Eukaryotic initiation factor 4A2 (EIF4A2) expression in colorectal cancer and prediction of prognosis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 664-664 ◽  
Author(s):  
Zhan-Hong Chen ◽  
Qinian Wu ◽  
Jiahuan Lu ◽  
Le-zong Chen ◽  
Xiang-yuan Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Free Survival ◽  
Over Expression ◽  
Dld1 Cell ◽  
Colorectal Cancer Patients ◽  
Cancer Tissues ◽  
Disease Free

664 Background: Eukaryotic initiation factor 4A2(EIF4A2) is a member of the eukaryotic initiation factor 4A family and it is one of the protein-synthesis initiation factors, which are involved in the binding of messenger RNA to the ribosome. The prognostic roles of EIF4A2 in breast cancer, melanoma and lung cancer have been studied. However, the clinical significance and biologic role of EIF4A2 in colorectal cancer remain unknown. Methods: We used quantitative real-time polymerase chain reaction to compare expression of eIF4A2 mRNA between 72 paired colorectal cancer tissues and non-tumor colorectal tissues. We used immunohistochemistry to study the expression of EIF4A2 in 310 colorectal cancer patients under surgical resection, 247 of them received curative surgery. We also analyzed correlation between EIF4A2 expression and clinicopathological characteristics. The biological function of EIF4A2 on colorectal cancer cells were determined in vitro by knock-downing EIF4A2 in HCT116 and DLD1 cell lines. We performed MTT tests, colony formation assays, transwell and wound healing assays. Results: EIF4A2 mRNA was significantly higher in colorectal cancer tissues compared to the paired non-tumor colorectal tissues(P = 0.0034). Over-expression of EIF4A2 was prognostic of shorter overall survival(P = 0.002) and shorter disease-free survival(P = 0.042). Over-expression of EIF4A2 was significantly correlated with more TNM stage IV(P = 0.012). Multivariate analysis suggested EIF4A2 as an independent predictor of overall survival (hazard ratio 2.041[95% CI 1.385 to 3.008], P < 0.001) and disease-free survival (hazard ratio 1.537[95% CI 1.003 to 2.355], P = 0.049). Functionally, knockdown of EIF4A2 in HCT116 and DLD1 cell lines exerted tumor-suppressive effects by significantly inhibiting cell proliferation, colony formation,migration and invasion(P < 0.05). Conclusions: EIF4A2 is highly expressed in colorectal cancer and predicts poor prognosis. EIF4A2 could be served as a potential prognostic marker for colorectal cancer patients.

scholarly journals STIL-a novel link in Shh and Wnt signaling, endowing oncogenic and stem like attributes to colorectal cancer

2020 ◽  
Author(s):  
Tapas Pradhan ◽  
Vikas Kumar ◽  
H Evangeline Surya ◽  
R Krishna ◽  
Samu John ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Importance ◽  
Disease Free Survival ◽  
Drug Resistant ◽  
Free Survival ◽  
Over Expression ◽  
Disease Free

AbstractDiscovery of potent gene regulating tumorigenesis and drug resistance is of high clinical importance. STIL is an oncogene, however its molecular insights and role in colorectal oncogenesis are unknown. In this study we have explored role of STIL in tumorigenesis and studied its molecular targets in colorectal cancer (CRC). STIL silencing reduced proliferation and tumor growth in CRC. Further, STIL was found to regulate stemness markers CD133 & CD44 and drug resistant markers Thymidylate synthase, ABCB1 & ABCG2 both in in-vitro and in-vivo CRC models. In addition, over expression of STIL mRNA was found to be associated with reduced disease free survival in CRC cases. To our surprise we observed an Shh independent regulation of stemness and drug resistant genes mediated by STIL. Interestingly, we found an Shh independent regulation of β-catenin mediated by STIL via p-AKT, which partially answers Shh independent regulatory mechanism of CSC markers by STIL. Our study suggest an instrumental role of STIL in molecular manifestation of CRC and progression.

scholarly journals Folate pathway genes linked to mitochondrial biogenesis and respiration are associated with outcome of patients with stage III colorectal cancer

