Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer

2021 ◽  
Author(s):  
Xiao-Cheng Wang ◽  
Ya Liu ◽  
Fei-Wu Long ◽  
Liang-Ren Liu ◽  
Chuan-Wen Fan
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Markers ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Free Survival ◽  
Cancer Genome Atlas ◽  
Bioinformatic Approaches ◽  
Cell Phenotypes ◽  
The Relationship

Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

scholarly journals Identification of novel alternative splicing isoform biomarkers and their association with overall survival in colorectal cancer

2019 ◽  
Author(s):  
Hongtao Jia ◽  
Aili Wang ◽  
Haifeng Lian ◽  
Yuanyuan Shen ◽  
Qian Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Alternative Splicing ◽  
Cancer Biology ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Eukaryotic Gene ◽  
Cancer Genome Atlas ◽  
Alternative Splicing Events ◽  
Therapeutic Tools

Abstract Alternative splicing is an important mechanism of regulating eukaryotic gene expression. Understanding the most common alternative splicing events in colorectal cancer (CRC) will help developing diagnostic, prognostic or therapeutic tools in CRC. Publicly available RNA-seq data of 31 pairs of CRC and normal tissues and 18 pairs of metastatic and normal tissues were used to identify alternative splicing events using PSI and DEXSeq methods. The highly significant splicing events were used to search a database of The Cancer Genome Atlas (TCGA). We identified alternative splicing events in 10 genes marking the signature of CRC (more inclusion of CLK1-E4, COL6A3-E6, CD44v8-10, alternative first exon regulation of ARHGEF9, CHEK1, HKDC1 and HNF4A) or metastasis (decrease of SERPINA1-E1a, CALD-E5b, E6 and FBLN2-E9). Except for CHEK1, all other 9 splicing events were confirmed by TCGA data with 382 CRC tumors and 52 normal controls. Two splicing events (COL6A3 and HKDC1) were found to be significantly associated with patient overall survival. The alternative splicing signatures of the 10 genes are highly consistent with previous reports and/or relevant to cancer biology. The significant association of higher expression of the COL6A3 E5-E6 junction and HKDC1 E1-E2 with better overall survival was firstly reported. This study might be of significant value in the future biomarker, prognosis marker and therapeutics development of CRC.

scholarly journals Survival Outcomes by TP53 Mutation Status in Metastatic Breast Cancer

2018 ◽  
pp. 1-15 ◽  
Author(s):  
Funda Meric-Bernstam ◽  
Xiaofeng Zheng ◽  
Maryam Shariati ◽  
Senthil Damodaran ◽  
Chetna Wathoo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast ◽  
The Cancer Genome Atlas ◽  
Survival Outcomes ◽  
Tumor Subtype ◽  
Free Survival ◽  
Tp53 Mutations ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Purpose To determine the significant genomic alterations in patients with metastatic breast cancer (MBC) and survival outcomes in common genotypes. Patients and Methods High-depth next-generation sequencing was performed for 202 genes in tumor and normal DNA from 257 patients with MBC, including 165 with estrogen receptor/progesterone receptor–positive and human epidermal growth factor receptor 2 (HER2 [hormone receptor positive (HR+)])–positive, 32 with HER2-positive, and 60 with triple-negative (estrogen receptor/progesterone receptor–negative and HER2-negative) disease. Kaplan-Meier survival analysis was performed in the discovery set, in patients with breast cancer analyzed in The Cancer Genome Atlas, and in a separate cohort of 98 patients with MBC who underwent clinical genomic testing. Results Significantly mutated genes (SMGs) varied by histology and tumor subtype, but TP53 was an SMG in all three subtypes. The most SMGs in patients with HR+ cancer were PIK3CA (32%), TP53 (29%), GATA3 (15%), CDH1 (8%), MAP3K1 (8%), PTEN (5%), TGFBR2 (4%), AKT1 (4%), and MAP2K4 (4%). TP53 mutations were associated with shorter recurrence-free survival ( P = .004), progression-free survival ( P < .001), and overall survival ( P = .003). Furthermore, TP53 status was prognostic among patients with HR+ cancer with PIK3CA mutations. TP53 mutations were associated with poorer overall survival in the 442 patients with HR+ breast cancer analyzed in The Cancer Genome Atlas ( P = .042) and in an independent set of 96 patients with HR+ MBC who underwent clinical sequencing ( P < .001). Conclusion SMGs differ by tumor subtype, but TP53 is significantly mutated in all three breast cancer subtypes. TP53 mutations are associated with poor prognosis in HR+ breast cancer and should be considered in the design and interpretation of precision oncology trials.

