A gene expression signature for predicting response to neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma
In patients with pancreatic ductal adenocarcinoma (PDAC), optimal treatment selection, including multimodality regimens such as neoadjuvant chemoradiotherapy (NACRT), can be clinically transformative. Unfortunately, currently no predictive biomarkers are available that can guide the use of NACRT in...
Gespeichert in:
| Veröffentlicht in: | International journal of cancer 2021-02, Vol.148 (3), p.769-779 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 779 |
|---|---|
| container_issue | 3 |
| container_start_page | 769 |
| container_title | International journal of cancer |
| container_volume | 148 |
| creator | Nishiwada, Satoshi Sho, Masayuki Cui, Ya Yamamura, Kensuke Akahori, Takahiro Nakagawa, Kenji Nagai, Minako Nakamura, Kota Takagi, Tadataka Ikeda, Naoya Li, Wei Baba, Hideo Goel, Ajay |
| description | In patients with pancreatic ductal adenocarcinoma (PDAC), optimal treatment selection, including multimodality regimens such as neoadjuvant chemoradiotherapy (NACRT), can be clinically transformative. Unfortunately, currently no predictive biomarkers are available that can guide the use of NACRT in PDAC patients. Accordingly, herein we developed a novel gene signature that can preoperatively predict NACRT‐sensitivity in PDAC patients. Herein, we evaluated the performance of a 10‐gene panel in 749 PDAC cases, which included two public datasets (The Cancer Genome Atlas and International Cancer Genome Consortium; n = 276), and three clinical specimen cohorts (n = 417), and a pre‐NACRT endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) biopsy cohort (n = 56). The potential predictive performance of this signature was evaluated and compared to CA‐19‐9 levels and key clinicopathological factors. We first evaluated the prognostic potential of a 10‐gene panel which significantly predicted overall survival in both public datasets (P |
| doi_str_mv | 10.1002/ijc.33284 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_wiley</sourceid><recordid>TN_cdi_wiley_primary_10_1002_ijc_33284_IJC33284</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2470005804</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5094-c97a92992dafca86b422adf97ebffc5cba8e252b6438963958f9b631adf473bc3</originalsourceid><addsrcrecordid>eNqN0c-L1DAUB_AiijuuHvwHJOBFWbqbpOmPXISl6Lqy4EXP4TV9ncnQJjVJ153_3owzDioI5hJIPnl5yTfLXjJ6ySjlV2arL4uCN-JRtmJU1jnlrHycrdIezWtWVGfZsxC2lDJWUvE0O0tWlrJsVtnDNVmjRYIPs8cQjLMkmLWFuHgkg_MkLfdGR2PXJIHZ2YAkOmLRQb9d7sFGojc4OQ-9cXGDHuYdMZbMYLVHiEaTftERRgI9WqfBa2PdBM-zJwOMAV8c5_Ps64f3X9qP-d3nm9v2-i7XJZUi17IGyaXkPQwamqoTnEM_yBq7YdCl7qBBXvKuEkUjqyK9aZBdVbBkRF10ujjP3h3qzks3Ya_RRg-jmr2ZwO-UA6P-3LFmo9buXjWcM16XqcCbYwHvvi0YoppM0DiOkP5gCYoLQSUtBa0Tff0X3brF2_S8pGpKadlQkdTbg9LeheBxODXDqNrnqVKe6meeyb76vfuT_BVgAhcH8B07NwRt0Go8sf2VVSOYpPvBkm7-X7cmpvicbd1iYzp6dTxqRtz9u2V1-6k99P4DrxHOhw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2470005804</pqid></control><display><type>article</type><title>A gene expression signature for predicting response to neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Access via Wiley Online Library</source><creator>Nishiwada, Satoshi ; Sho, Masayuki ; Cui, Ya ; Yamamura, Kensuke ; Akahori, Takahiro ; Nakagawa, Kenji ; Nagai, Minako ; Nakamura, Kota ; Takagi, Tadataka ; Ikeda, Naoya ; Li, Wei ; Baba, Hideo ; Goel, Ajay</creator><creatorcontrib>Nishiwada, Satoshi ; Sho, Masayuki ; Cui, Ya ; Yamamura, Kensuke ; Akahori, Takahiro ; Nakagawa, Kenji ; Nagai, Minako ; Nakamura, Kota ; Takagi, Tadataka ; Ikeda, Naoya ; Li, Wei ; Baba, Hideo ; Goel, Ajay</creatorcontrib><description>In patients with pancreatic ductal adenocarcinoma (PDAC), optimal treatment selection, including multimodality regimens such as neoadjuvant chemoradiotherapy (NACRT), can be clinically transformative. Unfortunately, currently no predictive biomarkers are available that can guide the use of NACRT in PDAC patients. Accordingly, herein we developed a novel gene signature that can preoperatively predict NACRT‐sensitivity in PDAC patients. Herein, we evaluated the performance of a 10‐gene panel in 749 PDAC cases, which included two public datasets (The Cancer Genome Atlas and International Cancer Genome Consortium; n = 276), and three clinical specimen cohorts (n = 417), and a pre‐NACRT endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) biopsy cohort (n = 56). The potential predictive performance of this signature was evaluated and compared to CA‐19‐9 levels and key clinicopathological factors. We first evaluated the prognostic potential of a 10‐gene panel which significantly predicted overall survival in both public datasets (P < .01, P < .01), and two in‐house patient cohorts (P < .01, P = .04). In the pre‐NACRT EUS‐FNA cohort, we established a radio‐sensitivity gene panel (RSGP) which yielded highly robust (area under the curve [AUC] = 0.91; 95% CI: 0.81‐0.97) for predicting response to gemcitabine‐based NACRT. Multivariate logistic regression analysis revealed that RSGP was an independent predictor for response to NACRT (OR = 2.70; 95% CI: 1.25‐5.85), and this response‐prediction was even more robust when CA‐19‐9 levels were included into the model. In conclusion, we have validated and developed a novel gene signature that is highly robust in predicting response to NACRT, even in preoperative settings, highlighting its clinical significance for optimizing and personalizing treatment strategies in PDAC patients.
What's new?
While the benefits of radiation treatment have been well established in solid cancers, the criteria for optimal indication of radiotherapy in pancreatic ductal adenocarcinoma and the best regimens for its clinical application remain unclear. The availability of biomarkers that could help predict response to radio‐sensitivity before treatment could lead to better‐informed decision‐making. Here, the authors report developing and validating a novel gene expression signature that is highly robust in predicting patient response to neoadjuvant chemoradiotherapy, even in preoperative settings. The results highlight the clinical significance of this gene signature for optimizing and personalizing treatment strategies in patients with pancreatic cancer.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.33284</identifier><identifier>PMID: 32895958</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Adenocarcinoma ; Adult ; Aged ; Aged, 80 and over ; Antigens, Tumor-Associated, Carbohydrate - genetics ; Biopsy ; Cancer ; Carcinoma, Pancreatic Ductal - diagnosis ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - therapy ; Chemoradiotherapy ; Chemotherapy ; Databases, Genetic ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Gemcitabine ; Gene expression ; Gene Expression Profiling - methods ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Expression Regulation, Neoplastic - radiation effects ; gene panel ; Gene Regulatory Networks - drug effects ; Gene Regulatory Networks - radiation effects ; Genomes ; Humans ; Life Sciences & Biomedicine ; Male ; Medical research ; Middle Aged ; neoadjuvant chemoradiotherapy ; Neoadjuvant Therapy - methods ; Oncology ; Pancreas ; Pancreatic cancer ; pancreatic ductal adenocarcinoma ; Pancreatic Neoplasms - diagnosis ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - therapy ; Patients ; predictive biomarker ; Radiation therapy ; radio‐sensitivity ; Science & Technology ; Survival Analysis ; Treatment Outcome ; Ultrasound</subject><ispartof>International journal of cancer, 2021-02, Vol.148 (3), p.769-779</ispartof><rights>2020 Union for International Cancer Control</rights><rights>2020 Union for International Cancer Control.