scholarly journals Construction of immune-related lncRNA signature to predict aggressiveness, immune landscape, and drug resistance of colorectal cancer

2021 ◽  
Author(s):  
Yonggan Xue ◽  
Bobin Ning ◽  
Hongyi Liu ◽  
Baoqing Jia
Keyword(s):  
Colorectal Cancer ◽  
Survival Data ◽  
Clinical Characteristics ◽  
Risk Model ◽  
Survival Outcomes ◽  
Lasso Regression ◽  
Differential Analysis ◽  
Operating Characteristics ◽  
Treatment Regimens ◽  
Hr Model

Abstract Background:Colorectal cancer (CRC) remains one of the most common malignancies across the world. Thus far, a biomarker, which can comprehensively predict the survival outcomes, clinical characteristics, and therapeutic sensitivity, is still lacking. Methods: We leveraged retrieved transcriptomic data of CRC from the public database, and constructed irlncRNA pairs. After integrating with clinical survival data, we performed differential analysis and constructed 11 irlncRNA pairs signature using Lasso regression analysis. We next drew the 1-, 5-, 10-year curve line of receiver operating characteristics, calculated the areas under the curve, and recognized the optimal cutoff point. Then, we validated the pair-risk model in terms of the survival outcomes of the patients. Moreover, we tested the reliability of the pair-risk model for predicting tumor aggressiveness and therapeutic responsiveness of CRC. Additionally, we reemployed the 11 of irlncRNAs involved in the pair-risk model to construct an expression risk model that was also highly predictive of prognostic outcomes of CRC patients. Results:We recognized a total of 377 DEirlcRNAs, including 28 low-expressed and 349 high-expressed irlncRNAs in CRC patients. After performing a univariant Cox analysis, we identified 115 risk irlncRNAs that were significantly correlated with survival outcomes of patients with CRC. By taking the intersection of the DEirlcRNAs and the risk irlncRNAs, we ultimately recognized 55 irlncRNA as core irlncRNAs. Then, we established a Cox HR model (pair-risk model) as well as an expression HR model (exp-risk model). We found that both of the two models significantly outperformed the common-used clinical characteristics, including age, T, N, and M stages, in terms of predicting survival outcomes. Moreover, we validated the pair-risk model can serve as a potential tool for studying the tumor microenvironment of CRC and drug response. Additionally, we noticed that combining the pair-risk model and exp-risk model yielded a more robust approach for predicting the survival outcomes of patients with CRC.Conclusions:We suggest that the irlncRNA-based risk models can be utilized as prognostic tools to predict survival outcomes and clinical characteristics and guide treatment regimens of CRC.

scholarly journals Construction of immune-related lncRNA signature to predict aggressiveness, immune landscape, and drug resistance of colorectal cancer

2021 ◽  
Author(s):  
Yonggan Xue ◽  
Bobin Ning ◽  
Hongyi Liu ◽  
Baoqing JIa
Keyword(s):  
Colorectal Cancer ◽  
Survival Data ◽  
Clinical Characteristics ◽  
Risk Model ◽  
Expression Patterns ◽  
Risk Groups ◽  
Survival Outcomes ◽  
Lasso Regression ◽  
Optimal Cutoff ◽  
Treatment Regimens

Abstract Background Colorectal cancer (CRC) remains one of the most common malignancies across the world, threatening almost millions of lives every year and increasingly adding the social-economical burden. Thus far, a biomarker, which can comprehensively predict the survival outcomes, clinical characteristics, and therapeutic sensitivity, is still lacking. Results This study established a pair-risk model, together with, an exp-risk model to predict biological characteristics of CRC based on immune-related lncRNA (irlncRNA) expression patterns. We retrieved transcriptomic data of CRC, including 473 tumor samples and 41 normal samples, and identified 739 irlncRNA through co-expression analysis, and constructed irlncRNA pairs. After integrating with clinical survival data, we established an 11 irlncRNA pairs signature using Lasso regression analysis. We next drew the 1-, 5-, 10-year curve line of receiver operating characteristic (ROC), calculated the areas under the curve (AUC), and recognized the optimal cutoff point. Patients with CRC were stratified into high- and low-risk groups based on the optimal cutoff value. Then, we validated the pair-risk model in terms of the survival outcomes of the patients. Moreover, we tested the reliability of the pair-risk model for predicting tumor aggressiveness and therapeutic responsiveness of CRC. Additionally, we reemployed the 11 of irlncRNAs involved in the pair-risk model to constructed an expression risk model that was also highly predictive of prognostic outcomes of CRC patients. Importantly, combining the pair-risk model and exp-risk model yielded a more robust approach for predicting the survival outcomes of patients with CRC. Conclusions We suggest that the irlncRNA-based risk models can be utilized as prognostic tools to predict survival outcomes and clinical characteristics and guide treatment regimens of CRC.

