A Nine-Gene Signature for Predicting the Response to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer
by
In Ja Park 1,†
, Yun Suk Yu 2,†, Bilal Mustafa 3,†, Jin Young Park 2, Yong Bae Seo 2, Gun-Do Kim 2,4, Jinpyo Kim 2, Chang Min Kim 2, Hyun Deok Noh 2, Seung-Mo Hong 5,6, Yeon Wook Kim 6, Mi-Ju Kim 6, Adnan Ahmad Ansari 7, Luigi Buonaguro 8, Sung-Min Ahn 9,* and Chang-Sik Yu 1,*
In Ja Park 1,†, Yun Suk Yu 2,†, Bilal Mustafa 3,†, Jin Young Park 2, Yong Bae Seo 2, Gun-Do Kim 2,4, Jinpyo Kim 2, Chang Min Kim 2, Hyun Deok Noh 2, Seung-Mo Hong 5,6, Yeon Wook Kim 6, Mi-Ju Kim 6, Adnan Ahmad Ansari 7, Luigi Buonaguro 8, Sung-Min Ahn 9,* and Chang-Sik Yu 1,*
1
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
2
CbsBioscience Inc., Daejeon 34036, Korea
3
Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon 21565, Korea
4
Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan 48513, Korea
5
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
6
Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
7
Department of Industrial and Environmental Engineering, Graduate School of Environment, Gachon University, Incheon 21565, Korea
8
Cancer Immunoregulation Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione Pascale”-IRCCS, 80131 Naples, Italy
9
Department of Genome Medicine and Science, College of Medicine, Gachon University, Incheon 21565, Korea
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2020, 12(4), 800; https://doi.org/10.3390/cancers12040800
Received: 18 February 2020 / Revised: 22 March 2020 / Accepted: 25 March 2020 / Published: 26 March 2020
Preoperative chemoradiotherapy (PCRT) and subsequent surgery is the standard multimodal treatment for locally advanced rectal cancer (LARC), albeit PCRT response varies among the individuals. This creates a dire necessity to identify a predictive model to forecast treatment response outcomes and identify patients who would benefit from PCRT. In this study, we performed a gene expression study using formalin-fixed paraffin-embedded (FFPE) tumor biopsy samples from 156 LARC patients (training cohort n = 60; validation cohort n = 96); we identified the nine-gene signature (FGFR3, GNA11, H3F3A, IL12A, IL1R1, IL2RB, NKD1, SGK2, and SPRY2) that distinctively differentiated responders from non-responders in the training cohort (accuracy = 86.9%, specificity = 84.8%, sensitivity = 81.5%) as well as in an independent validation cohort (accuracy = 81.0%, specificity = 79.4%, sensitivity = 82.3%). The signature was independent of all pathological and clinical features and was robust in predicting PCRT response. It is readily applicable to the clinical setting using FFPE samples and Food and Drug Administration (FDA) approved hardware and reagents. Predicting the response to PCRT may aid in tailored therapies for respective responders to PCRT and improve the oncologic outcomes for LARC patients.
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Keywords:
biomarker; locally advanced rectal cancer; preoperative chemoradiotherapy; NanoString analysis
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MDPI and ACS Style
Park, I.J.; Yu, Y.S.; Mustafa, B.; Park, J.Y.; Seo, Y.B.; Kim, G.-D.; Kim, J.; Kim, C.M.; Noh, H.D.; Hong, S.-M.; Kim, Y.W.; Kim, M.-J.; Ansari, A.A.; Buonaguro, L.; Ahn, S.-M.; Yu, C.-S. A Nine-Gene Signature for Predicting the Response to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer. Cancers 2020, 12, 800.
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