Tumor Biology ◽  
2019 ◽  
Vol 41 (6) ◽  
pp. 101042831984623 ◽  
Author(s):  
Elisabeth Odin ◽  
Arvid Sondén ◽  
Göran Carlsson ◽  
Bengt Gustavsson ◽  
Yvonne Wettergren
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Mitochondrial Biogenesis ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Folate Pathway ◽  
Colorectal Cancer Patients ◽  
Disease Free

5-fluorouracil in combination with the folate leucovorin is the cornerstone in treatment of colorectal cancer. Transport of leucovorin into cells, and subsequent metabolic action, require expression of several genes. The aim was to analyze if tumoral expression of genes putatively involved in leucovorin transport, polyglutamation, or metabolism was associated with outcome of patients with stage III colorectal cancer treated with adjuvant chemotherapy. A total of 363 stage III colorectal cancer patients who received adjuvant bolus 5-fluorouracil + leucovorin alone, or in combination with oxaliplatin according to Nordic bolus regimes were included. Expression of 11 folate pathway genes was determined in tumors using quantitative real-time polymerase chain reaction and related to disease-free survival. The median follow-up time was 5 years. During follow-up, 114 (31%) patients suffered from recurrent disease. A high tumoral expression of the genes SLC46A1/PCFT, SLC19A1/RFC-1, ABCC3/MRP3, GGH, and MTHFD1L, which are involved in folate transport, polyglutamation, or metabolism, was associated with longer disease-free survival of the patients. Each of these genes either encodes mitochondrial enzymes or is being regulated by mitochondrial transcription factors. Expression of the SLC46A1/PCFT gene was most strongly associated with disease-free survival, regardless of treatment regimen. In conclusion, the results show that expression of folate pathway genes are associated with outcome of colorectal cancer patients treated with adjuvant 5-fluorouracil in combination with leucovorin. A prospective study needs to be conducted to determine if expression of these genes can be used to predict response to leucovorin and other folates that are now being tested in clinical studies. Moreover, there seems to be a link between folate metabolism and mitochondrial biogenesis and respiration that deserves further exploration.

scholarly journals The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770365 ◽  
Author(s):  
Peng Wang ◽  
Jianwei Liang ◽  
Zheng Wang ◽  
Huirong Hou ◽  
Lei Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Negative Group ◽  
Tumor Node Metastasis ◽  
Free Survival ◽  
Positive Group ◽  
Node Metastasis ◽  
Tumor Node Metastasis Stage ◽  
Colorectal Cancer Patients ◽  
Disease Free

This retrospective cohort study aimed to discuss the prognostic value of p53 positive in colorectal cancer. A total of 124 consecutive patients diagnosed with colorectal cancer were evaluated at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 1 January 2009 to 31 December 2010. The expression of p53 in colorectal cancer was examined by immunohistochemistry. Based on the expression levels of p53, the 124 patients were divided into a p53 positive group and a p53 negative group. In this study, 72 patients were in the p53 positive group and 52 in the p53 negative group. The two groups were well balanced in gender, age, body mass index, American Society of Anesthesiologists scores, and number of lymph nodes harvested. p53 positive was associated with carcinoembryonic antigen ≥5 ng/mL ( p = 0.036), gross type ( p = 0.037), degree of tumor differentiation ( p = 0.026), pathological tumor stage ( p = 0.019), pathological node stage ( p = 0.004), pathological tumor–node–metastasis stage ( p = 0.017), nerve invasion ( p = 0.008), and vessel invasion ( p = 0.018). Tumor site, tumor size, and pathological pattern were not significantly different between these two groups. Disease-free survival and overall survival in the p53 positive group were significantly shorter than the p53 negative group ( p = 0.021 and 0.025, respectively). Colorectal cancer patients with p53 positive tended to be related to a higher degree of malignancy, advanced tumor–node–metastasis stage, and shorter disease-free survival and overall survival. p53 positive was independently an unfavorable prognostic marker for colorectal cancer patients.

