• Genomics & Informatics
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• 제17권4호
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• pp.42.1-42.6
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• 2019

Robust identification of genetic alterations is important for the diagnosis and subsequent treatment of tumors. Screening for genetic alterations using tumor tissue samples may lead to biased interpretations because of the heterogeneous nature of the tumor mass. Liquid biopsy has been suggested as an attractive tool for the non-invasive follow-up of cancer treatment outcomes. In this study, we aimed to verify whether the mutations identified in primary tumor tissue samples could be consistently detected in plasma cell-free DNA (cfDNA) by digital polymerase chain reaction (dPCR). We first examined the genetic alteration profiles of three colorectal cancer (CRC) tissue samples by targeted next-generation sequencing (NGS) and identified 11 non-silent amino acid changes across six cancer-related genes (APC, KRAS, TP53, TERT, ARIDIA, and BRCA1). All three samples had KRAS mutations (G12V, G12C, and G13D), which were well-known driver events. Therefore, we examined the KRAS mutations by dPCR. When we examined the three KRAS mutations by dPCR using tumor tissue samples, all of them were consistently detected and the variant allele frequencies (VAFs) of the mutations were almost identical between targeted NGS and dPCR. When we examined the KRAS mutations using the plasma cfDNA of the three CRC patients by dPCR, all three mutations were consistently identified. However, the VAFs were lower (range, 0.166% to 2.638%) than those obtained using the CRC tissue samples. In conclusion, we confirmed that the KRAS mutations identified from CRC tumor tissue samples were consistently detected in the plasma cfDNA of the three CRC patients by dPCR.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6253-6255
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• 2014

Background: Colorectal cancer (CRC) is considered to be a main cause of malignancy-related death in the world, being commonly diagnosed in both men and women. It is the third leading cause of cancer dependent death in the world and there are one million new cases diagnosed per year. In Iran the incidence of colorectal cancer has increased during the last 25 years and it is the fifth cause of cancer in men and the third in women. Materials and Methods: In this article we analyzed the survival of 475 colorectal patients of Taleghani hospital in Tehran with the semi-parametric competing-risks model. Results: There were 55% male cases and at the time of the diagnosis most of the patients were between 48 and 67years old. The probability of a patient death from colorectal cancer with survival of more than 25 years was about 0.4. Body mass index, height, tumour site and gender had no influence. Conclusions: According to these data and by using semi-parametric competing-risks method, we found out that only age at diagnosis has a significant effect on these patient survival time.

• 한국발생생물학회지:발생과생식
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• 제20권1호
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• pp.1-10
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• 2016

Molecular targeting for the altered signaling pathways has been proven to be effective for the treatment of many types of human cancer, including colorectal cancer (CRC). The dual phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 has shown to exhibit potent antitumor activity against solid tumors. Autophagy is a cellular lysosomal catabolic process to maintain metabolic homeostasis, which has been known to be induced in response to many therapeutic agents in cancer cells. This process is negatively regulated by mTOR and often acts as prosurvival or prodeath mechanism following cancer therapeutics. The current study was designed to investigate the antiproliferation activity of BEZ235 and to evaluate the role of autophagy induced by BEZ235 using HCT15 CRC cells bearing ras oncogene mutation. We found that BEZ235 decreases cell viability, which was mostly dependent on $G_1$ arrest of cell cycle via suppression of cyclin A expression. BEZ235 affects PI3K/Akt/mTOR signaling pathway by increasing the phosphorylation of AKT at $Ser^{473}$ and RAS/RAF/MEK/ERK pathway by decreasing the phosphorylation of ERK at $Tyr^{204}$. BEZ235 also stimulated autophagy induction as evidenced by the increased expression of LC3-II and abundant acidic vesicular organelles (AVOs) in the cytoplasm. In addition, the combination of BEZ235 with autophagy inhibitor chloroquine, a known antagonist of autophagy, counteracted the antiproliferation effect of BEZ235. Thus, our study indicates that autophagy induced in response to BEZ235 treatment appears to act as cell death mechanism in HCT15 CRC cells.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.597-601
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• 2016

Background: Components of the systemic inflammatory response, combined to form inflammation-based prognostic scores (mGPS, NLR, PLR, PI, PNI) have been associated with overall survival. The aim of the present study was to compare various prognostic factors including many previously established parameters and such systemic inflammation-based prognostic scores in a series of incurable stage IV colorectal cancer (CRC) patients. Materials and Methods: Patients (n=167) with stage IV CRC undergoing surgical procedures between 2005 and 2013 were enrolled. Preoperatively (7-30 days before surgery), routine laboratory examinations were performed on the same day. We calculated scores using these data and analyzed the association with cancer specific survival (CSS) statistically. Results: Univariate analysis revealed significant associations between CSS and WBC, albumin, CRP, CEA values, mGPS, PNI, and PI values among preoperative factors. On multivariate analysis, high mGPS and high CEA independently predicted shorter CSS (p=0.001 and p=0.018). A new scoring system was constructed using mGPS and CEA. When patients were separated into three categorized using this system, the new score accurately predicted CSS (p < 0.001). Conclusions: The present study indicates that a new scoring system, consisting of mGPS and CEA, is a simple and useful tool in predicting the survival of patients with incurable stage IV CRC, and should be included in the routine assessment of these patients for decision making of appropriate treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.9015-9019
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• 2014

