Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer

Hoàng, Long; Domingo-Sabugo, C.; Starren, E.; Willis‐Owen, Saffron A.G.; Morris-Rosendahl, Deborah; Nicholson, Andrew G.; Cookson, William; Moffatt, Miriam F.

doi:10.1002/1878-0261.12568

Cited by 29 publications

(24 citation statements)

References 34 publications

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“…Eligible data sets in GEO were selected according to the following criteria and 11 data sets were obtained as of May 2020 (including 268 cases of control samples, 601 cases of lung tumor samples) (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Data sets details are listed in Table 1.…”

Section: Raw Datamentioning

confidence: 99%

GEO Data Mining Identifies OLR1 as a Potential Biomarker in NSCLC Immunotherapy

Liu

Wang

et al. 2021

Front. Oncol.

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Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The tumor immune microenvironment (TME) in NSCLC is closely correlated to tumor initiation, progression, and prognosis. TME failure impedes the generation of an effective antitumor immune response. In this study, we attempted to explore TME and identify a potential biomarker for NSCLC immunotherapy. 48 potential immune-related genes were identified from 11 eligible Gene Expression Omnibus (GEO) data sets. We applied the CIBERSORT computational approach to quantify bulk gene expression profiles and thereby infer the proportions of 22 subsets of tumor-infiltrating immune cells (TICs); 16 kinds of TICs showed differential distributions between the tumor and control tissue samples. Multiple linear regression analysis was used to determine the correlation between TICs and 48 potential immune-related genes. Nine differential immune-related genes showed statistical significance. We analyzed the influence of nine differential immune-related genes on NSCLC immunotherapy, and OLR1 exhibited the strongest correlation with four well-recognized biomarkers (PD-L1, CD8A, GZMB, and NOS2) of immunotherapy. Differential expression of OLR1 showed its considerable potential to divide TICs distribution, as determined by non-linear dimensionality reduction analysis. In immunotherapy prediction analysis with the comparatively reliable tool TIDE, patients with higher OLR1 expression were predicted to have better immunotherapy outcomes, and OLR1 expression was potentially highly correlated with PD-L1 expression, the average of CD8A and CD8B, IFNG, and Merck18 expression, T cell dysfunction and exclusion potential, and other significant immunotherapy predictors. These findings contribute to the current understanding of TME with immunotherapy. OLR1 also shows potential as a predictor or a regulator in NSCLC immunotherapy.

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Section: Raw Datamentioning

confidence: 99%

GEO Data Mining Identifies OLR1 as a Potential Biomarker in NSCLC Immunotherapy

Liu

Wang

et al. 2021

Front. Oncol.

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“…Human lung cancers are widely known highly heterogeneous as revealed by transcriptomic, genomic, epigenomic, and proteomic profiles analysis [ 7 , 25 , 26 ]. In this study, we provide the in vivo evidence showing that cancer cells at the invasive front exhibit a higher level of autophagic flux than cancer cells inside the tumor body do.…”

Section: Discussionmentioning

confidence: 99%

Autophagic flux in cancer cells at the invasive front in the tumor-stroma border

Yan

Zhang

Tan

et al. 2021

Aging

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Cancer cells at the invasive front directly interact with stromal tissue that provides a microenvironment with mechanical, nutrient, and oxygen supply characteristics distinct from those of intratumoral tissues. It has long been known that cancer cells at the invasive front and cancer cells inside the tumor body exhibit highly differentiated functions and behaviors. However, it is unknown whether cancer cells at different locations exhibit a variety of autophagic flux, an important catabolic process to maintain cellular homeostasis in response to environmental changes. Here, using transmission electron microscopy (TEM), we found that invading cancer cells at the invasive front, which show mesenchymal transcriptomic traits, exhibit higher autophagic flux than cancer cells inside the tumor body in human primary non-small cell lung cancer (NSCLC) tissues. This autophagic feature was further confirmed by a live cell autophagic flux monitoring system combined with a 3D organotypic invasion coculture system. Additionally, the increased autophagic flux endows cancer cells with invasive behavior and positively correlates with the advanced tumor stages and the reduced survival period of lung cancer patients. These findings expand the understanding of autophagic dynamics during cancer invasion.

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“…Novel drugs that target VEGF, including anti-VEGF antibodies, anti-VEGF receptor antibodies, and small-molecule tyrosine kinase inhibitors, are already available and approved for the treatment of various tumors, including lung cancer. 40 Besides, a large number of downregulated differentially expressed circRNAs have been associated with other tumor signaling pathways, such as platelet activation, 41 MAPK signaling, 42 and RAS signaling. 43 KEGG analysis showed that upregulated and differentially expressed circRNAs were mainly associated with RNA transport and ribosome biogenesis with potential targets for cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

<p>Profiling and Integrated Analysis of Differentially Expressed Circular RNAs in Plasma Exosomes as Novel Biomarkers for Advanced-Stage Lung Adenocarcinoma</p>

Lin¹,

Xiong²,

Liu³

et al. 2020

OTT

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Purpose Exosomes contain abundant circRNAs and are determined to be involved in the pathogenesis of lung adenocarcinoma (LUAD). Thus, our study aimed to explore new circRNAs in plasma exosomes that could be involved in such pathogenesis. Patients and Methods High-throughput sequencing was used in identifying the alterations in exosomal circRNA expression. Gene ontology functional analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to determine the significant functions and pathways associated with differentially expressed circRNAs. TargetScan and miRanda were used to predict circRNA-targeted microRNAs and mRNAs. CircRNA expression profiles were then validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Wound healing and Transwell assays were performed to determine the roles of has_circ_0102537 in LUAD progression. Results We identified six significantly upregulated and 214 significantly downregulated circRNAs. GO and KEGG pathway analysis suggested that the differentially expressed circRNAs are involved in the occurrence and development of LUAD. A circRNA–miRNA–mRNA meshwork was established to predict the potential interactions among these RNAs. The circRNA expression profile was then subjected to qRT-PCR for validation. We identified hsa_circ_0102537 to be downregulated in both LUAD plasma exosomes and tissues. GO, KEGG pathway analysis, circRNA–miRNA–mRNA meshwork, and further experiments suggest that hsa_circ_0102537 could be involved in LUAD progression. Conclusion Our study explored a large number of circRNAs that may be involved in the LUAD pathogenesis, thereby supporting the need for further research on both diagnosis biomarkers and the potential intervention therapeutic targets.

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Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer

Cited by 29 publications

References 34 publications

GEO Data Mining Identifies OLR1 as a Potential Biomarker in NSCLC Immunotherapy

GEO Data Mining Identifies OLR1 as a Potential Biomarker in NSCLC Immunotherapy

Autophagic flux in cancer cells at the invasive front in the tumor-stroma border

<p>Profiling and Integrated Analysis of Differentially Expressed Circular RNAs in Plasma Exosomes as Novel Biomarkers for Advanced-Stage Lung Adenocarcinoma</p>

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