Predicting biomarkers of hepatic metastasis in Chinese colorectal cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15545-e15545
Author(s):  
Honghua Peng ◽  
Tianhao Mu ◽  
Yaping Sheng ◽  
Yingmei Li ◽  
Peiguo Cao
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Hepatic Metastasis ◽  
Primary Tumor ◽  
Potential Candidate ◽  
Poor Overall Survival ◽  
Primary Tumors ◽  
Distant Spread ◽  
Colorectal Cancer Patients

e15545 Background: Hepatic metastasis is the most common site of distant spread from colorectal cancer. About 15-25% patients with colorectal cancer harbors hepatic metastasis. The molecular mechanism and predicting biomarkers in colorectal cancer are still not fully understood. Methods: 57 Chinese colorectal cancer patients were enrolled in a cohort study. Samples of primary tumor were collected in these patients and underwent whole exome sequencing. Mutation profiles of primary tumors between the patients with metastasis and those without metastasis were analyzed and compared. Results: In the cohort, 54.4% (31/57) patients presented hepatic metastasis at the time of diagnosis, while 45.6% (26/57) did not. The patients were divided into 2 groups—with hepatic metastasis and without hepatic metastasis. The mutation landscape of primary tumor indicated that the Top 3 most frequently mutated genes of both groups were the same and presented mutated TP53, APC, and KRAS. 2. Interestingly, compared with the patients without hepatic metastasis, the patients with hepatic metastasis presented a higher frequency of mutated TCF7L2 (35.5% vs 3.85%) and TRIM77 (16.1% vs 0%). Moreover, in the patients with hepatic metastasis, the patients with TRIM77 mutation in primary tumor showed a worse overall survival (p < 0.0001). Conclusions: TCF7L2 and TRIM77 may be identified as potential candidate predicting biomarkers for hepatic metastasis in colorectal patients. In addition, mutated TRIM 77 predicted a poor overall survival in hepatic metastasis from colorectal cancer.

scholarly journals Higher titer hepatitis B core antibody predicts a higher risk of liver metastases and worse survival in patients with colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ziyao Li ◽  
Shaofei Li ◽  
Hangbo Tao ◽  
Yixiang Zhan ◽  
Kemin Ni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Hepatitis B ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Hepatic Metastasis ◽  
High Titer ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Colorectal Cancer Patients

Abstract Background There have been controversial voices on if hepatitis B virus infection decreases the risk of colorectal liver metastases or not. This study aims to the find the association between HBV infection and postoperative survival of colorectal cancer and the risk of liver metastases in colorectal cancer patients. Methods Patients who underwent curative surgical resection for colorectal cancer between January 2011 and December 2012 were included. Patients were grouped according to anti-HBc. Differences in overall survival, time to progress, and hepatic metastasis-free survival between groups and significant predictors were analyzed. Results Three hundred twenty-seven colorectal cancer patients were comprised of 202 anti-HBc negative cases and 125 anti-HBc positive cases, and anti-HBc positive cases were further divided into high-titer anti-HBc group (39) and low-titer anti-HBc group (86). The high-titer anti-HBc group had significantly worse overall survival (5-Yr, 65.45% vs. 80.06%; P < .001), time to progress (5-Yr, 44.26% vs. 84.73%; P < .001), and hepatic metastasis-free survival (5-Yr, 82.44% vs. 94.58%; P = .029) than the low-titer group. Multivariate model showed anti-HBc ≥ 8.8 S/CO was correlated with poor overall survival (HR, 3.510; 95% CI, 1.718–7.17; P < .001), time to progress (HR, 5.747; 95% CI, 2.789–11.842; P < .001), and hepatic metastasis-free survival (HR, 3.754; 95% CI, 1.054–13.369; P = .041) in the anti-HBc positive cases. Conclusions Higher titer anti-HBc predicts a potential higher risk of liver metastases and a worse survival in anti-HBc positive colorectal cancer patients.

scholarly journals Higher Titer Hepatitis B Core Antibody Predicts a Higher Risk of Liver Metastasis and Worse Survival in Patients With Colorectal Cancer 

2021 ◽  
Author(s):  
Ziyao Li ◽  
Shaofei Li ◽  
Hangbo Tao ◽  
Yixiang Zhan ◽  
Kemin Ni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Metastasis ◽  
Cancer Patients ◽  
Hepatic Metastasis ◽  
High Titer ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Titer Group ◽  
Colorectal Cancer Patients