Predictive value of ERCC1 and KRAS in colorectal cancer patients with FOLFOX chemotherapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 588-588
Author(s):  
In Kyu Lee ◽  
Sung-Bong Choi ◽  
DaeYoung Cheung ◽  
Jin Il Kim
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Disease Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Significant Difference ◽  
Colorectal Cancer Patients ◽  
Disease Free

588 Background: To determine the clinical significance of KRAS mutation and ERCC1 overexpression as a predictive factor of resistance in oxaliplatin based treatment. Methods: We retrospectively analyzed the clinicopathologic features, status of KRAS mutation and ERCC1 overexpression of 386 colorectal cancer patients who received curative intent surgery. Among them 84 patients were treated by FOLFOX regimen as the first line. Their disease-free survival and overall survival according to the KRAS and ERCC1 were analyzed. Results: About a quarter of patients (25.5%) were represented KRAS wild type with ERCC1 overexpression. Among the patients who treated by FOLFOX regimen, 73 patients were evaluated both of the KRAS and ERCC1. There were no significant differences of disease-free survival and overall survival according to KRAS status and ERCC1 expression each. Under the subgroup analysis, overall survival of ERCC1 overexpression group in wild type KRAS was poor than ERCC1 negative group (p=.029), but no significant difference was in mutant KRAS group (p=.671). Conclusions: Our results suggest that the KRAS wild type with ERCC1 overexpression would be associated with the resistance of oxaliplatin.If oxaliplatin based chemotherapy would beconsidered, status of KRAS mutation and ERCC1 overexpression should be evaluated.

Immune-related gene signature in predicting prognosis of early-stage colorectal cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3586-3586
Author(s):  
Jia Ke ◽  
Xuanhui Liu ◽  
Xiaofeng Jiang ◽  
Yufeng Chen ◽  
Zerong Cai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Disease Free Survival ◽  
Gene Signature ◽  
Free Survival ◽  
Training Cohort ◽  
Immune Related Genes ◽  
Colorectal Cancer Patients ◽  
Disease Free

3586 Background: Immune-related genes (IRGs) were found to be associated with the prognosis of colorectal cancer (CRC) patients. The aim of this study was to evaluate the impact of IRGs in predicting prognosis of early-stage CRC patients. Methods: According to the CIT microarray data set, 309 early-stage CRC patients were selected for generation of immune-related gene signature (IRGS). 5 independent data sets included 1587 CRC patients with complete prognostic information were divided into a training cohort (566 patients) and two validation cohorts (624 patients in validation-1 and 397 patients in meta-validation). Prognostic analysis were performed to test the predictive value of IRGS. Results: Of 309 early-stage CRC patients, a prognostic immune signature included 23 immune-related genes was constructed. In the training cohort, when considering patients with early tumor stage (I or II), IRGS significantly stratified patients into immune low- vs high-risk groups in terms of disease-free survival (HR = 5.03, 95%CI = 2.94-8.62, P < 0.001). Similarly, higher IRGS was correlated with significantly worse prognosis of early-stage CRC patients in validation-1 (HR = 2.71, 95%CI = 1.44-5.08, P = 0.001) and meta-validation cohort (HR = 3.10, 95%CI = 1.60-6.00, P < 0.001). When compared with Oncotype DX, we found IRGS achieved an improved survival correlation in the training cohort (mean C-index, 0.85 vs 0.65) and the validation-1 cohort (mean C-index, 0.72 vs 0.61). After integrated with clinical characteristics, IRGS remained as an independent prognostic factor after adjusting for T stage and TNM stage of tumor in multivariate analysis (HR = 2.02, 95%CI = 1.61-2.53, P < 0.001). Furthermore, IRGS stratified immune low-risk group patients with adjuvant chemotherapy showed even worse disease-free survival when compared with those without adjuvant chemotherapy (HR = 5.66, 95%CI = 3.153-10.16, P < 0.001 in the training cohort and HR = 3.21, 95%CI = 1.74-5.92, P < 0.001 in the validation-1 cohort). IRGS identified immune high-risk group obtained a significantly higher immune and stromal infiltration (P < 0.001). Particularly, the percentages of Macrophages M2 and CD8+ T cells infiltration were significantly different between these two groups. Conclusions: The proposed prognostic IRGS is a promising system for estimating DFS of colorectal cancer patients, especially those in early-stage. Further studies are needed to evaluate the clinical utility of this system in predicting prognosis of colorectal cancer patients.