</rights><rights>2021 UICC</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>15</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000568419000001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c5094-c97a92992dafca86b422adf97ebffc5cba8e252b6438963958f9b631adf473bc3</citedby><cites>FETCH-LOGICAL-c5094-c97a92992dafca86b422adf97ebffc5cba8e252b6438963958f9b631adf473bc3</cites><orcidid>0000-0003-1396-6341 ; 0000-0001-6256-4117</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.33284$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.33284$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,781,785,886,1418,27928,27929,45578,45579</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32895958$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nishiwada, Satoshi</creatorcontrib><creatorcontrib>Sho, Masayuki</creatorcontrib><creatorcontrib>Cui, Ya</creatorcontrib><creatorcontrib>Yamamura, Kensuke</creatorcontrib><creatorcontrib>Akahori, Takahiro</creatorcontrib><creatorcontrib>Nakagawa, Kenji</creatorcontrib><creatorcontrib>Nagai, Minako</creatorcontrib><creatorcontrib>Nakamura, Kota</creatorcontrib><creatorcontrib>Takagi, Tadataka</creatorcontrib><creatorcontrib>Ikeda, Naoya</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Baba, Hideo</creatorcontrib><creatorcontrib>Goel, Ajay</creatorcontrib><title>A gene expression signature for predicting response to neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma</title><title>International journal of cancer</title><addtitle>INT J CANCER</addtitle><addtitle>Int J Cancer</addtitle><description>In patients with pancreatic ductal adenocarcinoma (PDAC), optimal treatment selection, including multimodality regimens such as neoadjuvant chemoradiotherapy (NACRT), can be clinically transformative. Unfortunately, currently no predictive biomarkers are available that can guide the use of NACRT in PDAC patients. Accordingly, herein we developed a novel gene signature that can preoperatively predict NACRT‐sensitivity in PDAC patients. Herein, we evaluated the performance of a 10‐gene panel in 749 PDAC cases, which included two public datasets (The Cancer Genome Atlas and International Cancer Genome Consortium; n = 276), and three clinical specimen cohorts (n = 417), and a pre‐NACRT endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) biopsy cohort (n = 56). The potential predictive performance of this signature was evaluated and compared to CA‐19‐9 levels and key clinicopathological factors. We first evaluated the prognostic potential of a 10‐gene panel which significantly predicted overall survival in both public datasets (P < .01, P < .01), and two in‐house patient cohorts (P < .01, P = .04). In the pre‐NACRT EUS‐FNA cohort, we established a radio‐sensitivity gene panel (RSGP) which yielded highly robust (area under the curve [AUC] = 0.91; 95% CI: 0.81‐0.97) for predicting response to gemcitabine‐based NACRT. Multivariate logistic regression analysis revealed that RSGP was an independent predictor for response to NACRT (OR = 2.70; 95% CI: 1.25‐5.85), and this response‐prediction was even more robust when CA‐19‐9 levels were included into the model. In conclusion, we have validated and developed a novel gene signature that is highly robust in predicting response to NACRT, even in preoperative settings, highlighting its clinical significance for optimizing and personalizing treatment strategies in PDAC patients.
What's new?