Immune Characteristics-Related Typing of Colorectal Cancer and the Establishment of 14-Gene Prognostic Model

2021 ◽  
Author(s):  
Jianxing Ma ◽  
Chen Wang
Keyword(s):  
Colorectal Cancer ◽  
Risk Model ◽  
Cox Regression ◽  
Nonnegative Matrix ◽  
Test Group ◽  
Progression Free Survival ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Immune Related Genes

Abstract This study is to establish NMF (nonnegative matrix factorization) typing related to the tumor microenvironment (TME) of colorectal cancer (CRC) and to construct a gene model related to prognosis to be able to more accurately estimate the prognosis of CRC patients. NMF algorithm was used to classify samples merged clinical data of differentially expressed genes (DEGs) of TCGA that are related to the TME shared in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, and survival differences between subtype groups were compared. By using createData Partition command, TCGA database samples were randomly divided into train group and test group. Then the univariate Cox analysis, Lasso regression and multivariate Cox regression models were used to obtain risk model formula, which is used to score the samples in the train group, test group and GEO database, and to divide the samples of each group into high-risk and low-risk groups, according to the median score of the train group. After that, the model was validated. Patients with CRC were divided into 2, 3, 5 subtypes respectively. The comparison of patients with overall survival (OS) and progression-free survival (PFS) showed that the method of typing with the rank set to 5 was the most statistically significant (p=0.007, p<0.001, respectively). Moreover, the model constructed containing 14 immune-related genes (PPARGC1A, CXCL11, PCOLCE2, GABRD, TRAF5, FOXD1, NXPH4, ALPK3, KCNJ11, NPR1, F2RL2, CD36, CCNF, DUSP14) can be used as an independent prognostic factor, which is superior to some previous models in terms of patient prognosis. The 5-type typing of CRC patients and the 14 immune-related genes model constructed by us can accurately estimate the prognosis of patients with CRC.

Somatic mutation landscape of appendiceal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 671-671 ◽  
Author(s):  
John P. Shen ◽  
Miriam T. Jacobs ◽  
Ingrid L Fuh ◽  
Joel Micah Baumgartner ◽  
Paul T. Fanta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Somatic Mutation ◽  
Survival Data ◽  
Randomized Clinical Trials ◽  
Clinical Investigation ◽  
Primary Objective ◽  
Lower Prevalence ◽  
Appendiceal Cancer ◽  
Treatment Regimens ◽  
Metastatic Setting

671 Background: Appendiceal cancers are rare, comprising just 0.5% of all intestinal neoplasia, which has prevented the systematic study of these tumors in randomized clinical trials. Given this absence of clinical data, no evidence-based guidelines exist regarding the best management of this disease. Standard treatment generally follows consensus guidelines for colorectal cancer; however, there are currently no standards to guide chemotherapy selection in the adjuvant or metastatic setting. Methods: Somatic mutation profiles covering ~300 frequently mutated genes were obtained for 385 primary appendiceal tumors (Foundation Medicine). A retrospective review was performed to gather clinico-pathologic data. The primary objective was to assess the somatic mutation profile of each subtype of appendiceal cancer and to compare these to colorectal cancer. Colorectal data was obtained from TCGA cohort via cBioPortal. Results: Appendiceal adenocarcinoma (non-mucinous) and mucinous adenocarcinoma had shared somatic mutations albeit with differing frequencies. The most common mutations were KRAS (60.1% and 80.5%, respectively), GNAS (32.4%, 58.5%), TP53 (42.8%, 19.5%), and SMAD4 (14.8%, 14.6%). Tumors with goblet cell (adenocarcinoid) histology had lower prevalence of KRAS (16.0%) and GNAS mutations (8.0%), but similar prevalence of TP53 mutation (24.0%) and a greater prevalence of ARID1A mutation (20.0%). The mutation profiles of all appendiceal histologies differed from colorectal adenocarcinoma with markedly lower prevalence of ATM (7.9% vs. 71.0%). Chemotherapy data was available for 30 metastatic patients; these patients received an average of 1.76 lines of therapy (range 1-4). All 30 were treated with either 5-FU or capecitabine, 11 (36.7%) with oxaliplatin, 23 (76.7%) with irinotecan and 19 (63.3%) with bevacizumab. Analysis of survival data and correlation with molecular and histologic features is ongoing. Conclusions: Despite clear molecular differences between appendiceal and colorectal tumors, appendiceal tumors are primarily treated with colorectal chemotherapy regimens. There remains a pressing need for both pre-clinical and clinical investigation to develop treatment regimens specific to appendix cancer.

