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Prognostic significance of cystatin SN associated nomograms in patients with colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is one of most malignant tumors, mainly due to its high rate of metastasis and recurrence. The prognosis of CRC is difficult due to early CRC patients have no specific symptoms. Therefore, it is emergent to identify a biomarker for CRC prognosis. Cystatin SN (CST1) shows elevated expression in many tumors, but its role in CRCs is still unknown. Through immunohistochemistry analysis, we found that CST1 was upregulated in CRC samples. The survival analysis had demonstrated that high CST1 expression was closely associated with poor clinical status, providing that CST1 plays a role in CRC tumorigenesis. Furthermore, nomograms were generated using CST1 levels and other factors to evaluate survival of CRCs. We evaluated the reliabilities of these nomograms using an independent cohort of 141 CRC cases and found that high CST1 expression is linked to low survival, which is consistent with the clinical results. Thus, we could predict the survival of a CRC patient via these nomograms. In addition, the multivariate analysis identified CST1 as an independent prognostic factor for CRCs, providing CST1 as a biomarker for CRC prognosis. Taken together, our studies revealed a close relationship between CST1 and CRCs, suggesting that CST1 possibly acts as a marker for CRC prognosis and a target for CRC therapy.

SUBMITTER: Li T

PROVIDER: S-EPMC5777761 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Prognostic significance of cystatin SN associated nomograms in patients with colorectal cancer.

Li Taiyuan T Xiong Qiangqiang Q Zou Zhen Z Lei Xiong X Jiang Qunguang Q Liu Dongning D

Oncotarget 20171208 70

Colorectal cancer (CRC) is one of most malignant tumors, mainly due to its high rate of metastasis and recurrence. The prognosis of CRC is difficult due to early CRC patients have no specific symptoms. Therefore, it is emergent to identify a biomarker for CRC prognosis. Cystatin SN (CST1) shows elevated expression in many tumors, but its role in CRCs is still unknown. Through immunohistochemistry analysis, we found that CST1 was upregulated in CRC samples. The survival analysis had demonstrated ...[more]

PMID: 29383149

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Project description:AIM:To investigate the associations of the genetic polymorphisms of vascular endothelial growth factor A (VEGF-A) -1498C>T and -634G>C, with the survival of patients with colorectal cancer (CRC). METHODS:A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction (PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A -1498C>T (rs833031) and -634G>C (rs2010963) polymorphisms. Genotyping was validated for VEGF-A -1498C>T polymorphism in 129 patients and for VEGF-A -634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. RESULTS:In the univariate analysis there was a significant association (OR = 0.32; P = 0.048) between genotype CC of the VEGF-A -1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A -1498C>T polymorphism and VEGF-A -634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A -1498C>T polymorphism was significantly correlated with the 5-year survival (P = 0.032), but not significant difference (P = 0.27) was obtained with the VEGF-A -634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT (HR = 2.79) and CC (HR = 4.67) of the polymorphism VEGF-A -1498C>T and the genotype CC (HR = 3.76) of the polymorphism VEGF-A -634C>G acted as an independent prognostic factor for the risk of death in CRC patients. CONCLUSION:The CT and CC genotypes of the VEGF-A -1498C>T and the CC genotype of the VEGF-A -634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.

Project description:BackgroundBone metastases (BM) from colorectal cancer (CRC) are often accompanied by extraosseous metastases, resulting in a dismal prognosis. The present study aimed to determine the risk factors for BM in metastatic CRC (mCRC) and the prognostic factors for CRC patients with BM.MethodsThe study was based on a training cohort of 214 mCRC patients (of which, 101 patients had BM) from our center, and a validation cohort of 511 mCRC patients (of which, 173 patients had BM) from another institute. Risk and prognostic nomograms for BM were developed using univariate and multivariate analyses. The goodness of fit, discrimination, and calibration performance of the nomograms were assessed by R2, concordance statistics (C-statistics), and the calibration curve. The results were internally validated using bootstrap resampling in the training cohort, and externally validated in the validation cohort.ResultsThe novel BM risk nomogram comprised seven variables [degree of tumor differentiation, N-stage, serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), liver metastasis, and lung metastasis]. It showed good performance, with an R2 of 0.447 and a C-statistic of 0.846 [95% confidence interval (CI), 0.793 to 0.898] in the training cohort, and an R2 of 0.325 and a C-statistic of 0.792 (95% CI, 0.750 to 0.834) in the validation cohort. The optimal cutoff value to identify individuals at low or high risk was 56% probability, with a sensitivity of 71.3% and a specificity of 89.4%. The prognostic nomogram included five factors (tumor differentiation, number of extra-BM organs, number of BM lesions, ALP, and LDH), and had an R2 of 0.284 and a C-statistic of 0.723 (95% CI, 0.657 to 0.789) in the training set. This nomogram was externally validated in the validation cohort, with an R2 of 0.182 and a C-statistic of 0.682 (95% CI, 0.638 to 0.726).ConclusionsThe developed and validated risk and prognostic nomograms showed good performance for predicting the occurrence of BM in mCRC as well as the prognosis of CRC patients with BM. The risk nomogram can be used as a cost-effective preliminary screening tool prior to bone scanning.

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Prognostic significance of cystatin SN associated nomograms in patients with colorectal cancer.

Publications

Prognostic significance of cystatin SN associated nomograms in patients with colorectal cancer.

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