Bioinformatics Data Mining Repurposes the JAK2 (Janus Kinase 2) Inhibitor Fedratinib for Treating Pancreatic Ductal Adenocarcinoma by Reversing the KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog)-Driven Gene Signature

Liu, Li Wei; Hsieh, Yao Yu; Yang, Pei Ming

doi:10.3390/jpm10030130

Cited by 18 publications

(13 citation statements)

References 57 publications

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“…However, in nearly one-third of patients, cancerous growth has already spread to regional lymph nodes at the time of diagnosis [67]. Therefore, it is necessary to investigate novel prognostic techniques for early-stage detection, which employ new biomarkers in a vital role [68][69][70][71][72][73]. Furthermore, characterizing the immune system, profiling the TME, and constructing BRCA immunotherapies are also known as critical keys in cancer research [74,75].…”

Section: Discussionmentioning

confidence: 99%

Potential Therapeutic and Prognostic Values of LSM Family Genes in Breast Cancer

Wang

Phan

et al. 2021

Cancers

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In recent decades, breast cancer (BRCA) has become one of the most common diseases worldwide. Understanding crucial genes and their signaling pathways remain an enormous challenge in evaluating the prognosis and possible therapeutics. The “Like-Smith” (LSM) family is known as protein-coding genes, and its member play pivotal roles in the progression of several malignancies, although their roles in BRCA are less clear. To discover biological processes associated with LSM family genes in BRCA development, high-throughput techniques were applied to clarify expression levels of LSMs in The Cancer Genome Atlas (TCGA)-BRCA dataset, which was integrated with the cBioPortal database. Furthermore, we investigated prognostic values of LSM family genes in BCRA patients using the Kaplan–Meier database. Among genes of this family, LSM4 expression levels were highly associated with poor prognostic outcomes with a hazard ratio of 1.35 (95% confidence interval 1.21–1.51, p for trend = 3.4 × 10−7). MetaCore and GlueGo analyses were also conducted to examine transcript expression signatures of LSM family members and their coexpressed genes, together with their associated signaling pathways, such as “Cell cycle role of APC in cell cycle regulation” and “Immune response IL-15 signaling via MAPK and PI3K cascade” in BRCA. Results showed that LSM family members, specifically LSM4, were significantly correlated with oncogenesis in BRCA patients. In summary, our results suggested that LSM4 could be a prospective prognosticator of BRCA.

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Section: Discussionmentioning

confidence: 99%

Potential Therapeutic and Prognostic Values of LSM Family Genes in Breast Cancer

Wang

Phan

et al. 2021

Cancers

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“…Besides, a recent study from Liu et al. found that TG-101348 could exhibit KRAS-dependent anticancer activity in pancreatic ductal adenocarcinoma cell [101] . Vinorelbine is a common chemotherapy medication for the treatment of non-small cell lung cancer and other types of cancer [ 102 , 103 ].…”

Section: Discussionmentioning

confidence: 99%

“…Phase 2 clinical trial of TG-101348 on patients with ruxolitinibresistant or ruxolitinib-intolerant myelofibrosis showed that patients could obtain significant clinical benefit with TG-101348 [100]. Besides, a recent study from Liu et al found that TG-101348 could exhibit KRAS-dependent anticancer activity in pancreatic ductal adenocarcinoma cell [101]. Vinorelbine is a common chemotherapy medication for the treatment of non-small cell lung cancer and other types of cancer [102,103].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma

Chen

et al. 2021

EBioMedicine

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Background Esophageal squamous cell carcinoma (ESCC) remains one of the deadly cancer types. Comprehensively dissecting the molecular characterization and the heterogeneity of ESCC paves the way for developing more promising therapeutics. Methods Expression profiles of multiple ESCC datasets were integrated. ATAC-seq and RNA-seq were combined to reveal the chromatin accessibility features. A prognosis-related subtype classifier (PrSC) was constructed, and its association with the tumor microenvironment (TME) and immunotherapy was assessed. The key gene signature was validated in clinical samples. Based on the TME heterogeneity of ESCC patients, potential subtype-specific therapeutic agents were screened. Findings The common differentially expressed genes (cDEGs) in ESCC were identified. Up-regulated genes (HEATR1, TIMELESS, DTL, GINS1, RUVBL1, and ECT2) were found highly important in ESCC cell survival. The expression alterations of PRIM2, HPGD, NELL2, and TFAP2B were associated with chromatin accessibility changes. PrSC was a robust scoring tool that was not only associated with the prognosis of ESCC patients, but also could reflect the TME heterogeneity. TNS1 high fibroblasts were associated with immune exclusion. TG-101348 and Vinorelbine were identified as potential subtype-specific therapeutic agents. Besides, the application of PrSC into two immunotherapy cohorts indicated its potential value in assessing treatment response to immunotherapy. Interpretation Our study depicted the multi-dimensional characterization of ESCC, established a robust scoring tool for the prognosis assessment, highlighted the role of TNS1 high fibroblasts in TME, and identified potential drugs for clinical use. Funding A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

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“…Due to their expeditiousness and robustness in screening potential targets in diseases, high-throughput technologies are now playing critical roles in the biomedical fields. Various publicly available databases, including Gene Expression Omnibus (GEO), which covers more than 94,000 datasets and over 2 million samples, are widely employed in cancer research for both raw and processed dataset analyses [ 21 , 22 , 23 , 24 , 25 , 26 ]. Oncomine is mainly applied to numerous cancer types and subtypes to query mRNA gene expression profiles, and it offers multiple types of analysis, allowing researchers to compare variations in gene expressions between matched tumor and normal tissues [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of LAGEs Family Gene Signature and Prognostic Relevance in Breast Cancer

Tang

Phan

et al. 2021

Diagnostics

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Breast cancer (BRCA) is one of the most complex diseases and involves several biological processes. Members of the L-antigen (LAGE) family participate in the development of various cancers, but their expressions and prognostic values in breast cancer remain to be clarified. High-throughput methods for exploring disease progression mechanisms might play a pivotal role in the improvement of novel therapeutics. Therefore, gene expression profiles and clinical data of LAGE family members were acquired from the cBioportal database, followed by verification using the Oncomine and The Cancer Genome Atlas (TCGA) databases. In addition, the Kaplan-Meier method was applied to explore correlations between expressions of LAGE family members and prognoses of breast cancer patients. MetaCore, GlueGo, and GluePedia were used to comprehensively study the transcript expression signatures of LAGEs and their co-expressed genes together with LAGE-related signal transduction pathways in BRCA. The result indicated that higher LAGE3 messenger (m)RNA expressions were observed in BRCA tissues than in normal tissues, and they were also associated with the stage of BRCA patients. Kaplan-Meier plots showed that overexpression of LAGE1, LAGE2A, LAGE2B, and LAGE3 were highly correlated to poor survival in most types of breast cancer. Significant associations of LAGE family genes were correlated with the cell cycle, focal adhesion, and extracellular matrix (ECM) receptor interactions as indicated by functional enrichment analyses. Collectively, LAGE family members’ gene expression levels were related to adverse clinicopathological factors and prognoses of BRCA patients; therefore, LAGEs have the potential to serve as prognosticators of BRCA patients.

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Bioinformatics Data Mining Repurposes the JAK2 (Janus Kinase 2) Inhibitor Fedratinib for Treating Pancreatic Ductal Adenocarcinoma by Reversing the KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog)-Driven Gene Signature

Cited by 18 publications

References 57 publications

Potential Therapeutic and Prognostic Values of LSM Family Genes in Breast Cancer

Potential Therapeutic and Prognostic Values of LSM Family Genes in Breast Cancer

Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma

Analysis of LAGEs Family Gene Signature and Prognostic Relevance in Breast Cancer

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