Racial and socioeconomic disparities in overall survival in colorectal cancer (CRC) at West Cancer Center & Research Institute (WCCRI), Memphis, TN.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16122-e16122
Author(s):  
Vanessa Wookey ◽  
Gabriella Bufalino ◽  
Gregory A. Vidal ◽  
Bradley G. Somer ◽  
Lee S. Schwartzberg ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Private Insurance ◽  
Socioeconomic Disparities ◽  
Cancer Center ◽  
Survival Outcomes ◽  
Median Income ◽  
Entire Cohort ◽  
Stage 4

e16122 Background: WCCRI, a comprehensive regional community oncology center in Memphis, Tennessee and the Mid-South region, serves a racially, geographically and socioeconomically diverse patient cohort. We sought to evaluate disparity of outcomes in survival by race and socioeconomic status, in addition to patient and tumor characteristics. Methods: All consecutive patients referred to and treated at WCCRI with colorectal adenocarcinoma from 2007-2013 were included. Individual chart review was performed to verify diagnosis, stage, and date and cause of death. Kaplan-Meier Overall Survival curves were generated for the entire cohort and by race, sex, tumor location and income derived from zip code. WCCRI survival data were compared to SEER data. Results: From 2007-2013, 1,176 patients were included in the analysis: 405 blacks, 757 whites, 14 others. Median age at diagnosis: Blacks 58 yrs, whites 61 yrs. Stage distribution at diagnosis: stage 1: 100, stage 2: 275, stage 3: 425, stage 4: 376. All stages combined, blacks trended towards shorter OS vs whites (5-year OS: 52.8% vs 58.3%; median survival 71.0 mos vs 98.6 mos; p= 0.095). Blacks presented at later stages (71.4% at stage 3 or 4 vs 66.3% for whites) but no statistically significant OS differences were seen when compared by stage. Patients at or below the median income of $39,590 for WCC had worse 5-year OS (51.6% vs. 61.1%; p= 0.006), as did patients without private insurance (5-year OS: uninsured: 48.0%, Medicare/Medicaid: 50.0%, private: 62.0%; p< 0.001). Adjusted for stage, 5-year OS was statistically significant for stage 4 (private: 18.0%, Medicare/Medicaid: 9.4%, uninsured: 8.3%; p= 0.020). A higher proportion of blacks were below the median income (69% vs 39%) but no statistically significant OS differences were seen when adjusted by race. Overall, cancer survival outcomes were similar to SEER results. Conclusions: At WCCRI, black patients with CRC presented at a later stage than whites, however, adjusted for stage, no significant racial difference in OS was found. Income and insurance status influenced survival outcomes. Overall, our results reveal racial and socioeconomic disparities in colorectal cancer in a diverse US population and further detailed multivariate data analyses are underway.

Racial and socioeconomic disparities in overall survival in colorectal cancer (CRC) at West Cancer Center (WCC), Memphis, TN.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 80-80
Author(s):  
Vanessa Wookey ◽  
Gabriella Bufalino ◽  
Gregory A. Vidal ◽  
Bradley G. Somer ◽  
Lee S. Schwartzberg ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Private Insurance ◽  
Socioeconomic Disparities ◽  
Cancer Center ◽  
Survival Outcomes ◽  
Median Income ◽  
Entire Cohort ◽  
Stage 4

