Genetic and Immunohistochemical Expression of Integrins ITGAV, ITGA6, and ITGA3 As Prognostic Factor for Colorectal Cancer: Models for Global and Disease-Free Survival

Linhares, Marcelo Moura; Affonso, Regina; Viana, Luciano de Souza; Silva, Sandra Regina Morini; Denadai, Marcos Vinicius Araújo; Toledo, Sílvia Regina Caminada de; Matos, Délcio

doi:10.1371/journal.pone.0144333

Cited by 31 publications

(21 citation statements)

References 30 publications

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“…Consistent with our results, ITGA6 overexpression was observed in esophageal cancer [48] and colon cancer, [49] and it not only mediates interaction with the ECM but also drives intracellular signaling events that communicate from the tumor microenvironment to inside of the tumor cell to alter phenotypes including migration and invasion. [50] The associations of the ITGA6 with prognosis in cancer is poorly known, with limited studies reporting that this gene affects the prognosis of prostate cancer by influencing the biological characteristics of CSC, [51] and its high expression exhibited significantly poorer OS, [52] which is consistent with our finding in ovarian cancer (Fig. 5).…”

Section: Discussionsupporting

confidence: 89%

STROBE-compliant integrin through focal adhesion involve in cancer stem cell and multidrug resistance of ovarian cancer

et al. 2017

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Cancer stem cells (CSCs) are considered to be the root of carcinoma relapse and drug resistance in ovarian cancer. Hunting for the potential CSC genes and explain their functions would be a feasible strategy to meet the challenge of the drug resistance in ovarian cancer. In this study, we performed bioinformatic approaches such as biochip data extraction and pathway enrichment analyses to elucidate the mechanism of the CSC genes in regulation of drug resistance. Potential key genes, integrins, were identified to be related to CSC in addition to their associations with drug resistance and prognosis in ovarian cancer. A total of 36 ovarian CSC genes involved in regulation of drug resistance were summarized, and potential drug resistance-related CSC genes were identified based on 3 independent microarrays retrieved from the Gene Expression Omnibus (GEO) Profiles. Pathway enrichment of CSC genes associated with drug resistance in ovarian cancer indicated that focal adhesion signaling might play important roles in CSC genes-mediated drug resistance. Integrins are members of the adhesion molecules family, and integrin subunit alpha 1, integrin subunit alpha 5, and integrin subunit alpha 6 (ITGA6) were identified as central CSC genes and their expression in side population cells, cisplatin-resistant SKOV3 (SKOV3/DDP2) cells, and cisplatin-resistant A2780 (A2780/DDP) cells were dysregulated as measured by real-time quantitative polymerase chain reaction. The high expression of ITGA6 in 287 ovarian cancer patients of TCGA cohort was significantly associated with poorer progression-free survival. This study provide the basis for further understanding of CSC genes in regulation of drug resistance in ovarian cancer, and integrins could be a potential biomarker for prognosis of ovarian cancer.

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Section: Discussionsupporting

confidence: 89%

STROBE-compliant integrin through focal adhesion involve in cancer stem cell and multidrug resistance of ovarian cancer

et al. 2017

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“…For instance, among the "early stage," specific open chromatin genes were ITGAV and ITGA6, which interacted with vitronectin and laminin, respectively. These two genes were reported to be prognostic indicators in multiple cancers, including NSCLC, whose high expression correlated to longer survival time (32). On the other hand, we identified 6,664 chromatin regions that were specifically closed in the "early stage" cluster.…”

Section: Generation Of Matched Atac-seq Genome and Transcriptome Damentioning

confidence: 79%

The Open Chromatin Landscape of Non–Small Cell Lung Carcinoma

Wang

Xia

et al. 2019

Cancer Research

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Non-small cell lung carcinoma (NSCLC) is a major cancer type whose epigenetic alteration remains unclear. We analyzed open chromatin data with matched whole-genome sequencing and RNA-seq data of 50 primary NSCLC cases. We observed high interpatient heterogeneity of open chromatin profiles and the degree of heterogeneity correlated to several clinical parameters. Lung adenocarcinoma and lung squamous cell carcinoma (LUSC) exhibited distinct open chromatin patterns. Beyond this, we uncovered that the broadest open chromatin peaks indicated key NSCLC genes and led to less stable expression. Furthermore, we found that the open chromatin peaks were gained or lost together with somatic copy number alterations and affected the expression of important NSCLC genes. In addition, we identified 21 joint-quantitative trait loci (joint-QTL) that correlated to both assay for transposase accessible chromatin sequencing peak intensity and gene expression levels. Finally, we identified 87 regulatory risk loci associated with lung cancer-related phenotypes by intersecting the QTLs with genome-wide association study significant loci. In summary, this compendium of multiomics data provides valuable insights and a resource to understand the landscape of open chromatin features and regulatory networks in NSCLC.Significance: This study utilizes state of the art genomic methods to differentiate lung cancer subtypes.

