Identification of tumor microenvironment‑associated immunological genes as potent prognostic markers in the cancer genome analysis project HOPE

Kidney cancer encompasses a range of primary cancers, such as clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Our knowledge about the tumor microenvironment (TME) of kidney cancer is still limited. Therefore, we comprehensively assessed the TME of kidney cancers (including ccRCC and pRCC) using the ESTIAMTE, and CIBERSORT algorithms, and conducted distinct functional and correlation analyses with data from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Connectivity map and CellMiner database. Next, we identified two immune-related hub genes, IGLL5 and IL2RA, which play essential roles in the TME as well as on survival in ccRCC and pRCC. Furthermore, ccRCC and pRCC samples from our medical center were collected to verify the clinical application value of these two immune-related genes. A specific enrichment analysis of immune cells related to IGLL5 and IL2RA was also conducted in two types of renal cell cancer. Based on selected genes, we predicted the drug response and uncovered novel drug candidate for RCC treatment. Considering the unfavorable outcomes of kidney cancer and emerging interest in TME-targeted treatments, our results may offer insights into immune-related molecular mechanisms and possible targets to control the kidney cancer.

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A framework for generating interactive reports for cancer genome analysis

The Journal of Open Source Software ◽

10.21105/joss.00457 ◽

2017 ◽

Vol 2 (20) ◽

pp. 457 ◽

Cited By ~ 1

Author(s):

Ai Okada ◽

Kenichi Chiba ◽

Hiroko Tanaka ◽

Satoru Miyano ◽

Yuichi Shiraishi

Keyword(s):

Genome Analysis ◽

Cancer Genome

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Decoding the Roles of Astrocytes and Hedgehog Signaling in Medulloblastoma

Current Oncology ◽

10.3390/curroncol28040267 ◽

2021 ◽

Vol 28 (4) ◽

pp. 3058-3070

Author(s):

Terence Teixeira Duarte ◽

Silvia Aparecida Teixeira ◽

Luis Gonzalez-Reyes ◽

Rui Manuel Reis

Keyword(s):

Tumor Microenvironment ◽

Sonic Hedgehog ◽

Stromal Cells ◽

Hedgehog Signaling ◽

Prognostic Markers ◽

Therapeutic Strategies ◽

Molecular Networks ◽

Transduction Mechanisms ◽

Tumoral Cells ◽

Multiple Interactions

The molecular evolution of medulloblastoma is more complex than previously imagined, as emerging evidence suggests that multiple interactions between the tumor cells and components of the tumor microenvironment (TME) are important for tumor promotion and progression. The identification of several molecular networks within the TME, which interact with tumoral cells, has provided new clues to understand the tumorigenic roles of many TME components as well as potential therapeutic targets. In this review, we discuss the most recent studies regarding the roles of astrocytes in supporting sonic hedgehog (SHH) subgroup medulloblastoma (MB) and provide an overview of MB progression through SHH expression and signal transduction mechanisms into the complex tumor microenvironment. In addition, we highlight the associations between tumor and stromal cells as possible prognostic markers that could be targeted with new therapeutic strategies.

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Tumor Extracellular Matrix Remodeling: New Perspectives as a Circulating Tool in the Diagnosis and Prognosis of Solid Tumors

Cells ◽

10.3390/cells8020081 ◽

2019 ◽

Vol 8 (2) ◽

pp. 81 ◽

Cited By ~ 15

Author(s):

Marta Giussani ◽

Tiziana Triulzi ◽

Gabriella Sozzi ◽

Elda Tagliabue

Keyword(s):

Extracellular Matrix ◽

Tumor Microenvironment ◽

Tumor Tissue ◽

Prognostic Markers ◽

Complex Mixture ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Ecm Remodeling ◽

Diagnosis And Prognosis ◽

Novel Concept

: In recent years, it has become increasingly evident that cancer cells and the local microenvironment are crucial in the development and progression of tumors. One of the major components of the tumor microenvironment is the extracellular matrix (ECM), which comprises a complex mixture of components, including proteins, glycoproteins, proteoglycans, and polysaccharides. In addition to providing structural and biochemical support to tumor tissue, the ECM undergoes remodeling that alters the biochemical and mechanical properties of the tumor microenvironment and contributes to tumor progression and resistance to therapy. A novel concept has emerged, in which tumor-driven ECM remodeling affects the release of ECM components into peripheral blood, the levels of which are potential diagnostic or prognostic markers for tumors. This review discusses the most recent evidence on ECM remodeling-derived signals that are detectable in the bloodstream, as new early diagnostic and risk prediction tools for the most frequent solid cancers.

