In the postscreening era, physicians are in need of methods to discriminate aggressive from nonaggressive prostate cancer （PCa） to reduce overdiagnosis and overtreatment. However, studies have shown that prognoses ...In the postscreening era, physicians are in need of methods to discriminate aggressive from nonaggressive prostate cancer （PCa） to reduce overdiagnosis and overtreatment. However, studies have shown that prognoses （e.g., progression and mortality） differ even among individuals with similar clinical and pathological characteristics. Existing risk classifiers （TMN grading system, Gleason score, etc.） are not accurately enough to represent the biological features of PCa. Using new genomic technologies, novel biomarkers and classifiers have been developed and shown to add value to clinical or pathological risk factors for predicting aggressive disease. Among them, RNA testing （gene expression analysis） is useful because it can not only reflect genetic variations but also reflect epigenetic regulations. Commercially available RNA profiling tests （Oncotype Dx, Prolaris, and Decipher） have demonstrated strong abilities to discriminate PCa with poor prognosis from less aggressive diseases. For instance, these RNA profiling tests can predict disease progression in active surveillance patients or early recurrence after radical treatments. These tests may offer more dependable methods for PCa prognosis prediction to make more accurate and personal medical decisions.展开更多
DNA profiling is an established method for cancer treatment selection,while RNA profiling remains investigational.We explored associations between DNA and RNA alterations and between the number of genes with altered e...DNA profiling is an established method for cancer treatment selection,while RNA profiling remains investigational.We explored associations between DNA and RNA alterations and between the number of genes with altered expression and overall survival(OS)using patient data from IMPACT2(NCT02152254),a randomized study evaluating molecular profiling for guiding cancer therapy across tumor types.Molecular profiling,including DNA next-generation sequencing,was performed on all 829 patients in the IMPACT2 study.RNA profiling was performed by Tempus for 253 of 829 patients.We evaluated the concordance between DNA and RNA profiling,analyzed OS in 217 treated patients with RNA profiling,and assessed PD-L1 status and number of genes with altered expression.Fifty patients exhibited 58 concordant events,i.e.,genomic and expression alteration(s)in the same gene,including 38 copy number events,and 41 patients had statistically significant concordance.We identified 123 gene pairs with significant associations between genomic and expression alterations(p<0.05),including TP53 alterations with VEGFA overexpression.The median OS for patients with 0-2,3-5,and≥6 genes with altered expression was 9.8,11.9,and 6.7 months,respectively(p=0.03).These results underscore RNA profiling’s potential actionability,and altered expression in≥6 genes was associated with shorter OS.Significant concordance of TP53 alterations with VEGFA overexpression may partially explain tumor response to bevacizumab in TP53-mutant patients.展开更多
Body fluid identification through messenger RNA(mRNA)has been proposed as a useful supplement to presumptive and confirmatory tests by previous laboratory studies;however,its application in routine clinical forensic e...Body fluid identification through messenger RNA(mRNA)has been proposed as a useful supplement to presumptive and confirmatory tests by previous laboratory studies;however,its application in routine clinical forensic examination was rare.We report a case of sexual assault in which body fluid identification by mRNA profiling was used.Vaginal secretions mRNA markers(MUC4,HBD1,and CYP2B7P1)were used to test the sample,being obtained positive results.This case demonstrates that mRNA profiling of body fluids could be applied to routine case examinations as an aid,acting as a scientific collaborative evidence to strengthen the medicolegal opinion.展开更多
Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological bi...Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.展开更多
Background： Structure profiling experiments provide single-nucleotide information on RNA structure. Recent advances in chemistry combined with application of high-throughput sequencing have enabled structure profilin...Background： Structure profiling experiments provide single-nucleotide information on RNA structure. Recent advances in chemistry combined with application of high-throughput sequencing have enabled structure profiling at transeriptome scale and in living cells, creating unprecedented opportunities for RNA biology. Propelled by these experimental advances, massive data with ever-increasing diversity and complexity have been generated, which give rise to new challenges in interpreting and analyzing these data. Results： We review current practices in analysis of structure profiling data with emphasis on comparative and integrative analysis as well as highlight emerging questions. Comparative analysis has revealed structural patterns across transcriptomes and has become an integral component of recent profiling studies. Additionally, profiling data can be integrated into traditional structure prediction algorithms to improve prediction accuracy. Conclusions： To keep pace with experimental developments, methods to facilitate, enhance and refine such analyses are needed. Parallel advances in analysis methodology will complement profiling technologies and help them reach their full potential.展开更多
