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Predicting multi-class responses to preoperative chemoradiotherapy in rectal cancer patients.

ABSTRACT: Preoperative chemoradiotherapy (CRT) has become a widely used treatment for improving local control of disease and increasing survival rates of rectal cancer patients. We aimed to identify a set of genes that can be used to predict responses to CRT in patients with rectal cancer.Gene expression profiles of pre-therapeutic biopsy specimens obtained from 77 rectal cancer patients were analyzed using DNA microarrays. The response to CRT was determined using the Dworak tumor regression grade: grade 1 (minimal, MI), grade 2 (moderate, MO), grade 3 (near total, NT), or grade 4 (total, TO).Top ranked genes for three different feature scores such as a p-value (pval), a rank product (rank), and a normalized product (norm) were selected to distinguish pre-defined groups such as complete responders (TO) from the MI, MO, and NT groups. Among five different classification algorithms, supporting vector machine (SVM) with the top 65 norm features performed at the highest accuracy for predicting MI using a 5-fold cross validation strategy. On the other hand, 98 pval features were selected for predicting TO by elastic net (EN). Finally we combined TO- and MI-finder models to build a three-class classification model and validated it using an independent dataset of rectal cancer mRNA expression.We identified MI- and TO-finders for predicting preoperative CRT responses, and validated these data using an independent public dataset. This stepwise prediction model requires further evaluation in clinical studies in order to develop personalized preoperative CRT in patients with rectal cancer.

SUBMITTER: Gim J

PROVIDER: S-EPMC4804643 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Predicting multi-class responses to preoperative chemoradiotherapy in rectal cancer patients.

Gim Jungsoo J Cho Yong Beom YB Hong Hye Kyung HK Kim Hee Cheol HC Yun Seong Hyeon SH Wu Hong-Gyun HG Jeong Seung-Yong SY Joung Je-Gun JG Park Taesung T Park Woong-Yang WY Lee Woo Yong WY

Radiation oncology (London, England) 20160322

<h4>Background</h4>Preoperative chemoradiotherapy (CRT) has become a widely used treatment for improving local control of disease and increasing survival rates of rectal cancer patients. We aimed to identify a set of genes that can be used to predict responses to CRT in patients with rectal cancer.<h4>Methods</h4>Gene expression profiles of pre-therapeutic biopsy specimens obtained from 77 rectal cancer patients were analyzed using DNA microarrays. The response to CRT was determined using the Dw ...[more]

PMID: 27005571

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Project description:The incorporation of chemoradiation prior to resection of the tumour has revolutionized the management of locally advanced rectal cancer. However, a large proportion of these patients are resistant to preoperative treatment schedule. We recently reported that c-Myc gene expression correlates negatively with this resistance in patients with rectal cancer. In this study, we carried out integrated analysis of miRNA and mRNA expression profiling in 45 pre-treatment rectal tumour. Further, expression of miRNAs and c-Myc, and their relationship with clinicopathological factors and patient survival was analysed. As a result, we found that 12 miRNAs were differentially expressed between responder and non-responder rectal cancer patients. Functional classification revealed an association between differentially expressed miRNAs and c-Myc. Subsequent quantitative real-time PCR results showed that both, miRNA-148 and miRNA-375 levels were significantly lower in responder compared to non-responder patients. Notably, the higher level of miRNA-375 was significantly negatively correlated with c-Myc. These results suggest that miRNA-375 and its targeted c-Myc play an important role as predictive biomarker of response to neoadjuvant treatment in patients with locally advanced rectal cancer, but still not suitable for prognosis. Pre-treatment biopsies of 22 patients with LARC were prospectively collected and freshly frozen according to an institutional board-approved protocol. Tumour response was assessed in surgical specimens by pathological examination based on the semi-quantitative tumour regression grading (TRG) system described by Mandard in 1994[36]: TRG1 and TRG2 scores were considered responders, whereas TRG3, TRG4, and TRG5 were classified as non-responders. The inclusion criteria were: histologically proven rectal tumour at a clinical stage UICC II-III (cT3-4/and or N positive), following endorectal ultrasound and/or MRI scan. Patients were excluded if they had the tumour located above 13 cm from the anal verge by rigid rectoscopy, synchronic colonic cancer assessed by colonoscopy, distant metastases by 18FDG PET-CT scan, and suspicion of hereditary colorectal cancer. All patients subsequently received a total dose of 50.4Gy of radiation (28 fractions of 1.8Gy) associated with capecitabine (oral form of 5-FU) with or without oxaliplatine, according to our Hospital Clinical Practice Guidelines. Standardized Surgery was performed, including total mesorectal excision, following an interval of 8-10 weeks after completion of CT/RT.

Dataset Information

Predicting multi-class responses to preoperative chemoradiotherapy in rectal cancer patients.

Publications

Predicting multi-class responses to preoperative chemoradiotherapy in rectal cancer patients.

Similar Datasets

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