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A retrospective cohort study of clinical value of PRL-3 in stage III human colorectal cancer.

ABSTRACT:

Abstract

The aim of this study was to investigate the expression of phosphatase of regenerating live-3 (PRL-3) in human stage III colorectal cancer (CRC) and to evaluate its correlation with metachronous liver metastasis (MLM) and prognosis.The retrospective cohort study included 116 stage III CRC primary tumors and 60 normal colorectal tissues. PRL-3 expression was measured by immunohistochemistry. We investigated the correlation of PRL-3 with clinicopathologic features by the chi-square test. The association of PRL-3 expression with MLM was assessed by binary logistic regression. Overall survival (OS) and disease-free survival (DFS) between patients with positive PRL-3 expression and those with negative PRL-3 expression were compared by the Kaplan-Meier method and Cox proportional hazards regression model.We found that 32.8% of stage III CRC primary tumors were PRL-3 positive, and 15.0% of normal colorectal epithelia showed high PRL-3 expression (P = .012). Seventeen tumors (47.2%) among 36 cases that developed MLM were PRL-3 positive, and only 21 tumors (26.3%) in the 80 cases that did not develop MLM had positive PRL-3 expression (P = .026). PRL-3 expression was associated with MLM (P = .028). Patients with positive expression of PRL-3 showed a significantly shorter OS (40.32 ± 3.97 vs 53.96 ± 2.77 months, P = .009) and DFS (34.97 ± 4.30 vs 44.48 ± 2.89 months, P = .036). A multivariate analysis indicated that PRL-3 expression was an independent unfavorable prognostic factor for OS (P = .007).Our study suggested that high PRL-3 expression is an independent risk factor for MLM and poor prognosis. PRL-3 is expected to be a promising biomarker for predicting the incidence of MLM and prognosis in patients with stage III CRC.

SUBMITTER: Liu C

PROVIDER: S-EPMC8084011 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Distant metastasis is the major causes of death in colorectal cancer (CRC) patients. In order to identify genes influencing the prognosis of patients with CRC, we compared gene expression in primary tumors with and without distant metastasis using an oligonucleotide microarray. We also examined the expression of the candidate gene in 100 CRC patients by quantitative real-time reverse transcription PCR and studied the relationship between its expression and the prognosis of patients with CRC. As a result, we identified MUC12 as a candidate gene involved in metastasis processes by microarray analysis. Quantitative real-time reverse transcription PCR showed that MUC12 expression was significantly lower in cancer tissues than in adjacent normal tissues (P < 0.001). In stage II and stage III CRC, patients with low expression showed worse disease-free survival (P = 0.038). Multivariate analysis disclosed that MUC12 expression status was an independent prognostic factor in stage II and stage III CRC (relative risk, 9.532; 95% confidence interval, 2.303-41.905; P = 0.002). This study revealed the prognostic value of MUC12 expression in CRC patients. Moreover, our result suggests MUC12 expression is a possible candidate gene for assessing postoperative adjuvant therapy for CRC patients. Total of 111 microarray datasets (77 for LCM samples, and 17 pairs for homogenized samples from tumor and adjacent tissues) were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software together with BioConductor package, as described previously. Then, the gene expression levels were log2-transformed, and 62 control probe sets were removed for further analysis. In order to identify a set of genes associated with development of metastatic recurrence, we performed Wilcoxon rank-sum test for gene expression differences of 54,613 probe sets between recurrence and non-recurrence groups. Similarly, Wilcoxon singed-rank test was conducted to select genes which showed significant expression difference between tumor and adjacent tissue. Then, we selected a set of genes that satisfied both of above two criteria.

Project description:BACKGROUND:The development of colorectal cancer (CRC) is a complicated multistep process that involves an accumulation of mutations in tumor suppressor genes and oncogenes. In the process of DNA replication, base mismatch often occurs due to various factors leading to abnormal expression of mismatch repair genes (MMR), among which MLH1 and MSH2 are the most important. Recently, numerous studies indicated that MLH1/MSH2 phenotype is associated with CRC. We wanted to elucidate the role of MLH1/MSH2 in the prediction and prognosis of CRC through long-term clinical observation. AIM:To evaluate the prognostic and predictive significance of MLH1/MSH2 in patients with stage II-III CRC using immunohistochemical analysis and GeneScan. METHODS:Specimens from 681 patients with CRC (395 stage II and 286 stage III, 387 males and 294 females) who underwent curative surgical resection from 2013 to 2016 were tested. Immunohistochemistry was used to analyze MMR status and the microsatellite status of 133 patients was determined by GeneScan analysis. RESULTS:Five hundred and fifty (80.76%) patients were MLH1/MSH2 positive and 131 (19.24%) were negative by immunohistochemistry. MLH1/MSH2-positive tumors were significantly more frequent in the colon than in the rectum, and had poor differentiation and less mucin production (P < 0.05). Patients of different groups did not differ in terms of age, gender, tumor size, tumor stage, lymphocytic infiltration, or circumscribed margin. MLH1/MSH2-negative patients had a more favorable OS than MLH1/MSH2-positive patients (P < 0.001). Univariate and multivariate analyses demonstrated MLH1/MSH2 expression as an independent prognostic and predictive factor for stage II/III CRC. MLH1/MSH2 expression was a strong prognostic factor in all patients [P < 0.001, hazard ratio (HR) = 4.064, 95%CI: 2.241-7.369]. Adjuvant chemotherapy had a greater correlation with survival advantage in MLH1/MSH2-negative patients with stage III disease (P < 0.001, HR = 7.660, 95%CI: 2.974-15.883). However, patients with stage II disease or MLH1/MSH2-positive patients with stage III disease did not benefit from adjuvant chemotherapy. GeneScan analysis demonstrated that among 133 patients, 105 (78.95%) were microsatellite stable, and 28 (21.05%) had microsatellite instability (MSI), including 18 (13.53%) with high MSI and 10 (7.52%) with low MSI. This is consistent with the immunohistochemical results. CONCLUSION:MLH1/MSH2 phenotype constitutes a pathologically and clinically distinct subtype of sporadic CRC. MLH1/MSH2 is an independent prognostic and predictive factor for outcome of stage II-III CRC.

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A retrospective cohort study of clinical value of PRL-3 in stage III human colorectal cancer.

Abstract

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