Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study

Abstract Background Colorectal cancer (CRC) is a malignancy of the large intestine, whose development and prognosis have been demonstrated to be associated with altered lipid metabolism. High cholesterol intake is associated with an increased risk of CRC, and elevated serum cholesterol levels are known to be correlated with risk of developing CRC. Niemann-Pick C1-Like 1 (NPC1L1), a target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, whether the altered expression of NPC1L1 affects CRC development and prognosis is currently unknown. Methods Data corresponding to patients with CRC were obtained from The Cancer Genome Atlas (TCAG). Datasets from the Genome Data Analysis Center (GDAC) platform were analyzed to compare the expression of NPC1L1 in normal and CRC tissues using the Mann–Whitney U test and chi-square test. Further, the datasets from the Gene Expression Omnibus (GEO) database were analyzed. The log-rank test and multivariate Cox proportional hazard regression analysis were performed to determine whether NPC1L1 significantly affects the prognosis of CRC. Results The expression of NPC1L1 was found to be upregulated in CRC and was significantly associated with the N and pathological stages but not with the histological type, age, and sex. Increased NPC1L1 expression in CRC was related to poor patient survival, as evidenced by the Kaplan–Meier and multivariate regression analyses. Conclusions As high expression of NPC1L1 was associated with CRC development, pathological stage, and prognosis, NPC1L1 can serve as an independent prognostic marker for CRC.

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Expression and Prognostic Significance of NPC1L1 in Colorectal Cancer: A Retrospective Cohort Study

10.21203/rs.3.rs-614918/v1 ◽

2021 ◽

Author(s):

Ryuk Jun Kwon ◽

Soo Min Son ◽

Eun Ju Park ◽

Sang Yeoup Lee ◽

Jungin Choi ◽

...

Keyword(s):

Colorectal Cancer ◽

Proportional Hazards ◽

Prognostic Significance ◽

Gene Expression Omnibus ◽

Cox Proportional Hazards ◽

The Cancer Genome Atlas ◽

Rank Test ◽

Chi Square ◽

Independent Prognostic Marker ◽

Niemann Pick

Abstract Background: Colorectal cancer (CRC) is a malignant tumor of the large intestine. Studies have shown that the development and prognosis of CRC are associated with altered lipid metabolism. Niemann-Pick C1-Like 1 (NPC1L1), the target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, the role of altered NPC1L1 expression in the development and prognosis of CRC has not yet been determined.Methods: Datasets of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) database. To compare the expression of NPC1L1 in normal and CRC tissues, datasets obtained from the GDAC platform were used. To support these results, we also analyzed other datasets from the Gene Expression Omnibus (GEO) database. Student’s t-test and chi-square test were used for the analyses. The log-rank test and multivariate Cox proportional hazards regression analysis were performed to determine whether NPC1L1 is a significant factor affecting the prognosis of CRC.Results: The mRNA expression of NPC1L1 was found to be upregulated in CRC, and was significantly associated with the N- and pathological stages, but not with the histological type, age, and sex. Moreover, an increase in NPC1L1 expression in CRC was associated with poorer survival, based on the Kaplan–Meier and multivariate regression analyses.Conclusions: High expression of NPC1L1 is associated with CRC development, pathological stage, and prognosis. The present study suggests that NPC1L1 represents a potential independent prognostic marker for CRC.

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Implications of Habitual Alcohol Intake With the Prognostic Significance of Mean Corpuscular Volume in Stage II-III Colorectal Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.681406 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qi Liu ◽

