MC1R Is a Prognostic Marker and Its Expression Is Correlated with MSI in Colorectal Cancer

Melanocortin 1 receptor (MC1R) is thought to be a marker of poor prognosis and a potential target for the treatment of melanoma. Studies have found that MC1R promotes several tumor behaviors, including cell proliferation and differentiation, pigment formation, and genome damage repair. Some single-nucleotide polymorphisms (SNPs) of MC1R are involved in the occurrence and development of melanoma. A few studies have reported a relationship between MC1R and colorectal cancer (CRC). In this research, our objective was to examine MC1R expression and MC1R SNPs and investigate their correlation with the clinicopathological features of human CRC tissues. We evaluated MC1R mRNA expression by performing bioinformatic analyses on human CRC expression datasets. We used Western blotting and RT-qPCR to compare MC1R expression in CRC tissues with that in normal tissues, and MC1R SNPs in CRC tissues were detected by PCR-direct sequencing (DS). The expression of MC1R was significantly decreased in CRC tissues compared with normal tissue, and its expression was negatively associated with P53 expression, MLH1 expression, and PMS2 expression, and high MC1R expression was significantly associated with microsatellite instability (MSI). MC1R SNPs were also associated with the clinicopathological characteristics of CRC; for example, the rs2228479 locus genotype was correlated with Ki67 status, and the rs885479 locus genotype was correlated with age and T stage. In conclusion, MC1R plays a crucial role in the progression of CRC and may be a marker of poor prognosis in CRC.

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The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Chemotherapy ◽

10.1159/000519913 ◽

2022 ◽

pp. 1-10

Author(s):

Cheng Yang ◽

Na Xie ◽

Zhifei Luo ◽

Xiling Ruan ◽

Yixin Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Protein Expression ◽

Poor Prognosis ◽

Cancer Metastasis ◽

Mrna Level ◽

Normal Mucosa ◽

Tnm Stage ◽

Expression Levels ◽

Normal Tissues

Introduction: We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). Methods: CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. Results: Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. Conclusion: CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

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A Functional Polymorphism in the Promoter Region of Interleukin-12B Increases the Risk of Colorectal Cancer

BioMed Research International ◽

10.1155/2020/2091781 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Yabin Liu ◽

Binghui Li ◽

Lili Wang ◽

Dexian Kong

Keyword(s):

Colorectal Cancer ◽

Direct Sequencing ◽

Transcriptional Level ◽

Mrna Levels ◽

Normal Tissues ◽

Sequencing Method ◽

Direct Sequencing Method ◽

Healthy Control ◽

Polymerase Chain ◽

Interleukin 12B

Objective. To investigate whether the polymorphisms of interleukin-12B (IL-12B) were associated with the risk of developing colorectal cancer (CRC). Patients and Methods. Genotypes of rs17860508 and rs3212227 were determined by polymerase chain reaction with a direct sequencing method in 329 CRC patients and 342 matched healthy control subjects. The expression of IL-12B mRNA was determined by RT-qPCR in 50 pairs of CRC tissues and their adjacent normal tissues. Results. Compared with TTAGAG/TTAGAG genotype of rs17860508, the GC/GC and TTAGAG/GC genotypes may significantly increase the risk of CRC (OR = 1.81, 95% CI = 1.18–2.78; OR = 1.46, 95% CI = 1.01–2.12, respectively). Furthermore, the mRNA levels of IL-12B were significantly higher in the CRC tissues from patients with the rs17860508 GC/GC genotype than those with the TTAGAG/GC (P=0.009) and TTAGAG/TTAGAG (P=0.001) genotypes. Conclusion. These data suggested that the rs17860508 GC/GC genotype might upregulate IL-12B expression at the transcriptional level and thus increase the risk of CRC.