While the benefits of radiation treatment have been well established in solid cancers, the criteria for optimal indication of radiotherapy in pancreatic ductal adenocarcinoma and the best regimens for its clinical application remain unclear. The availability of biomarkers that could help predict response to radio‐sensitivity before treatment could lead to better‐informed decision‐making. Here, the authors report developing and validating a novel gene expression signature that is highly robust in predicting patient response to neoadjuvant chemoradiotherapy, even in preoperative settings. The results highlight the clinical significance of this gene signature for optimizing and personalizing treatment strategies in patients with pancreatic cancer.</description><subject>Adenocarcinoma</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens, Tumor-Associated, Carbohydrate - genetics</subject><subject>Biopsy</subject><subject>Cancer</subject><subject>Carcinoma, Pancreatic Ductal - diagnosis</subject><subject>Carcinoma, Pancreatic Ductal - genetics</subject><subject>Carcinoma, Pancreatic Ductal - therapy</subject><subject>Chemoradiotherapy</subject><subject>Chemotherapy</subject><subject>Databases, Genetic</subject><subject>Endoscopic Ultrasound-Guided Fine Needle Aspiration</subject><subject>Female</subject><subject>Gemcitabine</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Expression Regulation, Neoplastic - radiation effects</subject><subject>gene panel</subject><subject>Gene Regulatory Networks - drug effects</subject><subject>Gene Regulatory Networks - radiation effects</subject><subject>Genomes</subject><subject>Humans</subject><subject>Life Sciences & Biomedicine</subject><subject>Male</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>neoadjuvant chemoradiotherapy</subject><subject>Neoadjuvant Therapy - methods</subject><subject>Oncology</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 - therapy</subject><subject>Patients</subject><subject>predictive biomarker</subject><subject>Radiation therapy</subject><subject>radio‐sensitivity</subject><subject>Science & Technology</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Ultrasound</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><recordid>eNqN0c-L1DAUB_AiijuuHvwHJOBFWbqbpOmPXISl6Lqy4EXP4TV9ncnQJjVJ153_3owzDioI5hJIPnl5yTfLXjJ6ySjlV2arL4uCN-JRtmJU1jnlrHycrdIezWtWVGfZsxC2lDJWUvE0O0tWlrJsVtnDNVmjRYIPs8cQjLMkmLWFuHgkg_MkLfdGR2PXJIHZ2YAkOmLRQb9d7sFGojc4OQ-9cXGDHuYdMZbMYLVHiEaTftERRgI9WqfBa2PdBM-zJwOMAV8c5_Ps64f3X9qP-d3nm9v2-i7XJZUi17IGyaXkPQwamqoTnEM_yBq7YdCl7qBBXvKuEkUjqyK9aZBdVbBkRF10ujjP3h3qzks3Ya_RRg-jmr2ZwO-UA6P-3LFmo9buXjWcM16XqcCbYwHvvi0YoppM0DiOkP5gCYoLQSUtBa0Tff0X3brF2_S8pGpKadlQkdTbg9LeheBxODXDqNrnqVKe6meeyb76vfuT_BVgAhcH8B07NwRt0Go8sf2VVSOYpPvBkm7-X7cmpvicbd1iYzp6dTxqRtz9u2V1-6k99P4DrxHOhw</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Nishiwada, Satoshi</creator><creator>Sho, Masayuki</creator><creator>Cui, Ya</creator><creator>Yamamura, Kensuke</creator><creator>Akahori, Takahiro</creator><creator>Nakagawa, Kenji</creator><creator>Nagai, Minako</creator><creator>Nakamura, Kota</creator><creator>Takagi, Tadataka</creator><creator>Ikeda, Naoya</creator><creator>Li, Wei</creator><creator>Baba, Hideo</creator><creator>Goel, Ajay</creator><general>John Wiley & Sons, Inc</general><general>Wiley</general><general>Wiley Subscription Services, Inc</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</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>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1396-6341</orcidid><orcidid>https://orcid.org/0000-0001-6256-4117</orcidid></search><sort><creationdate>20210201</creationdate><title>A gene expression signature for predicting response to neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma</title><author>Nishiwada, Satoshi ; Sho, Masayuki ; Cui, Ya ; Yamamura, Kensuke ; Akahori, Takahiro ; Nakagawa, Kenji ; Nagai, Minako ; Nakamura, Kota ; Takagi, Tadataka ; Ikeda, Naoya ; Li, Wei ; Baba, Hideo ; Goel, Ajay</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5094-c97a92992dafca86b422adf97ebffc5cba8e252b6438963958f9b631adf473bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenocarcinoma</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antigens, Tumor-Associated, Carbohydrate - genetics</topic><topic>Biopsy</topic><topic>Cancer</topic><topic>Carcinoma, Pancreatic