Yufei Yang ◽

Xinxiang Li ◽

Sheng Zhang

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Mean Corpuscular Volume ◽

Alcohol Intake ◽

Prognostic Significance ◽

Stage Ii ◽

Rank Test ◽

Corpuscular Volume ◽

Prognostic Role ◽

Increased Risk

ObjectiveTo elucidate the prognostic significance of mean corpuscular volume (MCV), with implications of habitual alcohol intake in stage II-III colorectal cancer (CRC).BackgroundMCV had the potential to become an ideal prognostic biomarker and be put into clinical application. Few studies, however, have explored whether habitual alcohol intake which greatly increased the value of MCV would affect the prognostic role of MCV.MethodsEligible patients were identified from the CRC database of Fudan University Shanghai Cancer Center (FUSCC) between January 2012 and December 2013. Survival analyses were constructed using the Kaplan–Meier method to evaluate the survival time distribution, and the log-rank test was used to determine the survival differences. Univariate and multivariate Cox proportional hazard models were built to calculate the hazard ratios of different prognostic factors.ResultsA total of 694 patients diagnosed with stage II-III CRC between January 2012 and December 2013 were identified from FUSCC. Low pretreatment MCV was independently associated with 72.0% increased risk of overall mortality compared with normal MCV (HR = 1.720, 95%CI =1.028-2.876, P =0.039, using normal MCV as the reference). In patients with habitual alcohol intake, however, pretreatment MCV positively correlated with the mortality (P = 0.02) and tumor recurrence (P = 0.002) after adjusting for other known prognostic factors.ConclusionsIn CRC patients without habitual alcohol intake, low (<80 fL) level of pretreatment MCV was a predictor of poor prognosis. In patients with habitual alcohol intake, however, pretreatment MCV showed the opposite prognostic role, which would elicit many fundamental studies to elucidate the mechanisms behind.

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Identification of Genes in Patients for Predicting Ulcerative Colitis-Associated Colorectal Cancer

10.21203/rs.3.rs-24097/v1 ◽

2020 ◽

Author(s):

hongyun wei ◽

qian zhang ◽

xiaosa chi ◽

xiaohui yang ◽

zibin tian ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Ulcerative Colitis ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Rank Test ◽

Hub Genes ◽

Protein Protein Interaction ◽

Limma Package ◽

Public Datasets

Abstract BackgroundUlcerative colitis (UC) has been considered as a risk factor for colorectal cancer (CRC). However, effective biomarkers for predicting UC-associated CRC are lacking. Therefore, it is necessary to screen biomarkers associated with UC-related CRC, which could be used to evaluate UC-associated CRC early, and provide possible mechanisms involved in UC-associated CRC. Efficient bioinformatics analysis could help us to explore potential biomarkers.MethodsTwo public datasets, including 44 UC without CRC samples and 17 UC-associated CRC samples were chosen from Gene Expression Omnibus (GEO) database. Sva package was used to remove batch effects, and then we screened out differentially expressed genes (DEGs) with limma package. STRING and Cytoscape were used to achieve protein-protein interaction (PPI) network analysis. The survival curves between high and low gene expression were performed by log rank test based on the cancer genome atlas (TCGA) program. The expression of three identified hub genes was validated based on Oncomine. To validate the expression of three hub genes, we compared the expression of three hub genes between normal and colorectal cancer based on Oncomine.Results405 DEGs were identified, including 256 down-regulated genes and 149 up-regulated genes in UC-associated CRC tissues. 16 hub genes were identified. And among them, RPL6, RPL7, and RPL35 were related to poor prognosis of patients in survival analysis. Higher expression of RPL6, RPL7, and RPL35 was validated in CRC tissues based on Oncomine.ConclusionsOur study showed that overexpressed RPL6, RPL7, and RPL 35 may be potential tumor oncogenes and could act as a prognostic factor in clinical diagnosis and treatment.

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Prognostic value of piR-39980 in patients with colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16087 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16087-e16087

Author(s):

Wei Peng ◽

Jingfeng Mei ◽

Jianwei Lu ◽

Jun Bao ◽

Guoren Zhou

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Value ◽

Cox Regression ◽

Survival Curve ◽

Prognostic Significance ◽

Rank Test ◽

Chi Square ◽

Log Rank Test ◽

Independent Indicator

e16087 Background: Colorectal cancer (CRC) accounts for a common gastrointestinal malignancy all over world. Piwi-interacting RNAs (piRNAs) show a substantial role in the oncogenesis of a variety of tumors. The objective of this work was to uncover the expression profile of piR-39980 and its prognostic value in CRC. Methods: The levels of piR-39980 expression in CRC tissues and paired normal tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Association of piR-39980 with CRC clinical feathers was assessed by Chi-square test. Overall survival curve was built via log-rank test by Kaplan–Meier analysis. The prognostic significance of piR-39980 in CRC was measured by Cox regression model. Results: piR-39980 was upregulated in CRC specimens than the paired normal specimens ( P < 0.001). Importantly, upregulation of piR-39980 was related to tumor size and T stage (all P < 0.05). Survival evaluation suggested that CRC folks with high expression of piR-39980 went through poorer overall survival than folks with low piR-39980 expression (log rank test, P = 0.0429). piR-39980 could be an independent indicator for CRC patients’ prognosis (HR = 3.308, 95% CI = 1.762-6.594, P = 0.043). Conclusions: piR-39980 plays oncogenic roles in CRC tumorigenesis and may be an independent indicator for CRC prognosis.