The study aimed to compare the 2 main types of insurance used by colorectal cancer (CRC) patients in a university hospital in Thailand: universal coverage (UC) and 'Civil Servant Medical Benefit Scheme' (CSMBS) in terms of hospital expenditure and survival outcomes. CRC cases in stages I-IV who were operated on and had completed their adjuvant therapy in Songklanagarind Hospital from 2004 through 2013 were retrospectively reviewed regarding their hospital expenditure, focusing on surgical and chemotherapy costs. Of 1,013 cases analyzed, 524 (51.7%) were in the UC group while 489 (48.3%) belonged to the CSMBS group. Cases with stage IV disease were significantly more frequent in the UC group. Average total treatment expenditure (TTE) was 143,780 Thai Baht (THB) (1 US$ =~ 30 THB). The TTE increased with tumor stage and the chemotherapy cost contributed the most to the TTE increment. TTE in the CSMBS group was significantly higher than in the UC group for stage II-III CRCs. The majority of cases in the UC group (65.5%) used deGramont or Mayo as their first line regimen, and the proportion of cases who started with a capecitabine-based regimen (XELOX or $Xeloda^{(R)}$) was significantly higher in the CSMBS group (61.0% compared to 24.5% in the UC group, p-value < 0.01). On survival analysis, overall survival (OS) and progress free survival in the CSMBS group were significantly better than in the UC group. The 5-year OS in the CSMBS and UC groups were 84.3% and 74.6%, respectively (p-value < 0.01). In conclusion, the study indicates that in Thailand, the type of insurance influences resource utilization, especially the choice of chemotherapy, in CRC cases. This disparity in treatment, in turn, results in a gap in treatment outcomes.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.927-930
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• 2012

Background and Objectives: Artificial neural networks (ANNs) are flexible and nonlinear models which can be used by clinical oncologists in medical research as decision making tools. This study aimed to predict distant metastasis (DM) of colorectal cancer (CRC) patients using an ANN model. Methods: The data of this study were gathered from 1219 registered CRC patients at the Research Center for Gastroenterology and Liver Disease of Shahid Beheshti University of Medical Sciences, Tehran, Iran (January 2002 and October 2007). For prediction of DM in CRC patients, neural network (NN) and logistic regression (LR) models were used. Then, the concordance index (C index) and the area under receiver operating characteristic curve (AUROC) were used for comparison of neural network and logistic regression models. Data analysis was performed with R 2.14.1 software. Results: The C indices of ANN and LR models for colon cancer data were calculated to be 0.812 and 0.779, respectively. Based on testing dataset, the AUROC for ANN and LR models were 0.82 and 0.77, respectively. This means that the accuracy of ANN prediction was better than for LR prediction. Conclusion: The ANN model is a suitable method for predicting DM and in that case is suggested as a good classifier that usefulness to treatment goals.

• Molecules and Cells
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• 제41권5호
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• pp.423-435
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• 2018

This investigation was aimed at working out the combined role of lncRNA H19, miR-29b and Wnt signaling in the development of colorectal cancer (CRC). In the aggregate, 185 CRC tissues and corresponding para-carcinoma tissues were gathered. The human CRC cell lines (i.e. HT29, HCT116, SW480 and SW620) and normal colorectal mucosa cell line (NCM460) were also purchased. Si-H19, si-NC, miR-29b-3p mimics, miR-29b-3p inhibitor, si-PGRN and negative control (NC) were, respectively, transfected into the CRC cells. Luciferase reporter plasmids were prepared to evaluate the transduction activity of $Wnt/{\beta}-catenin$ signaling pathway, and dual-luciferase reporter gene assay was arranged to confirm the targeted relationship between H19 and miR-29b-3p, as well as between miR-29b-3p and PGRN. Finally, the proliferative and invasive capacities of CRC cells were appraised through transwell, MTT and scratch assays. As a result, overexpressed H19 and down-expressed miR-29b-3p displayed close associations with the CRC patients' poor prognosis (P < 0.05). Besides, transfection with si-H19, miR-29b-3p mimic or si-PGRN were correlated with elevated E-cadherin expression, decreased snail and vimentin expressions, as well as less-motivated cell proliferation and cell metastasis (P < 0.05). Moreover, H19 was verified to directly target miR-29b-3p based on the luciferase reporter gene assay (P < 0.05), and miR-29b-3p also bound to PGRN in a direct manner (P < 0.05). Finally, addition of LiCl ($Wnt/{\beta}-catenin$ pathway activator) or XAV93920 ($Wnt/{\beta}-catenin$ pathway inhibitor) would cause remarkably altered E-cadherin, c-Myc, vimentin and snail expressions, as well as significantly changed transcriptional activity of ${\beta}-catenin/Tcf$ reporter plasmid (P < 0.05). In conclusion, the lncRNA H19/miR-29b-3p/PGRN/Wnt axis counted a great deal for seeking appropriate diagnostic biomarkers and treatment targets for CRC.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6027-6032
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• 2015