High preoperative levels of circulating SFRP5 predict better prognosis in colorectal cancer patients

2020 ◽  
Vol 16 (31) ◽  
pp. 2499-2509
Author(s):  
Chandra Kirana ◽  
Eric Smith ◽  
Doan T Ngo ◽  
Markus I Trochsler ◽  
Peter J Hewett ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Normal Mucosa ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Cancer Genome Atlas ◽  
Colorectal Cancer Patients ◽  
Diagnostic And Prognostic Value

The purpose of this research was to investigate the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC). We evaluated preoperative cSFRP5 levels in CRC patients and controls (n = 208). We found significantly higher cSFRP5 levels in CRC patients compared with non-CRC controls (p < 0.001). Levels of cSFRP5 were significantly lower in CRC patients with either vascular invasion (p = 0.001) or liver metastasis (p = 0.016). High cSFRP5 levels were associated with longer disease-free survival in both univariate (p = 0.024) and multivariate (p = 0.015) analyses. Analysis of an independent tissue cohort from The Cancer Genome Atlas database revealed significantly lower SFRP5 RNA expression in CRC tumor tissue compared with adjacent normal mucosa (n = 590 vs 47; p < 0.0001). Our findings confirm the role of cSFRP5 as a physiologic tumor suppressor and demonstrate its potential diagnostic and prognostic value in CRC.

scholarly journals Identification of lnc RNAs Related to Prognosis of Patients With Colorectal Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382096212
Author(s):  
Yuqi Sun ◽  
Peng Peng ◽  
Lanlan He ◽  
Xueren Gao
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Cox Regression Analysis ◽  
Cancer Genome Atlas ◽  
Score Model ◽  
Prognostic Prediction

The purpose of this study was to identify long noncoding RNAs (lncRNAs) related to prognosis of patients with colorectal cancer (CRC) and develop a prognostic prediction model for CRC. Transcriptome data and survival information of CRC patients were downloaded from The Cancer Genome Atlas. The differentially expressed lncRNAs (DElncRNAs) between CRC and normal colorectal tissues were identified by the edgeR package. The association of DElncRNAs expression with prognosis of CRC patients was analyzed by the survival package. A nomogram predicting 3- and 5- year overall survival of CRC patients was drawn by the rms package. A total of 1046 DElncRNAs were identified, including 271 down-regulated and 775 up-regulated lncRNAs in CRC. Multivariate Cox regression analysis showed 10 lncRNAs related to the prognosis of CRC patients. Thereinto high expression of AC004009.1, LHX1-DT, ELFN1-AS1, AL136307.1, AC087379.2, RBAKDN and AC078820.1 was associated with poorer prognosis of CRC patients. High expression of LINC01055, AL590483.1 and AC008514.1 was associated with better prognosis of CRC patients. Furthermore, the risk score model developed based on the 10 lncRNAs could effectively predict overall survival of CRC patients. In conclusion, 10 prognostic biomarkers for CRC were identified, which would be helpful to understand the role of lncRNAs in CRC progression.

scholarly journals Editing and Expression of miR-589-5p as an Important Biomarker in Colorectal Cancer

2020 ◽  
Author(s):  
Yuanyi Yue ◽  
Qiang Zhang ◽  
Li Xiao
Keyword(s):  
Colorectal Cancer ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Expression Levels ◽  
The Third ◽  
Common Cancer ◽  
Cancer Genome Atlas ◽  
The Relationship ◽  
Mirna Editing ◽  
Editing Level

Abstract Objectives: Colorectal cancer (CRC) is recognized as the third most common cancer worldwide. Recently, emerging evidence showed that microRNA (miRNA) A-to-I editing plays crucial roles in cancer prognosis as well as cancer therapy. However, the relationship between CRC and miRNA editing remains not fully understood. Herein, we presented the first comprehensive analysis of miRNA editing events in CRC. Methods: Using patient data from The Cancer Genome Atlas (TCGA), we performed editing events and detected the expression levels of miR-589-5p. Results: we identified both editing events and the expression levels of miR-589-5p are significantly associated with Consensus Molecular Subtyping (CMS), especially for CMS4. The editing and expression levels of miR-589-5p impact almost completely different sets of gene expression, indicating the edited miR-589-5p plays a different role in CRC progression, compared to the wildtype miR-589-5p. Conclusions: In conclusion, our study provided the first association of miRNA editing and CRC. We demonstrated that expression and editing level of miR‑589‑5p may work as a novel biomarker for both prognosis and diagnosis in CRC.