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The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

Scientific Reports ◽

10.1038/s41598-021-90220-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yu Zhang ◽

Zhaohui Zhong ◽

Mei Li ◽

Jingyi Chen ◽

Tingru Lin ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

The Cancer Genome Atlas ◽

Actin Dynamics ◽

Elevated Expression ◽

Sw480 Cells ◽

And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

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Methylation Status of Corticotropin-Releasing Factor (CRF) Receptor Genes in Colorectal Cancer

Journal of Clinical Medicine ◽

10.3390/jcm10122680 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2680

Author(s):

Maria Panagopoulou ◽

Antonia Cheretaki ◽

Makrina Karaglani ◽

Ioanna Balgkouranidou ◽

Eirini Biziota ◽

...

Keyword(s):

Colorectal Cancer ◽

In Silico ◽

Methylation Status ◽

Prognostic Significance ◽

In Silico Analysis ◽

Clinicopathological Characteristics ◽

Corticotropin Releasing Factor ◽

Altered Expression ◽

High Performing ◽

Methylation Patterns

The corticotropin-releasing factor (CRF) system has been strongly associated with gastrointestinal pathophysiology, including colorectal cancer (CRC). We previously showed that altered expression of CRF receptors (CRFRs) in the colon critically affects CRC progression and aggressiveness through regulation of colonic inflammation. Here, we aimed to assess the potential of CRFR methylation levels as putative biomarkers in CRC. In silico methylation analysis of CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2) was performed using methylome data derived by CRC and Crohn’s disease (CD) tissues and CRC-derived circulating cell-free DNAs (ccfDNAs). In total, 32 and 33 differentially methylated sites of CpGs (DMCs) emerged in CRFR1 and CRFR2, respectively, between healthy and diseased tissues. The methylation patterns were verified in patient-derived ccfDNA samples by qMSP and associated with clinicopathological characteristics. An automated machine learning (AutoML) technology was applied to ccfDNA samples for classification analysis. In silico analysis revealed increased methylation of both CRFRs in CRC tissue and ccfDNA-derived datasets. CRFR1 hypermethylation was also noticed in gene body DMCs of CD patients. CRFR1 hypermethylation was further validated in CRC adjuvant-derived ccfDNA samples, whereas CRFR1 hypomethylation, observed in metastasis-derived ccfDNAs, was correlated to disease aggressiveness and adverse prognostic characteristics. AutoML analysis based on CRFRs methylation status revealed a three-feature high-performing biosignature for CRC diagnosis with an estimated AUC of 0.929. Monitoring of CRFRs methylation-based signature in CRC tissues and ccfDNAs may be of high diagnostic and prognostic significance in CRC.

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Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

10.21203/rs.3.rs-471663/v1 ◽

2021 ◽

Author(s):

Yanghui Wen ◽

Hui Su ◽

Wuke Wang ◽

Feng Ren ◽

Haitao Jiang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Expression Profiles ◽

Prognostic Significance ◽

The Cancer Genome Atlas ◽

Clinicopathological Parameters ◽

Chi Square ◽

Kaplan Meier ◽

Chi Square Test ◽

Liver Hepatocellular Carcinoma ◽

The Relationship

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.

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CIP4 Expression is Associated With The Prognosis in Colorectal Cancer

10.21203/rs.3.rs-95046/v1 ◽

2020 ◽

Author(s):

Keqian Zhang ◽

Tianqi Mao ◽

Zhicheng He ◽

Xiaojiao Wu ◽

Yu Peng ◽

...

Keyword(s):

Colorectal Cancer ◽

Cox Regression ◽

Prognostic Significance ◽

Lymphatic Invasion ◽

Chi Square ◽

Interacting Protein ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Chi Square Test ◽

Student’S T

Abstract Background: This study was conducted to detect the expression of Cdc42 interacting protein 4 (CIP4) in patients with colorectal cancer (CRC), and explore the role of CIP4 in prognosis of CRC patients.Methods: The expression of CIP4 mRNA was determined by quantitative real-time PCR (qRT-CPR) and compared by student’s t-test between groups. Relationships of clinical characteristics and CIP4 expression were analyzed by Chi-square test. Kaplan-Meier curves were used to estimate the overall survival of CRC patients. And Cox regression analysis was conducted to identify the prognostic biomarkers for CRC patients.Results: The qRT-PCR results showed that CRC tissues were detected with significantly high CIP4 mRNA expression compared with adjacent normal controls (P<0.0001). The overexpression of CIP4 in CRC tissues was influenced by distant metastasis (P=0.021), lymphatic invasion (P=0.012) and TNM stage (P=0.006). But, other clinical factors including age, gender, differentiation and tumor site were proved to have no obvious effects on CIP4 expression (all, P>0.05). The survival curves showed that patients with high CIP4 expression generally lived shorter than those with low CIP4 expression (P<0.001). In addition, the multivariate analysis revealed that differentiation (P=0.044, HR=1.631, 95%CI=1.013-2.626) and CIP4 expression (P=0.000, HR=5.283, 95%CI=3.138-8.893) were of great prognostic significance for CRC patients.Conclusion: Taken together, up-regulation of CIP4 in CRC tissues represented poor prognosis for patients.