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Gene polymorphisms of CCL3, CCL4, CCL5, and CCR5 network in metastatic colorectal cancer patients treated with regorafenib.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.199 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 199-199

Author(s):

Mitsukuni Suenaga ◽

Wu Zhang ◽

Tetsuo Mashima ◽

Marta Schirripa ◽

Shu Cao ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Gene Polymorphisms ◽

Direct Sequencing ◽

Rank Test ◽

Alternative Mechanism ◽

Nucleotide Polymorphisms ◽

Positive Correlation ◽

Colorectal Cancer Patients

199 Background: We previously reported that genetic variant in the CCL5/CCR5 pathway predict efficacy of regorafenib in metastatic colorectal cancer patients (mCRC). CCL5 rs2280789 G allele and CCL5 rs3817655 T allele were associated with longer overall survival (OS) and severe skin toxicity due to low VEGF-A production via endothelial progenitor cell (EPC). CCL4 rs1634517 G allele and CCL3 rs1130371 C allele correlated with longer Progression-free survival (PFS) and OS. We investigated the biological role of CCL4 and CCL3 gene polymorphisms. Methods: We analyzed genomic DNA extracted from 79 samples of a Japanese cohort receiving regorafenib. Single nucleotide polymorphisms (SNPs) of genes in CCL5/CCR5 pathway were analyzed by PCR-based direct sequencing. Blood samples were obtained from 57 patients at baseline (BL), day 21 and progressive disease (PD), and serum CCR5, CCR5 ligands (CCL3, CCL4, CCL5) and VEGF-A levels were measured using ELISA. PFS and OS were analyzed using Kaplan-Meier curves and log-rank test. Results: Increased CCL3 levels at PD were associated with longer OS than decreased (12.6 vs 4.8 mos, P = 0.003). Patients with decreased CCL4 levels at day 21 had a trend toward longer PFS and tumor shrinkage. Positive correlation was observed between CCL3 and CCR5 throughout the treatment independent of other ligands (change at day 21: r = 0.426, P = 0.009). There was no significant correlation of CCL3 and CCL4 levels with VEGF-A levels. Patients with the G/G variant in CCL3 rs1130371 had increased CCL3, CCR5 and CCL5 levels at day 21 than any A allele. Similarly, patients with the C/C variant had increased CCL3, CCR5 and CCL5 levels at day 21 compared with those with any A allele. In contrast, both CCL5 rs2280789 G allele and CCL5 rs3817655 T allele were associated with increased CCL3 levels and decreased CCL4 levels at day 21 (P = 0.006, P = 0.043; P = 0.006, P = 0.043). Conclusions: Positive correlation of CCL3, CCR5 and CCL5 impact similarly on CCL3 and CCL4 SNPs, while different manner between CCL3 and CCL4 was found in CCL5 SNPs. This suggests an alternative mechanism of action in the network of CCR5 and the ligands except CCL5-VEGF-A signaling via EPC in mCRC patients receiving regorafenib.

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Predictive Value of Clinical Toxicities to Chemotherapy with Fluoropyrimidines and Oxaliplatin in Colorectal Cancer by DPYD and GSTP1 Genes Polymorphisms

10.21203/rs.3.rs-73108/v1 ◽

2020 ◽

Author(s):

