Systemic immune profiling analysis identifying M2-TAM related genes predicted colon cancer prognosis and chemotherapy responses DOI Creative Commons
Xiaopei Liu, Dan Liu,

Conge Tan

et al.

Medicine, Journal Year: 2024, Volume and Issue: 103(52), P. e40979 - e40979

Published: Dec. 27, 2024

Colon cancer (COAD) poses great challenges to clinical treatment due its heterogeneity and complex immune microenvironment. M2-like macrophages significantly influence COAD's onset, progression, treatment. Yet, existing macrophage markers are limited in prognostic efficacy, prompting the exploration of new M2 signatures. Extensive data analysis aimed unveil prognosis-associated M2-derived Bulk transcriptome, single-cell RNA sequencing, from The Cancer Genome Atlas Gene Expression Omnibus databases for patients with COAD were amassed. Cell-Type Identification by Estimating Relative Subsets Transcripts identified cell infiltration, Kaplan-Meier test crucial populations associated prognosis. Genetic signatures linked tumor-associated crafted utilizing weighted gene coexpression network analysis, least absolute shrinkage selection operator, Cox regression. signature was validated GSE17536. expression profile investigated sequencing dataset GSE166555. Systemic that has most significant significance Atlas-COAD. core genes related infiltration extracted analysis. Least operator-stepwise COX regression-derived (snail family zinc finger 1, gastrin-releasing peptide, gamma-aminobutyric acid type A receptor delta subunit, cluster differentiation 1B, poly(A)-binding protein cytoplasmic 2, manic fringe, death-associated kinase 1) as a risk model, which confirmed independent prognosis factors, external dataset. This M2-based model reflected infiltration. Mendelian randomization established cytotoxic T lymphocyte associate protein-4 274 checkpoints' causality COAD. In conclusion, our study developed novel discriminating predicting COAD, offering fresh perspectives interventions.

Language: Английский

Targeting C21orf58 is a Novel Treatment Strategy of Hepatocellular Carcinoma by Disrupting the Formation of JAK2/C21orf58/STAT3 Complex DOI Creative Commons
Hao Jiang, Yang Wang,

Doudou Wen

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(15)

Published: Feb. 11, 2024

Abstract Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. Functionally uncharacterized genes are an attractive repository to explore candidate oncogenes. It demonstrated that C21orf58 displays oncogenic role in promoting cell growth, tumorigenesis and sorafenib resistance HCC cells by abnormal activation STAT3 signaling. Mechanistically, a novel manner regulate signaling adaptor forms ternary complex reveal with N‐terminal domain SH2 JAK2, which overactivates wild‐type facilitating its phosphorylation mediated hyper‐activates constitutively mutated due preferred binding JAK2. Moreover, it validated inhibition drug alminoprofen, selected virtual screening, could effectively repress viability cells. Therefore, identified functions as adaptor, regulatory mechanism JAK2/STAT3 signaling, explain activity activated mutants STAT3, therapeutic potential targeting HCC.

Language: Английский

Citations

4
Non-coding RNAs Affect Breast Cancer Development Through the Notch Signaling Pathway: An Overview DOI Creative Commons
Alireza Ahmadi, Amin Moqadami, Mohammad Khalaj‐Kondori

et al.

Gene Expression, Journal Year: 2024, Volume and Issue: 23(1), P. 44 - 56

Published: Feb. 9, 2024

Breast cancer is the most prevalent malignancy and leading cause of cancer-related death in women. still an extremely difficult to treat due its significant metastasis. Mis-regulation Notch signaling components such as receptors/ligands their interaction breast sparks tumor initiation, maintenance, progression through induction abnormal tumorigenesis while modulating vascular integrity, drug resistance, invasion, migration. Numerous studies have shown that non-coding RNAs can regulate accordingly impact pathobiology. MiRNAs could directly or indirectly via sponging suppressing other genes involved pathway. Further, lncRNAs interact with miRNAs mRNAs, lncRNA-miRNA-mRNA networks function substantial mediators various pathways, including Also, by targeting genes, circRNAs induce tumorigenic properties Due intricacy human physiology, it challenging for standard drugs be effective, cells develop resistance treatment a self-renewal capacity. Moreover, because non-specific intervention targets both immune cells, may reverse effect regulating formation tumors. Thus, in-depth understanding mechanisms useful diagnosis, prognosis, development novel medications specifically target signaling, improving efficacy immunotherapy cancer. This review will discuss clarify which miRNAs, lncRNAs, affect pathway BC development.