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Comprehensive Analysis of Expression, Clinicopathological Association and Potential Prognostic Significance of RABs in Pancreatic Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21155580 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5580 ◽

Cited By ~ 1

Author(s):

Shashi Anand ◽

Mohammad Aslam Khan ◽

Moh’d Khushman ◽

Santanu Dasgupta ◽

Seema Singh ◽

...

Keyword(s):

Prognostic Significance ◽

Small Gtpases ◽

The Cancer Genome Atlas ◽

Ductal Adenocarcinoma ◽

Diabetic Patients ◽

Rab Proteins ◽

Clear Trend ◽

Aberrant Expression ◽

Transport Pathways ◽

Altered Expression

RAB proteins (RABs) represent the largest subfamily of Ras-like small GTPases that regulate a wide variety of endosomal membrane transport pathways. Their aberrant expression has been demonstrated in various malignancies and implicated in pathogenesis. Using The Cancer Genome Atlas (TCGA) database, we analyzed the differential expression and clinicopathological association of RAB genes in pancreatic ductal adenocarcinoma (PDAC). Of the 62 RAB genes analyzed, five (RAB3A, RAB26, RAB25, RAB21, and RAB22A) exhibited statistically significant upregulation, while five (RAB6B, RAB8B, RABL2A, RABL2B, and RAB32) were downregulated in PDAC as compared to the normal pancreas. Racially disparate expression was also reported for RAB3A, RAB25, and RAB26. However, no clear trend of altered expression was observed with increasing stage and grade, age, and gender of the patients. PDAC from occasional drinkers had significantly higher expression of RAB21 compared to daily or weekly drinkers, whereas RAB25 expression was significantly higher in social drinkers, compared to occasional ones. The expression of RABL2A was significantly reduced in PDAC from diabetic patients, whereas RAB26 was significantly lower in pancreatitis patients. More importantly, a significant association of high expression of RAB21, RAB22A, and RAB25, and low expression of RAB6B, RABL2A, and RABL2B was observed with poorer survival of PC patients. Together, our study suggests potential diagnostic and prognostic significance of RABs in PDAC, warranting further investigations to define their functional and mechanistic significance.

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The Prediction and Prognostic Significance of INPP5K Expression in Patients with Liver Cancer

BioMed Research International ◽

10.1155/2020/9519235 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Ruobing Wang ◽

Yan Jiao ◽

Yanqing Li ◽

Siyang Ye ◽

Guoqiang Pan ◽

...

Keyword(s):

Liver Cancer ◽

Mrna Expression ◽

Poor Prognosis ◽

Prognostic Significance ◽

The Cancer Genome Atlas ◽

Inositol Polyphosphate ◽

Chi Square ◽

Cancer Genome Atlas ◽

Poor Outcomes ◽

The Relationship

Liver cancer is a devastating disease for humans with poor prognosis. Although the survival rate of patients with liver cancer has improved in the past decades, the recurrence and metastasis of liver cancer are still obstacles for us. Inositol polyphosphate-5-phosphatase K (INPP5K) belongs to the family of phosphoinositide 5-phosphatases (PI 5-phosphatases), which have been reported to be associated with cell migration, polarity, adhesion, and cell invasion, especially in cancers. However, there have been few studies on the correlation of INPP5K and liver cancer. In this study, we explored the prognostic significance of INPP5K in liver cancer through bioinformatics analysis of data collected from The Cancer Genome Atlas (TCGA) database. Chi-square and Fisher exact tests were used to evaluate the relationship between INPP5K expression and clinical characteristics. Our results showed that low INPP5K expression was correlated with poor outcomes in liver cancer patients. Univariate and multivariate Cox analyses demonstrated that low INPP5K mRNA expression played a significant role in shortening overall survival (OS) and relapse-free survival (RFS), which might serve as the useful biomarker and prognostic factor for liver cancer. In conclusion, low INPP5K mRNA expression is an independent risk factor for poor prognosis in liver cancer.

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