Abstract Purpose: This study aims to the find the association between HBV infection and postoperative survival and the risk of liver metastasis in colorectal cancer patients.Methods: Patients who underwent curative surgical resection for colorectal cancer (CRC) between January 2011 and December 2012 were included. Patients were grouped according to anti-HBc. Differences in overall survival (OS), time to progress (TTP) and hepatic metastasis-free survival (HMFS) between groups and significant predictors were analyzed.Results: 327 colorectal cancer patients are comprised of 202 anti-HBc negative cases and 125 anti-HBc positive cases, and anti-HBc positive cases are further divided into high-titer anti-HBc group (39) and low-titer anti-HBc group (86). High-titer anti-HBc group had significantly worse overall survival (5-Yr, 65.45% vs. 80.06%; P < .001), time to progress (5-Yr, 44.26% vs. 84.73%; P < .001) and hepatic metastasis-free survival (5-Yr, 82.44% vs. 94.58%; P = .029) than low-titer group. Multivariate model showed anti-HBc ≥ 8.8 S/CO was correlated with poor overall survival (HR, 3.510; 95% CI, 1.718-7.17; P < .001), time to progress (HR, 5.747; 95% CI, 2.789-11.842; P < .001) and hepatic metastasis-free survival (HR, 3.754; 95% CI, 1.054-13.369; P = .041) in the anti-HBc positive cases.Conclusion: Higher titer anti-HBc predicts a higher risk of liver metastasis and a worse survival in anti-HBc positive colorectal cancer patients.

scholarly journals Downregulation of B3GNT6 Predicts Poor Outcome in Colorectal Cancer Patients

2020 ◽  
Author(s):  
Chen Yang ◽  
Changhao Huang ◽  
Pengwei Zeng ◽  
Heyuan Huang ◽  
Zhikang Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Prognostic Marker ◽  
Protein Level ◽  
Mrna Level ◽  
The Cancer Genome Atlas ◽  
Cancer Tissue ◽  
Poor Overall Survival ◽  
Colorectal Cancer Patients

Abstract Background: B3GNT6 encodes the core 3 synthase in O-glycan biosynthesis. It is commonly expressed in the GI tract, while its clinical significance in colorectal cancer remains largely unknown.Methods: We gathered mRNA transcriptomic sequencing data from 3 Gene Expression Omnibus (GEO) datasets (GSE37182, GSE39582, GSE103512) and The Cancer Genome Atlas (TCGA) to compare the B3GNT6 mRNA level between colorectal cancer tissues and normal tissues and to evaluate its value as a prognostic marker. We further validated this in protein level using online database Human Protein Atlas and with immunohistochemical staining of B3GNT6 with our own cohort. Results: B3GNT6 expression was downregulated in colorectal cancer tissue compared with that in normal tissue in both mRNA and in protein level. Downregulation of B3GNT6 was associated with poor overall survival of colorectal cancer in GSE39582 and in TCGA database. Low B3GNT6 mRNA level was significantly associated with chromosome stable (CIN negative) and KRAS mutated group colorectal cancer patient. GSEA revealed that low B3GNT6 level in colorectal cancer is associated with upregulated proteasome activity.Conclusions: Downregulated B3GNT6 was correlated with poor overall survival of colorectal cancer patients. B3GNT6 could be used as a good prognostic marker in colorectal cancer.

A cohort study on the molecular mechanism of distinct therapeutic effects and prognosis in Chinese colorectal cancer patients who underwent neoadjuvant or surgical therapies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15544-e15544
Author(s):  
Ye Xu ◽  
Tianhao Mu
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cohort Study ◽  
Cancer Patients ◽  
Molecular Mechanism ◽  
Therapeutic Effects ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Family Histories ◽  
Colorectal Cancer Patients

e15544 Background: Colorectal cancer is one of the most common and lethal types of cancer in the world. However, the molecular mechanism of colorectal cancer and predicting biomarkers for prognosis are still not fully understood. Methods: Here, we investigated a cohort study to explore the genetic alteration of Chinese colorectal cancer patients. Primary tumors and metastatic tumors were collected and performed with whole exome sequencing. Distinct therapeutic effects of patients were recorded and analyzed. Overall survival of patients was also collected. Results: 57 patients with colorectal cancer (CRC) were enrolled in this study. The mutation landscape of primary tumors showed that the TOP 10 most frequently mutated genes were APC, TP53, KRAS, FRG1, SOX9, PIK3CA, MUC12, SMAD4, MUC4, and DNAH9. The main genetic mutation type was missense. Both primary tumors and metastatic tumors shared the feature of mutated TP53, APC, and KRAS. However, the primary tumors harbored higher mutated FMN2, PLXNB2, DSCAM, SSPO, and PCDHA13, while the metastatic tumors harbored RYR2, RAB15, WNK1, MUC16, and HERC2. Moreover, APC mutation showed a better overall survival (p = 0.029). Co-mutation of APC and FRG1 also presented a better overall survival than one-mutation or none-mutation types (p = 0.029). In contrast, ARID3A mutation (p < 0.001), NUDT6 mutation (p < 0.0099), ZNF717 mutation (p = 7e-04). Curative surgery showed better overall survival than palliative surgery (p = 0.042). However, EBV infection showed no significant relation to overall survival (p = 0.89). In addition, patients harboring FRG1 or CEL mutation were more sensitive to chemotherapy (p = 0.01 and p = 0.02 respectively), while TMB was not significantly related to the effects of chemotherapy. Interestingly, somatic mutations, including NEURL4, DLGAP5, EML1, MBD3L1, SETBP1, TMC4, YTHDC1, PLXNB2, ARHGAP8, and CHD2 were found to be significantly related to patients with family histories (p < 0.05). Conclusions: In this study, we investigated the mutation landscape of primary tumors and metastatic tumors of Chinese colorectal cancer patients. Moreover, the associations between prognosis and different factors, including genetic mutations, surgery strategies, TMB, EBV, and family histories were explored, which may help shed light on better clinical treatment for colorectal cancer in the future.