Epidermal growth factor receptor/mitogen-activated protein kinase(EGFR/MAPK)signaling is highly activated in various types of cancer.The long noncoding RNAs induced by this pathway and their roles in colorectal cancer...Epidermal growth factor receptor/mitogen-activated protein kinase(EGFR/MAPK)signaling is highly activated in various types of cancer.The long noncoding RNAs induced by this pathway and their roles in colorectal cancer(CRC)have not been fully elucidated.In this study,based on the profiling of long noncoding RNAs triggered by EGFR/MAPK signaling,we identified that ESSENCE(EGF[epidermal growth factor]Signal Sensing CAD’s Effect;ENST00000415336),which is mediated by the transcription factor early growth response factor 1,functions as a potent oncogenic molecule that predicts poor prognosis in CRC.Mechanistically,ESSENCE directly interacts with carbamoyl-phosphate synthetase 2,aspartate transcarbamylase,and dihydroorotase(CAD)and competitively attenuates CAD degradation mediated by its newly discovered E3 ligase KEAP1,thereby suppressing ferroptosis and promoting CRC progression.Importantly,combinational treatment of the mitogen-activated extracellular signal-regulated kinase inhibitor selumetinib and ferroptosis inducer sulfasalazine synergistically suppresses ESSENCE-high CRC in a patient-derived xenograft mouse model.Taken together,these findings demonstrate the crucial role of ESSENCE in mediating CRC progression by regulating CAD stabilization and suggest a therapeutic strategy of targeting the ESSENCE-CAD axis in CRC.展开更多
基金The work was supported by the National Natural Science Foundation of China （Grant No. 81402339）.
文摘In the postscreening era, physicians are in need of methods to discriminate aggressive from nonaggressive prostate cancer （PCa） to reduce overdiagnosis and overtreatment. However, studies have shown that prognoses （e.g., progression and mortality） differ even among individuals with similar clinical and pathological characteristics. Existing risk classifiers （TMN grading system, Gleason score, etc.） are not accurately enough to represent the biological features of PCa. Using new genomic technologies, novel biomarkers and classifiers have been developed and shown to add value to clinical or pathological risk factors for predicting aggressive disease. Among them, RNA testing （gene expression analysis） is useful because it can not only reflect genetic variations but also reflect epigenetic regulations. Commercially available RNA profiling tests （Oncotype Dx, Prolaris, and Decipher） have demonstrated strong abilities to discriminate PCa with poor prognosis from less aggressive diseases. For instance, these RNA profiling tests can predict disease progression in active surveillance patients or early recurrence after radical treatments. These tests may offer more dependable methods for PCa prognosis prediction to make more accurate and personal medical decisions.
基金supported in part by Mr.and Mrs.Steven McKenzie’s EndowmentKatherine Russell Dixie’s Distinguished Professorship Endowment+1 种基金donor funds from Jamie’s Hope and Mrs.and Mr.James Ritter for Dr.Tsimberidou’s Personalized Medicine Programin part also supported by the National Institutes of Health/National Cancer Institute award number P30 CA016672(University of Texas MD Anderson Cancer Center).
文摘DNA profiling is an established method for cancer treatment selection,while RNA profiling remains investigational.We explored associations between DNA and RNA alterations and between the number of genes with altered expression and overall survival(OS)using patient data from IMPACT2(NCT02152254),a randomized study evaluating molecular profiling for guiding cancer therapy across tumor types.Molecular profiling,including DNA next-generation sequencing,was performed on all 829 patients in the IMPACT2 study.RNA profiling was performed by Tempus for 253 of 829 patients.We evaluated the concordance between DNA and RNA profiling,analyzed OS in 217 treated patients with RNA profiling,and assessed PD-L1 status and number of genes with altered expression.Fifty patients exhibited 58 concordant events,i.e.,genomic and expression alteration(s)in the same gene,including 38 copy number events,and 41 patients had statistically significant concordance.We identified 123 gene pairs with significant associations between genomic and expression alterations(p<0.05),including TP53 alterations with VEGFA overexpression.The median OS for patients with 0-2,3-5,and≥6 genes with altered expression was 9.8,11.9,and 6.7 months,respectively(p=0.03).These results underscore RNA profiling’s potential actionability,and altered expression in≥6 genes was associated with shorter OS.Significant concordance of TP53 alterations with VEGFA overexpression may partially explain tumor response to bevacizumab in TP53-mutant patients.
