |
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| source | Open Access: PubMed Central; Publicly Available Content Database; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 631/208/721 631/67 692/4020 692/499 692/53 Adenocarcinoma Adult Aged Aged, 80 and over Ascitic Fluid - pathology Carcinoma, Pancreatic Ductal - diagnosis Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - pathology Cellular biology Cytology Diagnosis Female Humanities and Social Sciences Humans KRAS Male Middle Aged multidisciplinary Mutation Nucleic acids Pancreas Pancreatic cancer Pancreatic ductal adenocarcinoma Pancreatic Neoplasms - diagnosis Pancreatic Neoplasms - genetics Pancreatic Neoplasms - pathology Peptide nucleic acids Peritoneal Lavage Peritoneal washing fluid Peritoneum Polymerase chain reaction Proto-Oncogene Proteins p21(ras) - genetics ROC Curve Science Science (multidisciplinary) Sensitivity analysis Sensitivity and Specificity |
| title | Molecular diagnosis for detecting KRAS mutation in peritoneal washing fluid of pancreatic ductal adenocarcinoma |
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