scholarly journals Deciphering the potential value of 5-fluorouracil metabolic enzymes in predicting prognosis and treatment response of colorectal cancer patients

2018 ◽  
Vol 33 (2) ◽  
pp. 180-188 ◽  
Author(s):  
Kinjal K. Gajjar ◽  
Hemangini H. Vora ◽  
Toral P. Kobawala ◽  
Trupti I. Trivedi ◽  
Nandita R. Ghosh
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Metabolic Enzymes ◽  
Immunohistochemical Localization ◽  
Response To Treatment ◽  
Poor Overall Survival ◽  
Predictive Values ◽  
Potential Efficacy ◽  
Colorectal Cancer Patients

Introduction: 5-flourouracil (5-FU) is one of the standard chemotherapeutic drugs used today in the treatment of colorectal cancer patients. Disruption of 5-FU metabolic pathway may contribute to altered effectiveness towards 5-FU-based therapy. Hence, the study of 5-FU metabolizing enzymes might have the potential efficacy to predict survival and response to treatment in colorectal cancer patients. Materials and methods: Immunohistochemical localization of 5-FU metabolic enzymes (TS, MTHFR, DPYD, and TP) was evaluated in 143 untreated patients with colorectal cancer; their prognostic and predictive values were also evaluated. Results: Immuno-positivity for TS, MTHFR, DPYD, and TP was observed in 77%, 75%, 88%, and 96% of colorectal cancer patients, respectively. Univariate survival analysis in total patients showed that low DPYD expression significantly predicted adverse overall survival ( P=0.042). Moreover, subgroup of colon cancer patients with low TS expression was associated with unfavorable prognosis. TP expression also emerged as a prognosticator in the subgroup of early and advanced stage patients. Additionally, when effect of co-expression of 5-FU metabolic enzymes was evaluated in total patients, low coexpression of all four proteins was predictive of poor overall survival than for individuals expressing high coexpression of these proteins ( P=0.045). In contrast, none of the 5-FU metabolic enzymes—either singly or on coexpression—emerged as a useful biomarker of potential therapeutic value when evaluated in the subgroup of patients treated with 5-FU alone or 5-FU plus oxaliplatin. Conclusion: The above findings suggest that coexpression of 5-FU metabolic enzymes possess significant prognostic value and could be useful biomarkers in colorectal cancer patients.

High Expression of sLex Associated with Poor Survival in Argentinian Colorectal Cancer Patients

2014 ◽  
Vol 29 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Ariel Zwenger ◽  
Martin Rabassa ◽  
Sandra Demichelis ◽  
Gabriel Grossman ◽  
Amada Segal-Eiras ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Normal Mucosa ◽  
Poor Survival ◽  
Primary Tumors ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph ◽  
Colorectal Cancer Patients

Aim Colorectal cancer (CRC) is one of the most prevalent malignancies in Argentina with 11,043 new cases and 6,596 deaths estimated to have occurred in 2008. The present study was developed to clarify the differential expression of MUC1, MUC2, sLex, and sLea in colorectal cancer patients and their relationship with survival and clinical and histological features. Methods Ninety primary tumor samples and 43 metastatic lymph nodes from CRC patients were studied; follow-up was documented. Twenty-six adenoma and 68 histological normal mucosa specimens were analyzed. An immunohistochemical approach was applied and statistical analysis was performed. Results In tumor samples, MUC1, sLea, and sLex were highly expressed (94%, 67%, and 91%, respectively); also, we found a significantly increased expression of the 3 antigens in primary tumors and metastatic lymph nodes compared with normal mucosa and adenomas. MUC2 was expressed in 52% of both normal mucosa and CRC samples; this reactivity significantly decreased in metastatic lymph nodes (p<0.05). A multiple comparison analysis showed that MUC1 and sLex discriminated among 3 groups: normal, adenoma, and CRC tissues. The increase of sLex expression showed an association with recurrence, and survival analysis showed that a high sLex staining was significantly associated with a poor survival. By multivariate analysis MUC1 inmunoreactivity correlated positively and significantly with tumor size, while MUC2 expression showed the opposite correlation. Conclusions The correlation of sLex overexpression in primary tumors and metastatic lymph nodes, the discrimination among the normal, adenoma, and CRC groups based on sLex expression, as well as its association with recurrence and survival, all suggest a prognostic role of sLex in Argentinian CRC patients.

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