Expressions of 10 genes as candidate predictors of recurrence in stage�III colon cancer patients receiving adjuvant oxaliplatin‑based chemotherapy

Abstract

Approximately 30% patients with stage III colon cancer (CC) develop local recurrence and/or distant metastasis, even if postoperative adjuvant chemotherapy with oxaliplatin plus 5-fluorouracil and leucovorin (5-FU/LV) has been completed. In the present study, molecular analysis was performed to identify molecular markers of tumor recurrence in patients with stage III CC receiving oxaliplatin-based adjuvant chemotherapy. The FACOS study was conducted as a phase II study to evaluate the safety and efficacy of oxaliplatin-based treatment for stage III CC patients. Of the 132 CC patients enrolled in the present study, gene expression analysis using a microarray was conducted in 51 patients. Of these 51 patients, 6 developed recurrence within 5 years. The topmost 5% genes that showed differential expressions between cases that developed/did not develop recurrence were selected, and a set of predictive molecular markers for recurrence was identified. Of the 34,694 genes in the microarray, 1,734 genes were extracted as topmost 5% genes showing differential expressions between cases with and without recurrence. Among these, 10 genes, including ADH1A, ADH1C, CA12, CHP2, HMGCS2, SNAR-A1, TPI1, MS4A12, PLA2G10 and PTPRO , were identified as markers that could clearly divide patients with and without recurrence. Although several prediction models of tumor recurrence have been reported for CC, the set of 10 genes that the present study identified may be useful to predict the risk of recurrence in stage III CC patients receiving oxaliplatin-based adjuvant chemotherapy. Based on these results, high-risk patients with CC should be carefully observed to detect tumor recurrence during the follow-up period.

Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR

“…Mechanistically, overexpression of CHP2 activated AKT signaling and suppressed the transactivation of the forkhead box O3 (FOXO3/FOXO3a) transcription factor in breast cancer [29]. Besides, a study conducted 10-gene signature including CHP2 found that high expression of CHP2 was associated with the recurrence of COAD [30]. While our results identified CHP2 was lower expressed in CRC cell lines, which was constant with the results of TCGA.…”

Identification of microRNA-451a as a Novel Circulating Biomarker for Colorectal Cancer Diagnosis

“…Our data enhanced the relationship between Klf4 and CA1, indicating that the two are most likely coexpressed in colorectal cancer cells. Other genes, such as ADH1B [ 35 ], GUCA2A [ 36 ], SCNN1B, and CHP2 [ 37 , 38 ], were also reported to play a role in CRC cell differentiation and tumorigenesis. Taken these results together, our analysis identified DE-genes that are involved in different stages of CRC.…”

Identification of Down-Regulated ADH1C is Associated With Poor Prognosis in Colorectal Cancer Using Bioinformatics Analysis

“…In addition, the latest study showed that ADH1C is down-regulated in familial adenomatous polyposis case adenomas ( Thiruvengadam et al, 2019 ), but up-regulated in patients with ulcerative colitis ( Low et al, 2019 ). Kumamoto et al (2019) revealed that ADH1C could predict the recurrence of stage III CRC in patients who accept chemotherapy treatment. Our study is the first to show a correlation between the lower expression level of ADH1C and worse prognostic of CRC patients.…”