scholarly journals Identification of novel alternative splicing isoform biomarkers and their association with overall survival in colorectal cancer

2019 ◽  
Author(s):  
Haifeng Lian ◽  
Aili Wang ◽  
Yuanyuan Shen ◽  
Qian Wang ◽  
Zhenru Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Alternative Splicing ◽  
Cancer Biology ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Eukaryotic Gene ◽  
Cancer Genome Atlas ◽  
Alternative Splicing Events ◽  
Therapeutic Tools

Abstract Alternative splicing is an important mechanism of regulating eukaryotic gene expression. Understanding the most common alternative splicing events in colorectal cancer (CRC) will help developing diagnostic, prognostic or therapeutic tools in CRC. Publicly available RNA-seq data of 31 pairs of CRC and normal tissues and 18 pairs of metastatic and normal tissues were used to identify alternative splicing events using PSI and DEXSeq methods. The highly significant splicing events were used to search a database of The Cancer Genome Atlas (TCGA). We identified alternative splicing events in 10 genes marking the signature of CRC (more inclusion of CLK1-E4, COL6A3-E6, CD44v8-10, alternative first exon regulation of ARHGEF9, CHEK1, HKDC1 and HNF4A) or metastasis (decrease of SERPINA1-E1a, CALD-E5b, E6 and FBLN2-E9). Except for CHEK1, all other 9 splicing events were confirmed by TCGA data with 382 CRC tumors and 52 normal controls. Two splicing events (COL6A3 and HKDC1) were found to be significantly associated with patient overall survival. The alternative splicing signatures of the 10 genes are highly consistent with previous reports and/or relevant to cancer biology. The significant association of higher expression of the COL6A3 E5-E6 junction and HKDC1 E1-E2 with better overall survival was firstly reported. This study might be of significant value in the future biomarker, prognosis marker and therapeutics development of CRC.

20q amplification defined by genomic and clinical characteristics as a subgroup with increased prevalence and better survival in metastatic colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16003-e16003
Author(s):  
Satish Maharaj ◽  
RuoBing Xue ◽  
Anmol Cheema
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Information Exchange ◽  
Clinical Characteristics ◽  
The Cancer Genome Atlas ◽  
Independent Prognostic Marker ◽  
Cancer Genome Atlas ◽  
Microsatellite Stability ◽  
Next Generation Sequencing Ngs

e16003 Background: Genomic instability from 20q amplification is an oncogenic pathway in colorectal cancer (CRC). Several genes have been implicated, including BCL2L1, AURKA, SRC, ASXL1, GNAS and TOP1. There is a lack of data regarding 20q amplified group and one study implicating these genes suggested these patients have better overall survival. Next Generation Sequencing (NGS) has become widely used in metastatic CRC (mCRC) and easily identifies patients with 20q amplification. Nevertheless, most oncologists do not routinely consider 20q amplification status and this subgroup remains underinvestigated. This study aims to investigate genomic and clinical characteristics of 20q amplified mCRC using a single-center retrospective cohort and a multi-center genomic dataset. Methods: A cohort was identified comprising patients with mCRC who had NGS testing of tumor DNA and were treated between 2014-2019. Cases with and without 20q amplification were identified. Genomic, clinical and survival data were analyzed. Significant genomic findings were compared with all-stage CRC data using the AACR Genomic Evidence Neoplasia Information Exchange (GENIE) and The Cancer Genome Atlas (TCGA) databases. Results: Of the mCRC cohort ( n= 72), 15% ( n= 11) had 20q amplification. Amplified and non-amplified groups had no significant differences in age, sex or follow-up time. Patients with 20q amplification were more likely to have never smoked, and less likely to have treatment with targeted therapy. Survival analysis showed clear separation with longer overall survival for the amplified group. Eight genes at loci 20q11 to 20q13 were amplified - in order of frequency: ASXL1, GNAS, ARFRP1, ZNF217, AURKA, BCL2L1, SRC and TOP1. 20q amplification was significantly associated with wild-type RAS and BRAF, microsatellite stability, mutant TP53 and mutant APC. Using the GENIE and TCGA databases, it was found that metastatic disease had increased prevalence of all 20q amplified genes except TOP1, when compared to all-stage CRC. Conclusions: Clinical use of NGS identifies the 20q amplification subgroup that has increased prevalence in mCRC (compared to all CRC). Compared to non-20q amplified mCRC, this group had better survival, suggesting genomic pattern in mCRC is a novel independent prognostic marker. We believe mCRC patients would benefit from further studies defining a genomic prognostication model and development of therapy targeting the 20q amplification pathway.

