Genetic Variants of ANGPT1, CD39, FGF2 and MMP9 Linked to Clinical Outcome of Bevacizumab Plus Chemotherapy for Metastatic Colorectal Cancer

Gaibar, María; Galán, Miguel; Romero‐Lorca, Alicia; Antón, Beatriz Flores; Malón, Diego; Moreno, Amàlia; Fernández-Santander, Ana; Novillo, Apolonia

doi:10.3390/ijms22031381

Cited by 6 publications

(5 citation statements)

References 52 publications

(74 reference statements)

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“…Several studies have shown that CXCL13 is involved to mediate 5-Fu resistance mechanism and considered to be a biomarker for predicting the prognosis of colorectal cancer, which is consistent with our ndings (47,48). FGF2, a member of the broblast growth factor (FGF) family whose signaling network has been implicated in several pathways, such as normal cell growth, differentiation, angiogenesis and tumor development, signi cantly promotes tumor cell differentiation and proliferation (49,50). FGF7, also called keratinocyte growth factor (KGF), is involved in inducing vascular endothelial growth factor (VEGF)-A expression, which plays important roles in the angiogenesis and metastasis of various cancer cells including colorectal cancer (51,52).…”

Section: Discussionmentioning

confidence: 99%

Development and validation of immune-related genomics nomogram for prognostic prediction in left- and right-side colorectal cancer

Niu

Chen

et al. 2022

Preprint

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Background: Previous studies have reported that the tumor heterogeneity and immune molecular mechanisms of proximal and distal colorectal cancer (CRC) are divergent. Therefore, our study aims to analyze the difference between left-sided CRC (LCC) and right-sided CRC (RCC), and respectively develop the nomograms based on prognostic immune-related genes for LCC and RCC. Methods: We enrolled 443 colon cancer patients (220 LCC patients and 223 patients) from The Cancer Genome Atlas (TCGA) datasets. Firstly, the differential expressed immune-related genes (DE-IRGs), overall survival (OS), and biological functions between LCC and RCC groups were identified. Then, we analyzed the differences between the two groups in the immune microenvironment, immune checkpoint, and tumor mutation burden (TMB). Next, the LCC and RCC data from TCGA dataset are randomly divided into training and internal validation sets at a 7:3 ratio respectively. Additionally, 566 colon cancer patients (342 LCC patients and 224 RCC patients) in the GSE39582 dataset were downloaded from the Gene Expression Omnibus (GEO) database as the external validation set. Then, survival and Lasso Cox regression analyses were applied to identify hub immune-related genes and respectively establish two prognostic gene signatures of LCC and RCC groups. The prognostic signatures were validated by the 10-fold cross-validation, internal validation set, and external validation set. Further, combined with clinical features, we constructed two clinical predictive nomograms and validated them. Results: RCC patients have lower survival than LCC. RCC patients have higher proportions of T cells CD8, T cells follicular helper, and lower macrophages M0, T cells CD4 naive. RCC patients have higher ESTIMATE and immune scores and lower tumor purity. The immune checkpoint expression levels and TMB values are higher in RCC patients than in LCC. We respectively selected 10 immune-related genes for LCC and 7 genes for RCC groups to develop and validate the prognostic model and calculate a risk score for each patient. The AUC values of the risk score for OS in LCC were 0.735 in the training set, 0.711 in the internal validation set, and 0.744 in the external validation set, and in RCC were 0.704 in the training set, 0.738 in the internal validation set, and 0.705 in the external validation set. The AUC values of the 10-fold cross-validation range from 0.564 to 0.808 in LCC and from 0.589 to 0.792 in RCC. The nomogram of LCC of RCC includes risk based on prognostic genes, age, pathological T, N, M, stage, and gender. the AUC values of the LCC nomogram were 0.722 in the training set, 0.696 in the internal validation set, and 0.739 in the external validation set, and of the RCC nomogram were 0.774 in the training set, 0.744 in the internal validation set, and 0.737 in the external validation set. We also found that were significantly different between high- and low-risk patients in the immune score, ESTIMATE score, tumor purity, immune checkpoint expression levels, and TMB values. Conclusions: We found significant differences in the multidimensional insight between LCC and RCC patients in clinical features, DE-IRGs, TMB, immune checkpoint expression levels, and immune microenvironment landscape. Our study respectively established two prognostic nomograms based on DE-IRGs in combination with clinical features to provide a basis for personalized and precise treatment of LCC and RCC patients.

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Section: Discussionmentioning

confidence: 99%

Development and validation of immune-related genomics nomogram for prognostic prediction in left- and right-side colorectal cancer

Niu

Chen

et al. 2022

Preprint

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“…Many kinds of drugs are used to treat tumours. For example, bevacizumab is used to treat advanced ovarian cancer, 39 metastatic colorectal cancer 40 and non-small cell lung cancer. 41 Bicalutamide is used to treat metastatic hormone-sensitive prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of Choriocarcinoma-Related MicroRNA-Transcription Factor-Target Gene Regulatory Networks and Validation of Key miRNAs