Xunwei Deng ◽

Jingyuan Hou ◽

Qiaoting Deng ◽

Zhixiong Zhong

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Direct Sequencing ◽

Dihydropyrimidine Dehydrogenase ◽

Severe Neutropenia ◽

Severe Toxicity ◽

Nucleotide Polymorphisms ◽

Significant Difference ◽

Grade 3 ◽

Colorectal Cancer Patients

Abstract Background: Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to Chemotherapy-related adverse events. The present study was aimed to determine the role of DPYD and GSTP1 variants on patient chemotherapy toxicity risk among the Hakka population, minimize adverse events and in order to maximize therapy outcome for individualized treatment.Methods: Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drugs based chemotherapy regimen by direct sequencing of DPYD and GSTP1 polymorphisms. Three DPYD variants including *2A, *5A, *9A and GSTP1 c.313A>G were analyzed and clinical outcomes were assessed. Results: The data suggest that the incidence of DPYD*5A, DPYD*9A and GSTP1 c.313A>G variants were 37.5%, 24% and 31.7%, respectively. DPYD*2A variant was not found. A total of 38 patients (36.5%) suffered severe neutropenia and 23 patients (22.1%) suffered severe vomiting. DPYD*5A polymorphism was found significantly associated with grade 3/4 ulceration (p = 0.001). GSTP1 was determined to be an independent risk factor for severe neutropenia and ulceration (p = 0.010 and p = 0.034, respectively). Patients with GSTP1 c.313A>G wild type contributed to higher risk for grade severe toxicity compared with A/G + G/G genotype (p = 0.024). However, there was no significant difference between patients with DPYD*9A T/T and T/C + C/C genotype for chemotherapeutic toxicity.Conclusions: The results demonstrated that DPYD*5A and GSTP1 polymorphisms were useful predictors for severe events. Screening of single nucleotide polymorphisms of DPYD and GSTP1 in colorectal cancer patients prior to chemotherapy may help to realize personalized therapy.

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EYA4 could be an indicator signifying colorectal cancer sufferers' prognoses

10.21203/rs.3.rs-46920/v1 ◽

2020 ◽

Author(s):

Yang Yan ◽

Xiaohui Du ◽

Shaoyou Xia ◽

Songyan Li ◽

Da Teng ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cox Regression ◽

Survival Curve ◽

Mrna Level ◽

Clinicopathological Characteristics ◽

Rank Test ◽

Normal Tissues ◽

Log Rank Test ◽

Low Expression

Abstract Background Eyes absent 4 (EYA4) is involved in various biological processes. The aim of this study was to investigate the expression of EYA4 and its prognostic value in colorectal cancer (CRC). Methods The mRNA level of EYA4 in diseased tissues and adjacent normal tissues of CRC patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The association between EYA4 expression and clinicopathological characteristics was analyzed by χ2 test. Kaplan-Meier analysis with log rank test was performed to evaluate the effects of EYA4 expression on overall survival of CRC patients. Cox regression model was applied for prognosis analysis in CRC. Results The mRNA level of EYA4 was significantly decreased in CRC tissues compared with that in the adjacent normal tissue (P < 0.01). And its expression was affected by DUKE stage (P = 0.034), differentiation (P = 0.027) and vascular invasion (P = 0.037). Survival curve showed that patients with low expression of EYA4 had a significantly shorter overall survival than those with high expression (log rank test, P = 0.008). Low expression of EYA4 (HR = 1.989, 95%CI = 1.090-3.62902, P = 0.025) was an independent biomarker for poor prognosis in CRC patients. Conclusion EYA4 expression is decreased in CRC patients and negatively correlated with aggressive tumor progression. EYA4 may be a potential prognostic biomarker for CRC.

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Expression Profiling of Calcium Channels and Calcium-Activated Potassium Channels in Colorectal Cancer

Cancers ◽

10.3390/cancers11040561 ◽

2019 ◽

Vol 11 (4) ◽

pp. 561 ◽

Cited By ~ 15

Author(s):

Ibrahim ◽

Dakik ◽

Vandier ◽

Chautard ◽

Paintaud ◽

...

Keyword(s):

Colorectal Cancer ◽

Potassium Channels ◽

Poor Prognosis ◽

The Cancer Genome Atlas ◽

Normal Tissues ◽

Calcium Sensors ◽

Kca Channels ◽

Cancer Genome Atlas ◽

Calcium Activated Potassium Channels ◽

Ca2 Channels

Background: Colorectal cancer (CRC) is a highly devastating cancer. Ca2+-dependent channels are now considered key regulators of tumor progression. In this study, we aimed to investigate the association of non-voltage gated Ca2+ channels and Ca2+-dependent potassium channels (KCa) with CRC using the transcriptional profile of their genes. Methods: We selected a total of 35 genes covering KCa channels KCNN1–4, KCNMA1 and their subunits KCNMB1–4, endoplasmic reticulum (ER) calcium sensors STIM1 and STIM2, Ca2+ channels ORAI1–3 and the family of cation channels TRP (TRPC1–7, TRPA1, TRPV1/2,4–6 and TRPM1–8). We analyzed their expression in two public CRC datasets from The Cancer Genome Atlas (TCGA) and GSE39582. Results: KCNN4 and TRPM2 were induced while KCNMA1 and TRPM6 were downregulated in tumor tissues comparing to normal tissues. In proximal tumors, STIM2 and KCNN2 were upregulated while ORAI2 and TRPM6 were downregulated. ORAI1 decreased in lymph node metastatic tumors. TRPC1 and ORAI3 predicted poor prognosis in CRC patients. Moreover, we found that ORAI3/ORAI1 ratio is increased in CRC progression and predicted poor prognosis. Conclusions: KCa and Ca2+ channels could be important contributors to CRC initiation and progression. Our results provide new insights on KCa and Ca2+ channels remodeling in CRC.