Circulating tumor DNA as a promising biomarker of relapse risk for stage II-III colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4079-4079
Author(s):  
Gong Chen ◽  
Feng Wang ◽  
Jun-Jie Peng ◽  
San-Jun Cai ◽  
Ke-Feng Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Curative Resection ◽  
Disease Free Survival ◽  
Early Recurrence ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Free Survival ◽  
Colorectal Cancer Patients ◽  
Disease Free ◽  
Tumor Dna

4079 Background: About 30-50% colorectal cancer patients undergoing a curative resection will experience disease recurrence ultimately. Early detection of recurrence is of great significance for improving the prognosis of colorectal cancer patients. Circulating tumor DNA (ctDNA) has been suggested to be a promising biomarker for postoperative surveillance and prognosis prediction in various cancers including colorectal cancer. However, its performance in predicting early recurrence of colorectal cancer as well as appropriate testing procedures still needs large-scale prospective studies to evaluate. Methods: A total of 246 patients with stage II-III colorectal cancer and underwent curative resection from three clinical centers of China were enrolled in this multicenter prospective cohort study. Tissue samples as well as serial plasma samples before surgery, 7 days and 6 months after surgery and 3 months interval afterwards until recurrence were collected, and subjected to deep targeted-panel sequencing containing 425 cancer-related genes. ctDNA baseline genomic alterations and dynamic changes were analyzed. Its performance in predicting early recurrence was evaluated and compared with other clinical routine investigations, including serum biomarkers CEA and CA199, and CT examination. Results: The ctDNA positive rates at baseline (before surgery) and 7 days after surgery were 72.9% and 18.1% respectively. Among 199 patients with complete survival data, 18 patients were recurrent during follow up period with a median disease-free survival of 280.5 days (114-461 days). At baseline, high clinical stage (p = 0.035), and PTEN mutation (p = 0.009) were significantly associated with increased recurrent risk; while APC mutation (p = 0.04) predicted a decreased recurrent risk. Detection of ctDNA 7 days after surgery [HR: 5.9 (1.94-17.97); p = 0.0004] or any time point before clinical recurrence [HR: 6.14 (2.3-16.38); p < 0.0001] was associated with a significantly higher recurrent risk, and the HR increased accordingly with ctDNA mutation level. In multivariate analyses, ctDNA status was independently associated with relapse after adjusting for known clinicopathological risk factors. CEA status was not significantly (p > 0.4) associated with disease-free survival. A risk scoring model comprising of clinical variables and ctDNA detection after surgery was constructed and can predict 18-month recurrence with an AUC of 0.77. Conclusions: ctDNA is a promising marker of risk stratification, and early relapse detection in resected stage II/III CRC patients. Clinical trial information: NCT03312374 .

scholarly journals INFLUENCE OF SOMATIC MUTATIONS OF KRAS, NRAS, BRAF AND MICROSATELLITE INSTABILITY STATUS ON SURVIVAL OF COLORECTAL CANCER PATIENTS WITH PERITONAL CARCINO

2020 ◽  
Vol 19 (5) ◽  
pp. 61-67
Author(s):  
V. P. Shubin ◽  
Yu. A. Shelygin ◽  
S. I. Achkasov ◽  
O. I. Sushkov ◽  
A. A. Ponomarenko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Peritoneal Carcinomatosis ◽  
Cancer Patients ◽  
Somatic Mutations ◽  
Disease Free Survival ◽  
Free Survival ◽  
The Status ◽  
Colorectal Cancer Patients ◽  
Disease Free

Purpose: to evaluate the effect of somatic mutations of the KRAS, NRAS, BRAF genes and the status of microsatellite instability on the overall and disease-free survival of patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.Material and Methods. From 2012 to 2018, the study included 45 patients who underwent surgery for synchronous peritoneal carcinomatosis with colorectal cancer. In all patients, mutations of the KRAS, NRAS, BRAF genes and MSI status of the tumor and peritoneum metastases were determined using Sanger sequencing, fragment analysis and digital droplet polymerase chain reaction. The effect of mutations on patient survival was evaluated.Results. The prevalence of somatic mutations was 69 % of patients. The discordance between the tumor and peritoneum metastases was 9 %. All tumors and peritoneum metastases were microsatellite stable. KRAS, NRAS, BRAF mutations did not affect the overall and disease-free survival (p=0.87 and p=0.85, respectively).Conclusion. Somatic mutations in the KRAS, NRAS, or BRAF genes are not a prognostic factor affecting the overall and relapse-free survival of colorectal cancer patients with peritoneal carcinomatosis. The molecular status of primary tumor may differ from the status of peritoneal metastasis. It should be taken into account when prescribing targeted drugs. 

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