Background Colorectal cancer(CRC)is a complex,heterogeneous disease characterized by frequent relapses and metastasis.Previous studies have reported that the invasion and progression of CRC in several cases can be con...Background Colorectal cancer(CRC)is a complex,heterogeneous disease characterized by frequent relapses and metastasis.Previous studies have reported that the invasion and progression of CRC in several cases can be controlled by targeting fusion genes.This study aimed to screen for potent fusion transcripts as potential molecular biomarkers and therapeutic targets for metastatic CRC(mCRC)using an in silico approach.Methods RNA sequencing(RNA-seq)data from 18 patients with primary CRC and matched normal and mCRC samples were derived from the same patient set.Novel fusion transcripts were screened using the Kallisto and Pizzly software,followed by Gene Ontology(GO),pathway analysis,transcription factor enrichment,and survival for functional enrichment analysis.Furthermore,the fusion transcripts’utility as biomarkers was evaluated using a pan-cancer analysis.Results In total,32 fusion genes unique to mCRC were identified.Hub gene analysis identified 17 novel fusion transcripts,and GO analysis revealed that these genes were enriched in different biological and molecular functions.Pathways significantly correlated with CRC included the complement and coagulation cascades,ferroptosis,interleukin-17(IL-17)signaling pathway,and estrogen signaling pathway.We identified albumin-eukaryotic translation elongation factor 1 alpha 1(ALB-EEF1A1)as unique to mCRC based on significant gene expression and survival outcomes.Moreover,its utility as a prognostic biomarker was confirmed using a pan-cancer analysis.Conclusions ALB-EEF1A1 may play a pivotal role in the metastatic transformation of primary CRC and significantly increase the risk of death.The identified ALB-EEF1A1 fusion transcripts are promising novel molecular targets that may serve as prognostic and diagnostic biomarkers and treatment targets for mCRC in the future.展开更多
Molecular subtypes-based therapies offer new potential framework for desired and precise outcome in clinical settings.Current treatment strategies in colorectal cancer are largely‘one drug fit all’model for patients...Molecular subtypes-based therapies offer new potential framework for desired and precise outcome in clinical settings.Current treatment strategies in colorectal cancer are largely‘one drug fit all’model for patients that display same pathological conditions.However,CRC is a very heterogenous set ofmalignancy that does not support for above criteria.Each subtype displays different pathological and genetic signatures.Based on these features,therapeutic stratification for individual patients may be designed,which may ultimately lead to improved therapeutic outcomes.In this comprehensive review,we have attempted to briefly outline major CRC pathways.A detailed overview of molecular subtypes and their clinical significance has been discussed.Present and futuremethods,governing CRC subtyping in the era of personalized therapywith a special emphasis on CMS subtypes of CRC has been reviewed.Together,discovery and validation of new CRC patient stratification methods,screening for novel therapeutic targets,and enhanced diagnosis of CRC may improve the treatment outcome.展开更多
Colorectal cancer(CRC)is known to harbor considerable heterogeneity.1 Consequently,it could be hypothesized that similar-appearing tumors might exhibit substantial genetic differences while diverse-appearing tumors ma...Colorectal cancer(CRC)is known to harbor considerable heterogeneity.1 Consequently,it could be hypothesized that similar-appearing tumors might exhibit substantial genetic differences while diverse-appearing tumors may have a similar genetic landscape.2 Due to these differences at the molecular level,they behave or respond differently to therapies as well.CRC progression is a multistep process and involves the accumulation of substantial genetic and epigenetic events in a stage-dependent manner.展开更多
文摘Background Colorectal cancer(CRC)is a complex,heterogeneous disease characterized by frequent relapses and metastasis.Previous studies have reported that the invasion and progression of CRC in several cases can be controlled by targeting fusion genes.This study aimed to screen for potent fusion transcripts as potential molecular biomarkers and therapeutic targets for metastatic CRC(mCRC)using an in silico approach.Methods RNA sequencing(RNA-seq)data from 18 patients with primary CRC and matched normal and mCRC samples were derived from the same patient set.Novel fusion transcripts were screened using the Kallisto and Pizzly software,followed by Gene Ontology(GO),pathway analysis,transcription factor enrichment,and survival for functional enrichment analysis.Furthermore,the fusion transcripts’utility as biomarkers was evaluated using a pan-cancer analysis.Results In total,32 fusion genes unique to mCRC were identified.Hub gene analysis identified 17 novel fusion transcripts,and GO analysis revealed that these genes were enriched in different biological and molecular functions.Pathways significantly correlated with CRC included the complement and coagulation cascades,ferroptosis,interleukin-17(IL-17)signaling pathway,and estrogen signaling pathway.We identified albumin-eukaryotic translation elongation factor 1 alpha 1(ALB-EEF1A1)as unique to mCRC based on significant gene expression and survival outcomes.Moreover,its utility as a prognostic biomarker was confirmed using a pan-cancer analysis.Conclusions ALB-EEF1A1 may play a pivotal role in the metastatic transformation of primary CRC and significantly increase the risk of death.The identified ALB-EEF1A1 fusion transcripts are promising novel molecular targets that may serve as prognostic and diagnostic biomarkers and treatment targets for mCRC in the future.
基金The study is supported by Department of Biotechnology grant no.6242-P103/RGCB/PMD/DBT/SMSV/2015.Authors are thankful to the Ministry of Human Resource and Development,and CSIR Govt.of India,New Delhi,India for providing scholarship during this tenure.The authors acknowledge Dr.Tonima Kamat for critically reviewing the manuscript.
文摘Molecular subtypes-based therapies offer new potential framework for desired and precise outcome in clinical settings.Current treatment strategies in colorectal cancer are largely‘one drug fit all’model for patients that display same pathological conditions.However,CRC is a very heterogenous set ofmalignancy that does not support for above criteria.Each subtype displays different pathological and genetic signatures.Based on these features,therapeutic stratification for individual patients may be designed,which may ultimately lead to improved therapeutic outcomes.In this comprehensive review,we have attempted to briefly outline major CRC pathways.A detailed overview of molecular subtypes and their clinical significance has been discussed.Present and futuremethods,governing CRC subtyping in the era of personalized therapywith a special emphasis on CMS subtypes of CRC has been reviewed.Together,discovery and validation of new CRC patient stratification methods,screening for novel therapeutic targets,and enhanced diagnosis of CRC may improve the treatment outcome.
基金funded by the Department of Biotechnology India section order 6242-P103/RGCB/PMD/DBT/SMSV/2015.
文摘Colorectal cancer(CRC)is known to harbor considerable heterogeneity.1 Consequently,it could be hypothesized that similar-appearing tumors might exhibit substantial genetic differences while diverse-appearing tumors may have a similar genetic landscape.2 Due to these differences at the molecular level,they behave or respond differently to therapies as well.CRC progression is a multistep process and involves the accumulation of substantial genetic and epigenetic events in a stage-dependent manner.