80 Background: WCC, a comprehensive regional community oncology center in Memphis, Tennessee and the Mid-South region, serves a racially, geographically and socioeconomically diverse patient cohort. We sought to evaluate disparity of outcomes in survival by race and socioeconomic status, in addition to patient and tumor characteristics. Methods: All consecutive patients referred to and treated at WCC with colorectal adenocarcinoma from 2007-2013 were included. Individual chart review was performed to verify diagnosis, stage, and date and cause of death. Kaplan-Meier Overall Survival curves were generated for the entire cohort and by race, sex, tumor location and income derived from zip code. WCC survival data were compared to SEER data. Results: From 2007-2013, 1,176 patients were included in the analysis: 405 blacks, 757 whites, 14 others. Median age at diagnosis: Blacks 58 yrs, whites 61 yrs. Stage distribution at diagnosis: stage 1: 100, stage 2: 275, stage 3: 425, stage 4: 376. All stages combined, blacks trended towards shorter OS vs whites (5-year OS: 52.8% vs 58.3%; median survival 71.0 mos vs 98.6 mos; p= 0.095). Blacks presented at later stages (71.4% at stage 3 or 4 vs 66.3% for whites) but no statistically significant OS differences were seen when compared by stage. Patients at or below the median income of $39,590 for WCC had worse 5-year OS (51.6% vs. 61.1%; p= 0.006), as did patients without private insurance (5-year OS: uninsured: 48.0%, Medicare/Medicaid: 50.0%, private: 62.0%; p< 0.001). Adjusted for stage, 5-year OS was statistically significant for stage 4 (private: 18.0%, Medicare/Medicaid: 9.4%, uninsured: 8.3%; p= 0.020). A higher proportion of blacks were below the median income (69% vs 39%) but no statistically significant OS differences were seen when adjusted by race. Overall, cancer survival outcomes were similar to SEER results. Conclusions: At WCC, black patients with CRC presented at a later stage than whites, however, adjusted for stage, no significant racial difference in OS was found. Income and insurance status affected survival outcomes. Overall, our results reveal racial and socioeconomic disparities in colorectal cancer in a diverse US population.

Amphiregulin and Epiregulin mRNA Expression in Primary Tumors Predicts Outcome in Metastatic Colorectal Cancer Treated With Cetuximab

2009 ◽  
Vol 27 (30) ◽  
pp. 5068-5074 ◽  
Author(s):  
Bart Jacobs ◽  
Wendy De Roock ◽  
Hubert Piessevaux ◽  
Robin Van Oirbeek ◽  
Bart Biesmans ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Survival Data ◽  
Kras Mutation ◽  
Odds Ratio ◽  
Cox Regression ◽  
Objective Response ◽  
Operating Characteristics ◽  
Primary Tumors ◽  
Ligand Expression

PurposeTo study the power of the epidermal growth factor receptor (EGFR) epiregulin (EREG) and amphiregulin (AREG) ligands' expression in primary tumors to predict the outcome in patients with chemorefractory metastatic colorectal cancer (cmCRC) treated with the combination of cetuximab and irinotecan.Patients and MethodsGene expression measurements and KRAS mutation analysis were performed on archival formalin-fixed paraffin-embedded primary tumors of 220 cmCRC patients. Response was measured using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. The relation between ligand expression levels and outcome was evaluated using logistic regression for response and Cox regression for survival data. Receiver operating characteristics analysis was performed for response and survival data. CIs for the performance indices were obtained with a nonparametric bootstrap procedure. Findings were externally validated on a series of 67 samples treated in a similar setting.ResultsIn KRAS wild type (WT) patients, there was a significant association between log-transformed ligand expression and response for EREG (odds ratio for objective response, 1.90; 95% CI, 1.27 to 2.83; P = .0005; concordance index [c-index], 0.681) and for AREG (odds ratio for objective response, 1.862; 95% CI, 1.22 to 2.72; P = .0017; c-index, 0.673). In a Cox regression model, dichotomized ligand expression was significantly associated with progression-free survival (PFS) and overall survival (OS). EREG PFS hazard ratio (HR) was 0.41 (95% CI, 0.274 to 0.609; P < .001; time-dependent c-index [Cτ index], 0.640), and AREG PFS HR was 0.43 (95% CI, 0.29 to 0.64; P < .001; Cτ index, 0.627). EREG OS HR was 0.42 (95% CI, 0.28 to 0.63; P < .0001; Cτ index, 0.639), and AREG OS HR was 0.40 (95% CI, 0.27 to 0.64; P < .0001; Cτ index, 0.625). There was no predictive power of ligand expression in patients with KRAS mutation.ConclusionExpression of EGFR ligands in primary tumors significantly predicts outcome in KRAS WT cmCRC treated with cetuximab and irinotecan.

scholarly journals A New Prognostic and Therapeutic Immune-related Risk Signature of Colorectal Cancer

2021 ◽  
Author(s):  
Yuan Li ◽  
Hao Huang ◽  
Jun Feng ◽  
Yulan Zhu ◽  
Tianwei Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regression Analysis ◽  
Risk Model ◽  
Cox Regression ◽  
R Package ◽  
Lasso Regression ◽  
Cox Regression Analysis ◽  
Related Risk ◽  
Set Up ◽  
Microsatellite Stability