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Cancer genome analysis: a landscape seen from many angles

Drug Discovery Today Disease Mechanisms ◽

10.1016/j.ddmec.2008.05.003 ◽

2007 ◽

Vol 4 (4) ◽

pp. 269-276

Author(s):

Henrik Edgren ◽

Maija Wolf ◽

Olli Kallioniemi ◽

Matthias Nees

Keyword(s):

Genome Analysis ◽

Cancer Genome

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Next‐generation sequencing in residual liquid‐based cytology specimens for cancer genome analysis

Diagnostic Cytopathology ◽

10.1002/dc.24511 ◽

2020 ◽

Vol 48 (11) ◽

pp. 965-971 ◽

Cited By ~ 1

Author(s):

Tomomi Yamaguchi ◽

Toshiaki Akahane ◽

Ohi Harada ◽

Yasutaka Kato ◽

Eriko Aimono ◽

...

Keyword(s):

Next Generation Sequencing ◽

Genome Analysis ◽

Cancer Genome ◽

Residual Liquid ◽

Next Generation ◽

Liquid Based Cytology ◽

Generation Sequencing

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CGARS: cancer genome analysis by rank sums

Bioinformatics ◽

10.1093/bioinformatics/btu011 ◽

2014 ◽

Vol 30 (9) ◽

pp. 1295-1296 ◽

Cited By ~ 4

Author(s):

Xin Lu ◽

Roman K. Thomas ◽

Martin Peifer

Keyword(s):

Genome Analysis ◽

Cancer Genome

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Exosomes: Small EVs with Large Immunomodulatory Effect in Glioblastoma

International Journal of Molecular Sciences ◽

10.3390/ijms22073600 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3600

Author(s):

Laura Benecke ◽

Mali Coray ◽

Sandra Umbricht ◽

Dapi Chiang ◽

Fabrício Figueiró ◽

...

Keyword(s):

Tumor Microenvironment ◽

Immune Cells ◽

Prognostic Markers ◽

Survival Rates ◽

Tumor Proliferation ◽

Structural And Functional Properties ◽

Immunosuppressive Tumor Microenvironment ◽

Aggressive Tumor ◽

Aggressive Tumors ◽

Resistance To Chemotherapy

Glioblastomas are among the most aggressive tumors, and with low survival rates. They are characterized by the ability to create a highly immunosuppressive tumor microenvironment. Exosomes, small extracellular vesicles (EVs), mediate intercellular communication in the tumor microenvironment by transporting various biomolecules (RNA, DNA, proteins, and lipids), therefore playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Exosomes are found in all body fluids and can cross the blood–brain barrier due to their nanoscale size. Recent studies have highlighted the multiple influences of tumor-derived exosomes on immune cells. Owing to their structural and functional properties, exosomes can be an important instrument for gaining a better molecular understanding of tumors. Furthermore, they qualify not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting aggressive tumor cells, like glioblastomas.

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Molecular Profiling of Core Immune-Escape Genes Highlights LCK Has Potential to Reshape TME in Melanoma

10.21203/rs.3.rs-923242/v1 ◽

2021 ◽

Author(s):

Duoli Zhang ◽

Zhuo Zhang ◽

Shixin Xiang ◽

Mintao Xiao ◽

Yao Zhang ◽

...

Keyword(s):

Prognostic Factors ◽

Immune System ◽

Tumor Microenvironment ◽

Immune Escape ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Cox Regression Analysis ◽

Tumor Environment ◽

Cancer Genome Atlas ◽

Genome Atlas

Abstract Background: The game between the immune system of the organism and the tumor is a dynamic course of events. Once the escape phase is reached, the tumor will overcome the limitations of the immune system and the tumor will progress. Objective: This study aimed to determine the potential tumor environment-based prognostic biomarkers related to immunotherapy in melanoma. Methods: 471 tumor samples and 398 normal samples were extracted from The Cancer Genome Atlas and The Genotype-Tissue Expression. Furthermore, a core set of immune-escape genes were collected from previous studies and a set of immune-related genes were obtained from IMMPORT database. Through overlapping these two sets of genes, a set of core immune-escape related genes were identified. In the next place, we conducted a systematic analysis of core immune-escape related genes through The Cancer Genome Atlas cohort and identified independent prognostic factors in melanoma. Through CIBERSORT, ssGSEA algorithm and TIMER database, we explored the potential of independent prognostic factors to reshape the tumor microenvironment.Results: Through Kaplan-Meier as well as univariate cox regression analysis of expression profiles and clinical information obtained from the TCGA cohort, we found that high LCK expression was associated with prolonged overall survival. In addition, the expression level of LCK was significantly correlated with the dysregulation of the infiltration level of immune cells in the tumor microenvironment. Conclusions: In this study, we determined LCK as a biomarker that is significantly associated with tumor environment and has significant prognostic significance. Meanwhile, immunotherapeutic approaches targeting LCK in tumor cells may provide a new perspective for the treatment of melanoma.

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