文摘Body fluid identification through messenger RNA(mRNA)has been proposed as a useful supplement to presumptive and confirmatory tests by previous laboratory studies;however,its application in routine clinical forensic examination was rare.We report a case of sexual assault in which body fluid identification by mRNA profiling was used.Vaginal secretions mRNA markers(MUC4,HBD1,and CYP2B7P1)were used to test the sample,being obtained positive results.This case demonstrates that mRNA profiling of body fluids could be applied to routine case examinations as an aid,acting as a scientific collaborative evidence to strengthen the medicolegal opinion.
基金supported by Hunan Provincial Key Research and Development Program,No.2021SK2002(to BW)the Natural Science Foundation of Hunan Province of China(General Program),No.2021JJ30938(to YL)。
文摘Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.
文摘Background： Structure profiling experiments provide single-nucleotide information on RNA structure. Recent advances in chemistry combined with application of high-throughput sequencing have enabled structure profiling at transeriptome scale and in living cells, creating unprecedented opportunities for RNA biology. Propelled by these experimental advances, massive data with ever-increasing diversity and complexity have been generated, which give rise to new challenges in interpreting and analyzing these data. Results： We review current practices in analysis of structure profiling data with emphasis on comparative and integrative analysis as well as highlight emerging questions. Comparative analysis has revealed structural patterns across transcriptomes and has become an integral component of recent profiling studies. Additionally, profiling data can be integrated into traditional structure prediction algorithms to improve prediction accuracy. Conclusions： To keep pace with experimental developments, methods to facilitate, enhance and refine such analyses are needed. Parallel advances in analysis methodology will complement profiling technologies and help them reach their full potential.
基金supported by the National Key Research and Development Program of China(2020YFA0803300)the National Natural Science Foundation of China(82273133,82373139,82102973,and 82303028)+3 种基金the Open Fund of Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases(2020B1212060023)the Guangdong Basic and Applied Basic Research Foundation(2023A1515030261 and 2021A1515012081)the Guangzhou Science and Technology Program Project(2025A03J4388,202206010167,and 202201011425)the National Key Clinical Discipline,the program of Guangdong Provincial Clinical Research Center for Digestive Diseases(2020B1111170004).
文摘Epidermal growth factor receptor/mitogen-activated protein kinase(EGFR/MAPK)signaling is highly activated in various types of cancer.The long noncoding RNAs induced by this pathway and their roles in colorectal cancer(CRC)have not been fully elucidated.In this study,based on the profiling of long noncoding RNAs triggered by EGFR/MAPK signaling,we identified that ESSENCE(EGF[epidermal growth factor]Signal Sensing CAD’s Effect;ENST00000415336),which is mediated by the transcription factor early growth response factor 1,functions as a potent oncogenic molecule that predicts poor prognosis in CRC.Mechanistically,ESSENCE directly interacts with carbamoyl-phosphate synthetase 2,aspartate transcarbamylase,and dihydroorotase(CAD)and competitively attenuates CAD degradation mediated by its newly discovered E3 ligase KEAP1,thereby suppressing ferroptosis and promoting CRC progression.Importantly,combinational treatment of the mitogen-activated extracellular signal-regulated kinase inhibitor selumetinib and ferroptosis inducer sulfasalazine synergistically suppresses ESSENCE-high CRC in a patient-derived xenograft mouse model.Taken together,these findings demonstrate the crucial role of ESSENCE in mediating CRC progression by regulating CAD stabilization and suggest a therapeutic strategy of targeting the ESSENCE-CAD axis in CRC.