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“…Cells were then fixed, permeabilised and incubated with HRP-conjugated rabbit antimouse (1:1000, STAR13B, AbD Serotec) and the absorbance of each sample measured at 450 nm. (2020) 10:537 | https://doi.org/10.1038/s41598-019-57287-w www.nature.com/scientificreports www.nature.com/scientificreports/ and lower DFS in patients with colorectal tumours 34 and shorter survival in pancreatic cancer 35 . High levels of ITGA3 correlate with more aggressive phenotypes and poor prognosis in patients with colorectal cancer and pancreatic ductal adenocarcinoma 36,27 .…”

Section: Discussionmentioning

confidence: 99%

Development and application of two novel monoclonal antibodies against overexpressed CD26 and integrin α3 in human pancreatic cancer

Arias-Pinilla

Dalgleish

Mudan

et al. 2020

Sci Rep

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Monoclonal antibody (mAb) technology is an excellent tool for the discovery of overexpressed cell surface tumour antigens and the development of targeting agents. Here, we report the development of two novel mAbs against CFPAC-1 human pancreatic cancer cells. Using ELISA, flow cytometry, immunoprecipitation, mass spectrometry, Western blot and immunohistochemistry, we found that the target antigens recognised by the two novel mAbs KU44.22B and KU44.13A, are integrin α3 and CD26 respectively, with high levels of expression in human pancreatic and other cancer cell lines and human pancreatic cancer tissue microarrays. Treatment with naked anti-CD26 mAb KU44.13A did not have any effect on the growth and migration of cancer cells nor did it induce receptor downregulation. In contrast, treatment with anti-integrin α3 mAb KU44.22B inhibited growth in vitro of Capan-2 cells, increased migration of BxPC-3 and CFPAC-1 cells and induced antibody internalisation. Both novel mAbs are capable of detecting their target antigens by immunohistochemistry but not by Western blot. These antibodies are excellent tools for studying the role of integrin α3 and CD26 in the complex biology of pancreatic cancer, their prognostic and predictive values and the therapeutic potential of their humanised and/or conjugated versions in patients whose tumours overexpress integrin α3 or CD26. Pancreatic cancer remains one of the deadliest cancer types. In 2018, there were an estimated 458,918 new cases of pancreatic cancer, and 432,242 deaths as a result of pancreatic cancer in 185 countries worldwide 1,2. Pancreatic cancer is predicted to become the second leading cause of cancer death after lung cancer, within the next decade in Western countries 3. At present, the only curative treatment for patients with pancreatic cancer is surgery. However, only a minority of patients are eligible for resection and disease recurrence is a frequent event in many such patients. Historically, gemcitabine-based therapy has been the mainstay for treatment of pancreatic cancer 4. More recently the combination of gemcitabine plus capecitabine has been regarded as the new standard of care in the adjuvant setting 5. Patients with metastatic disease are treated with either FOLFIRINOX or gemcitabine plus nab-paclitaxel as first-line in patients with good performance status 6,7. In order to reduce the dismal pancreatic cancer mortality rates, it is essential to discover novel biomarkers for use in the early detection of pancreatic cancer, to discover novel therapeutic targets and to develop novel and more effective therapeutic agents 8,9. Monoclonal antibodies (mAbs) are excellent tools for the discovery of novel overexpressed cell surface antigens and their specific targeting for diagnostic and therapeutic purposes 10,11. To date, 36 mAbs have been approved for cancer treatment in the U.S. and/or European Union, although none for pancreatic cancer yet 12,13. As tumour heterogeneity has been reported both between (i.e. inter-tumour heterogeneity)

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Genetic and Immunohistochemical Expression of Integrins ITGAV, ITGA6, and ITGA3 As Prognostic Factor for Colorectal Cancer: Models for Global and Disease-Free Survival

Cited by 31 publications

References 30 publications

STROBE-compliant integrin through focal adhesion involve in cancer stem cell and multidrug resistance of ovarian cancer

STROBE-compliant integrin through focal adhesion involve in cancer stem cell and multidrug resistance of ovarian cancer

The Open Chromatin Landscape of Non–Small Cell Lung Carcinoma

Development and application of two novel monoclonal antibodies against overexpressed CD26 and integrin α3 in human pancreatic cancer

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