Dataset Information

Pim-3 as a potential predictor of chemoradiotherapy resistance in locally advanced rectal cancer patients.

ABSTRACT: Approximately 30% of locally advanced rectal cancer patients might not benefit from chemoradiotherapy; however, the response to neoadjuvant chemoradiotherapy in these cases is difficult to predict. Pim-3 is a member of the provirus integration site for a moloney murine leukemia virus family of proteins that contributes to cell proliferation, survival, and chemotherapy resistance. Therefore, the relationship between Pim-3 expression and response to neoadjuvant chemoradiotherapy in rectal cancer patients is important to evaluate. 175 rectal cancer patients who underwent neoadjuvant treatment enrolled in this study. The relationship between Pim-3 expression on immunohistochemical analysis of rectal cancer tissue, which was obtained before treatment, the response to chemoradiotherapy and survival was investigated. The patients with no Pim-3 expression were more likely to achieve a pathologic complete response to chemoradiotherapy than patients with Pim-3 expression (P?=?0.001). Cox multivariate analysis showed that the significant prognostic factors were Pim-3 expression (P?=?0.003) and the number of neoadjuvant chemotherapy cycles (P?=?0.005) for overall survival. Neoadjuvant chemotherapy cycles (P?=?0.007), adjuvant chemotherapy cycles (P?=?0.004) and pathology types (P?=?0.049) were significant prognostic factors for disease-free survival. Pim-3 is a potential predictive biomarker for the response of rectal cancer to chemoradiotherapy.

SUBMITTER: Zhang RX

PROVIDER: S-EPMC5700084 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Pim-3 as a potential predictor of chemoradiotherapy resistance in locally advanced rectal cancer patients.

Zhang Rong-Xin RX Zhou Zhong-Guo ZG Lu Shi-Xun SX Lu Zhen-Hai ZH Wan De-Sen DS Pan Zhi-Zhong ZZ Wu Xiao-Jun XJ Chen Gong G

Scientific reports 20171122 1

Approximately 30% of locally advanced rectal cancer patients might not benefit from chemoradiotherapy; however, the response to neoadjuvant chemoradiotherapy in these cases is difficult to predict. Pim-3 is a member of the provirus integration site for a moloney murine leukemia virus family of proteins that contributes to cell proliferation, survival, and chemotherapy resistance. Therefore, the relationship between Pim-3 expression and response to neoadjuvant chemoradiotherapy in rectal cancer p ...[more]

PMID: 29167471

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Project description:The aim of the present study was to investigate candidate genes for chemoradiotherapy (CRT) sensitivity in patients with locally advanced rectal cancer (LARC), and the potential mechanisms of their action. A microarray dataset (GSE98959) was obtained from the Gene Expression Omnibus database that included microRNA (miRNA, miR) expression profiling of 22 samples from patients with LARC who had received preoperative radiotherapy and chemotherapy. Of these patients, 10 responded to the treatment and 12 did not. Differentially expressed miRNAs (DEMs) were identified, followed by the construction of an miRNA-gene network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) function analyses were performed on the target genes in the miRNA-gene network. Furthermore, a protein-protein interaction (PPI) network was constructed on the basis of the target genes, followed by GO function enrichment and KEGG pathway analysis. A total of 30 DEMs were identified between the responder and non-responder groups. Thiamine metabolism (including miR-371a-3p) was the pathway with the highest enrichment of DEMs. The pathway that was most markedly enriched in the target genes of upregulated miRNAs was the pluripotency of stem cells pathway, as indicated by phosphoinositide-4,5-bisphosphate 3-kinase γ (PIK3CG) and anaphase-promoting complex subunit 2 (APC2). Pathways in cancer exhibited the highest enrichment in the set of target genes of downregulated miRNAs. KEGG pathway and GO function analysis indicated that target genes in the PPI network were enriched in the glioma pathway and assembled in the intracellular signaling cascade function, as indicated by the proto-oncogene NRAS. miR-371a-3p may be a candidate miRNA for CRT sensitivity in LARC via the thiamine metabolism pathway. PIK3CG and APC2 may contribute to CRT sensitivity via signaling pathways regulating the pluripotency of stem cells. Furthermore, NRAS may serve an important role in mediating CRT sensitivity via an intracellular signaling cascade.

Project description:Background:Inflammatory response and nutritional status are associated with cancer development and progression. The purpose of this study was to explore whether the preoperative fibrinogen-albumin ratio index (FARI) is related to prognosis and chemoradiotherapy outcome of radical surgery after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC). Methods:In total, 123 patients with LARC who underwent radical surgery after NCRT between June 2012 and December 2018 were collected in this study. Time-dependent receiver operating characteristic (ROC) curve analysis was made to evaluate the ability of the markers for forecasting prognosis. The correlation between FARI and clinicopathological parameters was analyzed. The Kaplan-Meier survival analysis, univariate and multivariate analysis based on Cox proportional hazards models, and subgroup analysis were performed to evaluate overall survival (OS) and disease-free survival (DFS). A nomogram was constructed to evaluate the predictive role of FARI in DFS. Results:The ROC curve analysis showed that the ability of FARI on DFS prediction was superior to those of other inflammatory markers and carcinoembryonic antigen (CEA) (P<0.05). Based on the Youden's index, the optimal cut-off value of FARI was 8.8%. High FARI patients (>8.8%) showed a poor response to NCRT and a decreased DFS rate (P<0.05). In addition, multivariate analysis revealed that FARI (HR=3.098, P=0.033), neutrophil-to-lymphocyte ratio (NLR), and postoperative T stage were independent prognostic factors for DFS in TNM stage III LARC patients. However, FARI failed to distinguish patients with poor OS. Harrell's concordance index (C-index) of the nomogram containing FARI (0.807) was obviously higher than that without it (0.732) among LARC patients who underwent radical surgery after NCRT. Moreover, multivariate analysis revealed FARI (OR=3.044, P=0.012) as an independent predictor for response to NCRT. Conclusion:Among LARC patients who underwent radical surgery after NCRT, preoperative FARI is an independent prognostic factor for DFS and an independent predictor for response to NCRT.

Dataset Information

Pim-3 as a potential predictor of chemoradiotherapy resistance in locally advanced rectal cancer patients.

Publications

Pim-3 as a potential predictor of chemoradiotherapy resistance in locally advanced rectal cancer patients.

Similar Datasets

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