Language: Английский

Citations

3
Comprehensive genomics analysis of aging related gene signature to predict the prognosis and drug resistance of colon adenocarcinoma DOI Creative Commons

Jubin Feng,

Fengyihuan Fu, Yuqiang Nie

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 28, 2023

Background: Colon adenocarcinoma (COAD) is a heterogeneous tumor and senescence crucial in the occurrence of cancer. This study aimed to identify senescence-based subtypes construct prognostic signature predict prognosis guide immunotherapy or chemotherapy decisions for COAD patients. Methods: Based on single-cell RNA sequencing (scRNA-seq) data 13 samples from Gene Expression Omnibus (GEO) database, we assessed cellular characteristics. Transcriptome data, copy number variations (CNVs) single nucleotide (SNVs) were obtained The Cancer Genome Atlas (TCGA) database. GSE39582 GSE17537 used validation. Senescence identified using unsupervised consensus clustering analysis, was developed univariate Cox analysis least absolute shrinkage selection operator (LASSO). Response risk groups predicted half-maximal inhibitory concentration (IC50) values. We further analyzed relationship between gene expression methylation level. prediction performance by nomogram. Results: Senescence-related pathways highly enriched malignant cells bulk RNA-seq verified senescence. Three identified, which patients clust3 had poorest higher T stage, accompanied with mutation burden (TMB) mutations, activated inflammatory response, more immune cell infiltration, escape tendency. A 11 genes (MFNG, GPRC5B, TNNT1, CCL22, NOXA1, PABPC1L, PCOLCE2, MID2, CPA3, HSPA1A, CALB1) established, accurately lower high Its robustness validated external cohort. Low sensitive small molecule drugs including Erlotinib, Sunitinib, MG-132, CGP-082996, AZ628, Sorafenib, VX-680, Z-LLNle-CHO. Risk score an independent factor nomogram confirmed its reliability. Four (CALB1, TNNT1) significant positive correlation their level, while six (CCL22, MFNG, PCOLCE2) negatively correlated Conclusion: provides novel understanding heterogeneity perspective senescence, develops signatures COAD.

Language: Английский

Citations

8
Systemic immune profiling analysis identifying M2-TAM related genes predicted colon cancer prognosis and chemotherapy responses DOI Creative Commons
Xiaopei Liu, Dan Liu,

Conge Tan

et al.

Medicine, Journal Year: 2024, Volume and Issue: 103(52), P. e40979 - e40979

Published: Dec. 27, 2024

Colon cancer (COAD) poses great challenges to clinical treatment due its heterogeneity and complex immune microenvironment. M2-like macrophages significantly influence COAD's onset, progression, treatment. Yet, existing macrophage markers are limited in prognostic efficacy, prompting the exploration of new M2 signatures. Extensive data analysis aimed unveil prognosis-associated M2-derived Bulk transcriptome, single-cell RNA sequencing, from The Cancer Genome Atlas Gene Expression Omnibus databases for patients with COAD were amassed. Cell-Type Identification by Estimating Relative Subsets Transcripts identified cell infiltration, Kaplan-Meier test crucial populations associated prognosis. Genetic signatures linked tumor-associated crafted utilizing weighted gene coexpression network analysis, least absolute shrinkage selection operator, Cox regression. signature was validated GSE17536. expression profile investigated sequencing dataset GSE166555. Systemic that has most significant significance Atlas-COAD. core genes related infiltration extracted analysis. Least operator-stepwise COX regression-derived (snail family zinc finger 1, gastrin-releasing peptide, gamma-aminobutyric acid type A receptor delta subunit, cluster differentiation 1B, poly(A)-binding protein cytoplasmic 2, manic fringe, death-associated kinase 1) as a risk model, which confirmed independent prognosis factors, external dataset. This M2-based model reflected infiltration. Mendelian randomization established cytotoxic T lymphocyte associate protein-4 274 checkpoints' causality COAD. In conclusion, our study developed novel discriminating predicting COAD, offering fresh perspectives interventions.

Language: Английский

Citations

0