Background: Polymorphisms of genes encoding PSCA, PLCE1 and MUC1 have been associated with the risk of different cancers in genome wide association studies (GWAS). Up to date there are limited data on the role of these genetic alterations in colorectal cancer (CRC) development. The aim of this study was to evaluate potential associations between single nucleotide polymorphisms (SNPs) of genes encoding PSCA, PLCE1 and MUC1 and the presence of CRC in European populations. Materials and Methods: Gene polymorphisms were analyzed in 574 European subjects (controls: n=382; CRC: n=192). PSCA C>T (rs2294008), PSCA G>A (rs2976392), MUC1 A>G (rs4072037) and PLCE1 A>G (rs2274223) SNPs were genotyped by RT-PCR. Results: The distribution of genotypes for all four SNPs was in line with the Hardy-Weinberg equilibrium (rs2294008, P=0.153; rs2976392, P=0.269; rs4072037, P=0.609; rs2274223, P=0.858). The distribution of genotypes and alleles of PSCA C>T, PSCA G>A, MUC1 A>G and PLCE1 A>G SNPs was similar among controls and CRC patient groups (P>0.05). GG genotype of MUC1 SNP was more frequent in CRC patients (24.0%) than in controls (20.2%); however, this association failed to reach significance (OR-1.45, P=0.15). Overall, in the present study SNPs of PSCA (rs2294008, rs2976392), MUC1 (rs4072037) and PLCE1 (rs2274223) genes were not associated with the presence of CRC. Conclusions: Gene polymorphisms of PSCA, PLCE1 and MUC1 genes are not associated with the presence of CRC in European subjects.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7223-7228
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• 2014

The MYH11 gene may be related to cell migration and adhesion, intracellular transport, and signal transduction. However, its relationship with prognosis is still uncertain. The aim of this study was to investigate correlations between MYH11 gene expression and prognosis in 58 patients with stage II and III colorectal cancer. Quantitative real-time polymerase chain reaction was performed in fresh CRC tissues to examine mRNA expression, and immunohistochemistry was performed with paraffin-embedded specimens for protein expression. On univariate analysis, MYH11 expression at both mRNA and protein levels, perineural invasion and lymphovascular invasion were related to disease-free survival (p<0.05; log-rank test). Cancers with lower MYH11 expression were more likely to have a poor prognosis. Otherwise, MYH11 expression was unrelated to patient clinicopathological features. On multivariate analysis, low MYH11 expression proved to be an independent adverse prognosticator (p<0.05). These findings show that MYH11 can contribute to predicting prognosis in stage II and III colorectal cancers.

• 문화기술의 융합
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• 제6권4호
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• pp.621-626
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• 2020

한국의 대장암 발병율은 점차 증가하고 있으며 대장암 발생은 식생활과 밀접하게 연관이 있는 것으로 보고되고 있다. 대장암 발생에 영향을 미칠 수 있는 식생활 태도 및 영양적 위험요인을 연구하기 위해 대구·경북지역에 거주하는 최근 1년 이내에 대장직장암으로 진단받은 환자 34명과 소화기계 질환이 없는 대조군 51명을 대상으로 식생활태도 및 반정량적 식품섭취빈도조사를 통한 영양섭취상태를 비교 분석하였다. 그 결과, 식사의 규칙성 및 식품섭취의 다양성은 대조군이 대장직장암 환자에 비해 높았으며 대장암 환자는 동식물성 단백질 섭취와 튀긴 음식, 그리고 녹황색 채소 및 과일류의 섭취가 대조군에 비해 높게 나타났다. 영양섭취분석에서는 대장직장암 환자가 대조군에 비해 비타민 A, E, K, C, 나트륨, 마그네슘, 요오드, 콜레스테롤의 섭취량이 유의적으로 높았으며 그 중 비타민 K와 나트륨 섭취는 대장직장암 발생의 위험요인으로 분석되었다. 향후 보다 많은 수의 연구대상자들을 통한 임상연구를 통하여 이들 영양소와 대장직장암 발생과의 상관관계를 확인하고 적절한 영양 교육을 시행한다면 대장직장암 발생의 위험을 예방하는데 도움이 될 것으로 사료된다.