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TRIB3 promotes hepatocellular carcinoma growth and predicts poor prognosis

Cancer Biomarkers ◽

10.3233/cbm-201577 ◽

2020 ◽

Vol 29 (3) ◽

pp. 307-315

Author(s):

Xiao-Jun Wang ◽

Fei-Fei Li ◽

Yi-Jing Zhang ◽

Man Jiang ◽

Wan-Hua Ren

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Xenograft Model ◽

Clinicopathological Characteristics ◽

Tissue Samples ◽

Normal Tissues ◽

Related Family ◽

Hcc Cells

BACKGROUND: Tribbles pseudokinase 3 (TRIB3) is a member of the tribbles-related family, which is involved a lot of cellular processes and multiple cancers, such as breast cancer, colorectal cancer, renal cell carcinomas, and lung cancer. However, the expression pattern and biological function of TRIB3 in hepatocellular carcinoma (HCC) has not yet been completely elucidated. METHODS: The expression of TRIB3 and clinicopathological characteristics were evaluated by HCC tissue microarray and qPCR analysis. Lentivirus packaging and transfection were employed to establish cell lines with TRIB3 overexpression or knockdown. The biological functions of TRIB3 in the growth of HCC were determined using MTT and crystal violet assays. Tumor growth was monitored in a xenograft model in vivo. RESULTS: The expression of TRIB3 was upregulated in HCC tissue samples compared to paired normal tissues in 45 patients examined by qPCR assay. TRIB3 expression was significantly correlated with HCC tumor size and prognosis in postoperative patients by analysis of the TRIB3 expression data and HCC clinical features. Forced expression of TRIB3 significantly promoted HCC growth in vitro. In contrast, downregulation of TRIB3 inhibited cell growth in vitro. Moreover, knockdown of TRIB3 suppressed tumorigenesis of HCC cells in vivo. CONCLUSION: TRIB3 promotes growth abilities of HCC cells both in vitro and in vivo and predicts poor prognosis of HCC patients, which serves as a prognostic marker and might provide a potential therapeutic candidate for patients with HCC.

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Dysregulation of CCL18/CCR8 axis predicts poor prognosis in patients with gastric cancer

European Journal of Inflammation ◽

10.1177/2058739218796887 ◽

2018 ◽

Vol 16 ◽

pp. 205873921879688

Author(s):

Jie Yi ◽

Shao-Jie Jiang

Keyword(s):

Gastric Cancer ◽

Poor Prognosis ◽

Tumor Recurrence ◽

Pearson Correlation ◽

Clinicopathological Characteristics ◽

Sequencing Data ◽

Normal Tissues ◽

Cox Proportional Hazard ◽

Chemokine Ligand ◽

Cox Proportional Hazard Regression

Increasing data have shown that the dysregulation of C-C motif chemokine ligand 18 (CCL18) and C-C motif chemokine receptor (CCR8) is involved in the development and progression of multiple malignancies. However, the clinical significance of CCL18/CCR8 axis in gastric cancer (GC) was still undocumented. In this study, the expression levels of CCL18 and its receptor CCR8 and their correlation with the clinicopathological characteristics and prognosis in patients with GC were analyzed by TCGA RNA sequencing data. Cox proportional hazard regression model was performed to assess the association between CCL18/CCR8 expression and overall survival (OS) and tumor recurrence in patients with GC. As a consequence, we found that the expression of CCL18 was markedly elevated in GC samples as compared with the adjacent normal tissues and acted as an independent prognostic factor of tumor recurrence in patients with GC. Subsequently, Pearson correlation analysis revealed that CCL18 possessed a positive correlation with CCR8 expression in GC samples. CCR8 expression was upregulated in GC tissues and exhibited the association with poor survival in patients with GC. Taken together, our findings demonstrated that the dysregulation of CCL18/CCR8 axis could predict the poor prognosis in patients with GC and provide a potential antitumor target for the treatment of GC.