Abstract BackgroundAlthough some advanced colorectal cancer (CRC) patients could select immunotherapy, but still most microsatellite stability (MSS) CRC patients did not respond. Our present study aims to set up a novel system for prognostic prediction and immunotherapeutic responsiveness for MSS CRC patients.MethodsUnivariable Cox regression survival analysis and least absolute shrinkage and selector operation (LASSO) regression analysis were performed to identify prognostic genes and establish immune risk signatures. Multivariate Cox regression analysis was performed to verify whether these clinical features could predict prognosis. R package was used to analyze the relationship between the immune-related risk model and these immune cells, effector molecules, and immune checkpoints.ResultsWe constructed an immune-related signature and verified its predictive capability. Immune-related signature included 12 differentially expressed IRGs (12 DE IR MSSGs), including CXCL1, CD36, FABP4, MS4A2, NRG1, VGF, GRP, HDC, XCL1, NGF, MAGEA1, and IL13. The signature consisting of 12 DE IR MSSGs was an independent and effective prognostic factor for the overall survival of CRC patients. In addition, the signature consisting of 12 DE IR MSSGs reflected the infiltration characteristics of different immunocytes in tumor immune microenvironment. The signature consisting of 12 DE IR MSSGs also had a significant correlation with immune checkpoint molecules.

scholarly journals Identification of Hub Genes for Controlling Cancer Stem Cell Characteristics in Colorectal Cancer by Bioinformatics Analysis

2021 ◽  
Author(s):  
Xiang Li ◽  
Shuoyang Huang ◽  
Chao Yang ◽  
Yongbin Zheng
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Survival Data ◽  
Prognostic Model ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Immune Microenvironment ◽  
Hub Genes ◽  
Normal Tissues ◽  
Cancer Genome Atlas

Abstract Background Cancer stem cells (CSCs), which are capable of infinite proliferation and self-renewal, play a crucial role in the occurrence and development of colorectal cancer (CRC). The study of the expression characteristics of CRC stem cell-related genes and their interaction with the immune microenvironment may contribute to CRC treatment. Results In order to explore the hub genes that regulate the stemness characteristics of CRC, we obtained gene expression values of the Cancer Genome Atlas (TCGA), stemness indices (mRNAsi), and corresponding survival data from UCSC Xena Browser. Differentially expressed genes (DEGs) were identified in cancer and normal tissues. Then we screened 2 modules and 210 mRNAsi-related genes from 4,941 DEGs by weighted gene co-expression network analysis. A prognostic model including ten genes (VCAN, SPARC, COL12A1, THBS2, COL1A2, COL5A1, TAGLN, DCN, MYH11, CDH11) was constructed using protein interaction networks and LASSO regression. We also evaluated the relationship between cancer stemness and immune response and found there was a strong correlation between each other. Conclusions Our study establishes a prognostic model associated with CSCs and reveals the association between mRNAsi and the tumor immune microenvironment, which is useful for the targeted therapy of CRC.

scholarly journals Identification of an RNA-Binding-Protein-Based Prognostic Model for Ewing Sarcoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3736
Author(s):  
Yi Chen ◽  
Huafang Su ◽  
Yanhong Su ◽  
Yifan Zhang ◽  
Yingbo Lin ◽  
...  
Keyword(s):  
Ewing Sarcoma ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Risk Model ◽  
Rna Binding Proteins ◽  
Lasso Regression ◽  
Operating Characteristics ◽  
Clinical Prognosis ◽  
Kaplan Meier ◽  
Patient Prognosis

RNA-binding proteins (RBPs) are important transcriptomic regulators and may be important in tumorigenesis. Here, we sought to investigate the clinical impact of RBPs for patients with Ewing sarcoma (ES). ES transcriptome signatures were characterized from four previously published cohorts and grouped into new training and validation cohorts. A total of three distinct subtypes were identified and compared for differences in patient prognosis and RBP signatures. Next, univariate Cox and Lasso regression models were used to identify hub prognosis-related RBPs and construct a prognostic risk model, and prediction capacity was assessed through time-dependent receiver operating characteristics (ROCs), Kaplan–Meier curves, and nomograms. Across the three RBP subtypes, 29 significant prognostic-associated RBP genes were identified, of which 10 were used to build and validate an RBP-associated prognostic risk model (RPRM) that had a stable predictive value and could be considered valuable for clinical risk-stratification of ES. A comparison with immunohistochemistry validation showed a significant association between overall survival and NSUN7 immunoreactivity, which was an independent favorable prognostic marker. The association of RBP signatures with ES clinical prognosis provides a strong rationale for further investigation into RBPs molecular mechanisms.

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.

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