Peng¹,

Zhang²,

Mo³

et al. 2021

OTT

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Objective The aim of the current research was to construct a miRNA-transcription factor (TF)-target gene regulatory network in order to investigate the mechanism underlying choriocarcinoma and to verify the network through the overexpression or silencing of hub miRNAs in vitro. Materials and Methods A mRNA expression dataset and two miRNA expression datasets were analysed to identify differentially expressed genes (DEGs) and miRNAs (DEMs) between normal cells and choriocarcinoma cells. The top 400 upregulated and downregulated DEGs were identified as candidate DEGs, which were then mapped to construct protein–protein interaction (PPI) networks and select hub genes. Moreover, the DGIdb database was utilized to select candidate drugs for hub genes. Moreover, DEM target genes were predicted through the miRWalk2.0 database and overlaid with candidate DEGs to identify the differentially expressed target genes (DETGs). Furthermore, we established miRNA-TF-target gene regulatory networks and performed functional enrichment analysis of hub DEMs. Finally, we transfected mimics or inhibitors of hub DEMs into choriocarcinoma cells and assessed cell proliferation and migration to verify the vital role of hub DEMs in choriocarcinoma. Results A total of 140 DEMs and 400 candidate DEGs were screened from choriocarcinoma cells and normal cells. A PPI network of 400 candidate DEGs was established. Twenty-nine hub genes and 99 associated small molecules were identified to provide potential target drugs for choriocarcinoma treatment. We obtained 70 DETGs of DEMs derived from the intersection between predicted miRNA target genes and candidate DEGs. Subsequently, 3 hub DEMs were selected, and miRNA-TF-target gene regulatory networks containing 4 TFs, 3 TFs and 3 TFs for each network were constructed. The RT-PCR results confirmed that miR-29b-3p was highly expressed and that miR-519c-3p and miR-520a-5p were expressed at low levels in choriocarcinoma cells. The overexpression or silencing results suggested that 3 dysregulated hub DEMs jointly accelerated the proliferation and migration of choriocarcinoma. Conclusion Association of miRNA-TF-target gene regulatory networks may help us explore the underlying mechanism and provide potential targets for the diagnosis and treatment of choriocarcinoma.

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“…27 Fortunately, we found that Maria Gaibar and colleagues explored in 2021 that polymorphisms of angiogenesis pathway genes (ANGPT1, CD39, FGF2, and MMP9) were associated with clinical outcome of bevacizumab plus chemotherapy for metastatic colorectal cancer. 19 EJ Lewintre and colleagues reported recently that polymorphism of VEGFR-1 and VEGF-A and plasma levels of VEGF-A predicted the efficacy and prognosis of patients with nonsquamous NSCLC receiving chemotherapy combined with bevacizumab administration. 28 Collectively, polymorphism in the gene at the pathway single of bevacizumab disposition was proved to be of certain clinical significance for bevacizumab-based regimen.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, this study was designed as a real-world retrospective study just as the previous polymorphism study regarding bevacizumab-based therapy did. 19…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, this study was designed as a real-world retrospective study just as the previous polymorphism study regarding bevacizumab-based therapy did. 19 Patients with advanced or recurrent NSCLC who were administered with bevacizumab-based regimens as first-line therapy from January 2016 to October 2020 in the department of thoracic surgery of Shanxi Cancer Hospital were participated in this study. This study was undertaken in accordance with good clinical practice guidelines and the protocol was approved by the ethics committees of Shanxi Cancer Hospital (approved number: KY2020136).…”

Section: Study Design and Patient Enrollmentmentioning

confidence: 99%

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Influence of GSTP1 Polymorphism on the Clinical Outcomes of Patients With Advanced NSCLC Receiving First-Line Bevacizumab-Based Regimen: A Real-World Retrospective Study

Han

Tian

Jin

et al. 2021

Clin Med Insights Oncol

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Background: This study was to investigate the influence of GSTP1 gene polymorphism on the clinical outcomes of patients with advanced non-small-cell lung cancer (NSCLC) receiving first-line bevacizumab plus chemotherapy regimen. Methods: A total of 128 patients with advanced NSCLC who were administered with bevacizumab-based first-line regimens were recruited in this study. Available blood specimen and peripheral blood mononuclear cells (PBMCs) of the patients were obtained for the analysis of polymorphism and GSTP1 gene mRNA expression, respectively. The association between genotype status and clinical outcomes and other variates was analyzed and presented. Results: The prevalence of rs1695 were in accordance with Hardy-Weinberg Equilibrium ( P = .978). Patients with GG and AG genotypes were merged in a pattern of dominant inheritance to seek for the potentially clinical significance. Analysis of efficacy exhibited that the objective response rate (ORR) of patients with AA genotype and AG/GG genotypes were 62.1% (54/87) and 51.2% (21/41) ( P = 0.245). Prognosis demonstrated that the median progression-free survival (PFS) of patients with AA genotype and AG/GG genotypes were 9.5 and 5.6 months, respectively ( P = .007). Furthermore, the median overall survival (OS) of the two genotypes were 22.0 and 16.6 months, respectively ( P = .003). In addition, adjusted in multivariate Cox analysis for OS, AG/GG genotype was an independent factor for OS. Interestingly, mRNA analysis suggested that the mRNA expression of GSTP1 in PBMC of the patients with AG/GG genotypes of rs1695 polymorphism was significantly higher than those of patients with AA genotype ( P < .001). Conclusion: GSTP1 polymorphism rs1695 could be used for the prognostic evaluation of patients with advanced NSCLC receiving bevacizumab combined chemotherapy regimen.

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Genetic Variants of ANGPT1, CD39, FGF2 and MMP9 Linked to Clinical Outcome of Bevacizumab Plus Chemotherapy for Metastatic Colorectal Cancer

Cited by 6 publications

References 52 publications

Development and validation of immune-related genomics nomogram for prognostic prediction in left- and right-side colorectal cancer

Development and validation of immune-related genomics nomogram for prognostic prediction in left- and right-side colorectal cancer

Bioinformatics Analysis of Choriocarcinoma-Related MicroRNA-Transcription Factor-Target Gene Regulatory Networks and Validation of Key miRNAs

Influence of GSTP1 Polymorphism on the Clinical Outcomes of Patients With Advanced NSCLC Receiving First-Line Bevacizumab-Based Regimen: A Real-World Retrospective Study

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