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A four-microRNA classifier as a novel prognostic marker for tumor recurrence in stage II colon cancer.

ABSTRACT: About 20 percent of TNM-stage II colon cancer patients who are treated by surgical resection develop recurrence, and adjuvant chemotherapy in this group is still debated among researchers and clinicians. Currently, adverse histopathological and clinical factors are used to select patients for adjuvant chemotherapy following surgery. However, additional biomarkers to classify patients at risk of recurrence are needed. We have conducted a study using fresh frozen tumor tissue from 54 TNM-stage II colon cancer patients and performed microRNA profiling using next-generation sequencing. For the selection of the prognostic microRNAs, a LASSO Cox Regression model was employed. For the validation, we used the publically available TCGA-COAD cohort (n?=?122). A prognostic panel of four micorRNAs (hsa-miR-5010-3p, hsa-miR-5100, hsa-miR-656-3p and hsa-miR-671-3p) was identified in the study cohort and validated in the TCGA-COAD cohort. The four-microRNA classifier successfully identified high-risk patients in the study cohort (P?

SUBMITTER: Jacob H

PROVIDER: S-EPMC5906690 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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A four-microRNA classifier as a novel prognostic marker for tumor recurrence in stage II colon cancer.

Jacob Havjin H Stanisavljevic Luka L Storli Kristian Eeg KE Hestetun Kjersti E KE Dahl Olav O Myklebust Mette P MP

Scientific reports 20180418 1

About 20 percent of TNM-stage II colon cancer patients who are treated by surgical resection develop recurrence, and adjuvant chemotherapy in this group is still debated among researchers and clinicians. Currently, adverse histopathological and clinical factors are used to select patients for adjuvant chemotherapy following surgery. However, additional biomarkers to classify patients at risk of recurrence are needed. We have conducted a study using fresh frozen tumor tissue from 54 TNM-stage II ...[more]

PMID: 29670141

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Project description:Background The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Results The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P=0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein-negative colon cancers than among the 276 (87.9%) with CDX2 protein-positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P=0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P=0.003) and in the validation data set (51% among 15 patients with CDX2-negative tumors vs. 80% among 106 patients with CDX2-positive tumors, P=0.004). In a pooled database of all patient cohorts, the rate of 5-year disease-free survival was higher among 23 patients with stage II CDX2-negative tumors who were treated with adjuvant chemotherapy than among 25 who were not treated with adjuvant chemotherapy (91% vs. 56%, P=0.006). Conclusions Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who appeared to benefit from adjuvant chemotherapy. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.).

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A four-microRNA classifier as a novel prognostic marker for tumor recurrence in stage II colon cancer.

Publications

A four-microRNA classifier as a novel prognostic marker for tumor recurrence in stage II colon cancer.

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