Ductal - diagnosis</topic><topic>Carcinoma, Pancreatic Ductal - genetics</topic><topic>Carcinoma, Pancreatic Ductal - therapy</topic><topic>Chemoradiotherapy</topic><topic>Chemotherapy</topic><topic>Databases, Genetic</topic><topic>Endoscopic Ultrasound-Guided Fine Needle Aspiration</topic><topic>Female</topic><topic>Gemcitabine</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene Expression Regulation, Neoplastic - radiation effects</topic><topic>gene panel</topic><topic>Gene Regulatory Networks - drug effects</topic><topic>Gene Regulatory Networks - radiation effects</topic><topic>Genomes</topic><topic>Humans</topic><topic>Life Sciences & Biomedicine</topic><topic>Male</topic><topic>Medical research</topic><topic>Middle Aged</topic><topic>neoadjuvant chemoradiotherapy</topic><topic>Neoadjuvant Therapy - methods</topic><topic>Oncology</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 - therapy</topic><topic>Patients</topic><topic>predictive biomarker</topic><topic>Radiation therapy</topic><topic>radio‐sensitivity</topic><topic>Science & Technology</topic><topic>Survival Analysis</topic><topic>Treatment Outcome</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nishiwada, Satoshi</creatorcontrib><creatorcontrib>Sho, Masayuki</creatorcontrib><creatorcontrib>Cui, Ya</creatorcontrib><creatorcontrib>Yamamura, Kensuke</creatorcontrib><creatorcontrib>Akahori, Takahiro</creatorcontrib><creatorcontrib>Nakagawa, Kenji</creatorcontrib><creatorcontrib>Nagai, Minako</creatorcontrib><creatorcontrib>Nakamura, Kota</creatorcontrib><creatorcontrib>Takagi, Tadataka</creatorcontrib><creatorcontrib>Ikeda, Naoya</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Baba, Hideo</creatorcontrib><creatorcontrib>Goel, Ajay</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishiwada, Satoshi</au><au>Sho, Masayuki</au><au>Cui, Ya</au><au>Yamamura, Kensuke</au><au>Akahori, Takahiro</au><au>Nakagawa, Kenji</au><au>Nagai, Minako</au><au>Nakamura, Kota</au><au>Takagi, Tadataka</au><au>Ikeda, Naoya</au><au>Li, Wei</au><au>Baba, Hideo</au><au>Goel, Ajay</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A gene expression signature for predicting response to neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma</atitle><jtitle>International journal of cancer</jtitle><stitle>INT J CANCER</stitle><addtitle>Int J Cancer</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>148</volume><issue>3</issue><spage>769</spage><epage>779</epage><pages>769-779</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><abstract>In patients with pancreatic ductal adenocarcinoma (PDAC), optimal treatment selection, including multimodality regimens such as neoadjuvant chemoradiotherapy (NACRT), can be clinically transformative. Unfortunately, currently no predictive biomarkers are available that can guide the use of NACRT in PDAC patients. Accordingly, herein we developed a novel gene signature that can preoperatively predict NACRT‐sensitivity in PDAC patients. Herein, we evaluated the performance of a 10‐gene panel in 749 PDAC cases, which included two public datasets (The Cancer Genome Atlas and International Cancer Genome Consortium; n = 276), and three clinical specimen cohorts (n = 417), and a pre‐NACRT endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) biopsy cohort (n = 56). The potential predictive performance of this signature was evaluated and compared to CA‐19‐9 levels and key clinicopathological factors. We first evaluated the prognostic potential of a 10‐gene panel which significantly predicted overall survival in both public datasets (P < .01, P < .01), and two in‐house patient cohorts (P < .01, P = .04). In the pre‐NACRT EUS‐FNA cohort, we established a radio‐sensitivity gene panel (RSGP) which yielded highly robust (area under the curve [AUC] = 0.91; 95% CI: 0.81‐0.97) for predicting response to gemcitabine‐based NACRT. Multivariate logistic regression analysis revealed that RSGP was an independent predictor for response to NACRT (OR = 2.70; 95% CI: 1.25‐5.85), and this response‐prediction was even more robust when CA‐19‐9 levels were included into the model. In conclusion, we have validated and developed a novel gene signature that is highly robust in predicting response to NACRT, even in preoperative settings, highlighting its clinical significance for optimizing and personalizing treatment strategies in PDAC patients.