scholarly journals Identification of novel alternative splicing isoform biomarkers and their association with overall survival in colorectal cancer

2020 ◽  
Author(s):  
Haifeng Lian ◽  
Aili Wang ◽  
Yuanyuan Shen ◽  
Qian Wang ◽  
Zhenru Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Alternative Splicing ◽  
Cancer Biology ◽  
The Cancer Genome Atlas ◽  
Sample Type ◽  
Normal Tissues ◽  
Eukaryotic Gene ◽  
Cancer Genome Atlas ◽  
Therapeutic Tools

Abstract Background: Alternative splicing (AS) is an important mechanism of regulating eukaryotic gene expression. Understanding the most common AS events in colorectal cancer (CRC) will help developing diagnostic, prognostic or therapeutic tools in CRC.Methods: Publicly available RNA-seq data of 28 pairs of CRC and normal tissues and 18 pairs of metastatic and normal tissues were used to identify AS events using PSI and DEXSeq methods. Result: The highly significant splicing events were used to search a database of The Cancer Genome Atlas (TCGA). We identified AS events in 9 genes in CRC (more inclusion of CLK1-E4, COL6A3-E6, CD44v8-10, alternative first exon regulation of ARHGEF9, CHEK1, HKDC1 and HNF4A) or metastasis (decrease of SERPINA1-E1a, CALD-E5b, E6). Except for CHEK1, all other 8 splicing events were confirmed by TCGA data with 382 CRC tumors and 51 normal controls. The combination of three splicing events was used to build a logistic regression model that can predict sample type (CRC or normal) with near perfect performance (AUC=1). Two splicing events (COL6A3 and HKDC1) were found to be significantly associated with patient overall survival. The AS features of the 9 genes are highly consistent with previous reports and/or relevant to cancer biology. Conclusions: The significant association of higher expression of the COL6A3 E5-E6 junction and HKDC1 E1-E2 with better overall survival was firstly reported. This study might be of significant value in the future biomarker, prognosis marker and therapeutics development of CRC.

VARIANTS OF METABOLIC SYNDROME OF THE PATIENTS WITH COLORECTAL CANCER: A RELATIONSHIP WITH CLINICAL AND MORPHOLOGICAL PARAMETERS

2019 ◽  
Vol 65 (6) ◽  
pp. 863-867
Author(s):  
Anastasiya Dimcha ◽  
Natalya Yunusova ◽  
Sergey Afanasev ◽  
Yelena Zambalova
Keyword(s):  
Colorectal Cancer ◽  
Metabolic Syndrome ◽  
Overall Survival ◽  
International Diabetes Federation ◽  
Statistical Processing ◽  
Tumor Grade ◽  
Free Survival ◽  
Diabetes Mellitus Type Ii ◽  
Waist Size ◽  
The Relationship

The objective is to study the incidence of metabolic syndrome (MS) and overweight in patients with colorectal cancer as well as to evaluate the relationship with clinical and morphological features and to analyze the incidence of 3-, 4- and 5- components МS in patients with colorectal cancer. Materials and methods. The investigation involved 99 people with the prevalence of the tumor process T2-3N1-2M1. Depending on the presence of MS or overweight patients were divided into 3 groups. The recommendations of the International Diabetes Federation (2005) were used for inclusion in the group with MS. Statistical processing of the results was made with the Statistica 10.0 software package. Results. About 78% of patients with colorectal cancer had metabolic disorders: 67% had MS, 11% had overweight. The patients with colorectal cancer had mainly the 3- and 4-components variants of MS (46% and 47%, respectively), the 5 components MS occurred in 7% of cases. No significant relationship was found between the presence/absence of the MS, and MS variant and age, sex, stage, and localization of the tumor process. A significant correlation was revealed between the presence of MS/ MS variants and tumor Grade. In particular, G3 adenocarcinomas meet more often in the presence of MS5. An association of MS and its individual components was identified with recurrence- free / overall survival, in particular, the presence of MS, an increase in body mass index, waist size, and the presence of diabetes mellitus type II is associated with a decrease in recurrence-free survival. Increased blood triglyceride levels are associated with a decrease in overall survival.

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