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An Elevated Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Colorectal Cancer: A Meta-Analysis

Disease Markers ◽

10.1155/2017/1053125 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 15

Author(s):

Xuan-zhang Huang ◽

Wen-jun Chen ◽

Xi Zhang ◽

Cong-cong Wu ◽

Chao-ying Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Poor Prognosis ◽

Meta Analysis ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

Platelet To Lymphocyte Ratio ◽

Poor Overall Survival ◽

Cancer Specific Survival ◽

Free Survival ◽

Lymphocyte Ratio

Background.The aims of this study were to evaluate the clinicopathological and prognostic values of platelet-to-lymphocyte ratio (PLR) in colorectal cancer (CRC).Methods.The PubMed and Embase databases and the references of relevant studies were systematically searched. This study was performed with hazard ratios (HRs) and odd ratios (ORs) with corresponding 95% confidence intervals (CIs) as effect measures.Results.Our results indicated that elevated PLR was associated with poor overall survival (HR = 1.46, 95% CI = 1.23–1.73), disease-free survival (HR = 1.64, 95% CI = 1.17–2.30), cancer-specific survival (HR = 1.30, 95% CI = 1.12–1.51), and recurrence-free survival (HR = 1.38, 95% CI = 1.09–1.74) in CRC. For the clinicopathological characteristics, our results indicated that there were differences in the rate of elevated PLR between stages III/IV and I/II groups (OR = 1.38, 95% CI = 1.01–1.88), pT3/T4 and pT1/T2 groups (OR = 1.82, 95% CI = 1.03–3.20), and poor differentiation and moderate/well differentiation (OR = 2.59, 95% CI = 1.38–4.84).Conclusions.Our results indicated that elevated PLR predicted poor prognosis and clinicopathological characteristics in CRC and PLR is a convenient and low-cost blood-derived prognostic marker for CRC.

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Down-regulation of miRNA-30c predicts poor prognosis in Colorectal Cancer patients

Revista Romana de Medicina de Laborator ◽

10.1515/rrlm-2016-0037 ◽

2016 ◽

Vol 24 (4) ◽

pp. 369-375

Author(s):

Liu Bin ◽

Meng Zhang ◽

Liu Lixia ◽

Zang Aimin ◽

Yang Hua ◽

...

Keyword(s):

Colorectal Cancer ◽

Poor Prognosis ◽

Univariate Analysis ◽

Clinicopathological Features ◽

Expression Level ◽

Rt Pcr ◽

Normal Tissues ◽

Node Metastasis ◽

Treatment Measures ◽

Colorectal Cancer Patients

Abstract Background: MiRNA-30c was a tumor suppressor in several human cancers, however, its association with clinicopathological features and prognosis in colorectal cancer (CRC) is unclear. Materials and Methods: The expression level of miRNA-30c in 192 pairs of colorectal cancer and adjacent normal tissues was detected by Quantitative RT-PCR, the association between miRNA-30c expression and clinical characteristics and prognosis were statistically analyzed. Results: miRNA-30c was significantly lower in CRC tissues specimens compared with matched normal adjacent tissue (P<0.001). MiRNA-30c was positively correlated with tumor size (P=0.012), TMN stage (P=0.002) and lymph node metastasis (P=0.004). The univariate analysis showed CRC patients with low miRNA-30c had distinctly shorter overall survival (P<0.001) than patients with high miRNA-30c expression level. The multivariate analysis was performed and informed that low miRNA-30c expression (P<0.001) might be an independent prognostic predictor for poor prognosis. Conclusion: miRNA-30c could predict the prognosis of colorectal cancer which is helpful to choose reasonable treatment measures.

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