What's new?
While the benefits of radiation treatment have been well established in solid cancers, the criteria for optimal indication of radiotherapy in pancreatic ductal adenocarcinoma and the best regimens for its clinical application remain unclear. The availability of biomarkers that could help predict response to radio‐sensitivity before treatment could lead to better‐informed decision‐making. Here, the authors report developing and validating a novel gene expression signature that is highly robust in predicting patient response to neoadjuvant chemoradiotherapy, even in preoperative settings. The results highlight the clinical significance of this gene signature for optimizing and personalizing treatment strategies in patients with pancreatic cancer.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>32895958</pmid><doi>10.1002/ijc.33284</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-1396-6341</orcidid><orcidid>https://orcid.org/0000-0001-6256-4117</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0020-7136 |
| ispartof | International journal of cancer, 2021-02, Vol.148 (3), p.769-779 |
| issn | 0020-7136 1097-0215 |
| language | eng |
| recordid | cdi_wiley_primary_10_1002_ijc_33284_IJC33284 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via Wiley Online Library |
| subjects | Adenocarcinoma Adult Aged Aged, 80 and over Antigens, Tumor-Associated, Carbohydrate - genetics Biopsy Cancer Carcinoma, Pancreatic Ductal - diagnosis Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - therapy Chemoradiotherapy Chemotherapy Databases, Genetic Endoscopic Ultrasound-Guided Fine Needle Aspiration Female Gemcitabine Gene expression Gene Expression Profiling - methods Gene Expression Regulation, Neoplastic - drug effects Gene Expression Regulation, Neoplastic - radiation effects gene panel Gene Regulatory Networks - drug effects Gene Regulatory Networks - radiation effects Genomes Humans Life Sciences & Biomedicine Male Medical research Middle Aged neoadjuvant chemoradiotherapy Neoadjuvant Therapy - methods Oncology Pancreas Pancreatic cancer pancreatic ductal adenocarcinoma Pancreatic Neoplasms - diagnosis Pancreatic Neoplasms - genetics Pancreatic Neoplasms - therapy Patients predictive biomarker Radiation therapy radio‐sensitivity Science & Technology Survival Analysis Treatment Outcome Ultrasound |
| title | A gene expression signature for predicting response to neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-16T23%3A44%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_wiley&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20gene%20expression%20signature%20for%20predicting%20response%20to%20neoadjuvant%20chemoradiotherapy%20in%20pancreatic%20ductal%20adenocarcinoma&rft.jtitle=International%20journal%20of%20cancer&rft.au=Nishiwada,%20Satoshi&rft.date=2021-02-01&rft.volume=148&rft.issue=3&rft.spage=769&rft.epage=779&rft.pages=769-779&rft.issn=0020-7136&rft.eissn=1097-0215&rft_id=info:doi/10.1002/ijc.33284&rft_dat=%3Cproquest_wiley%3E2470005804%3C/proquest_wiley%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2470005804&rft_id=info:pmid/32895958&rfr_iscdi=true |