Membrane Proteome of Invasive Retinoblastoma: Differential Proteins and Biomarkers

Danda, Ravikanth; Ganapathy, Kalaivani; Sathe, Gajanan; Madugundu, Anil K.; Krishnan, Uma Maheswari; Khetan, Vikas; Rishi, Pukhraj; Gowda, Harsha; Pandey, Akhilesh; Krishnakumar, Subramanian; Prasad, T. S. Keshava; Elchuri, Sailaja

doi:10.1002/prca.201700101

Cited by 16 publications

(13 citation statements)

References 27 publications

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“…In addition, the silencing of LMNB1 impaired tumorigenicity, tumor invasion, and cell proliferation in pancreatic cancer cells [36]. Additionally, the overexpression of LMNB1 was the biomarker indicating the occurrence of retinoblastomas and poor prognosis of colon cancers [35,37]. e relationship between LMNB1 and LUAD has not been observed previously and LMNB1 might be a promising predictive biomarker and molecular target.…”

Section: Discussionmentioning

confidence: 90%

Identifying Tumorigenesis and Prognosis-Related Genes of Lung Adenocarcinoma: Based on Weighted Gene Coexpression Network Analysis

Qin

et al. 2020

BioMed Research International

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Lung adenocarcinoma is the most frequently diagnosed subtype of nonsmall cell lung cancer. The molecular mechanisms of the initiation and progression of lung adenocarcinoma remain to be further determined. This study aimed to screen genes related to the progression of lung adenocarcinoma. By weighted gene coexpression network analysis (WGCNA), we constructed a free-scale gene coexpression network to evaluate the correlations between multiple gene sets and patients’ clinical traits, then further identify predictive biomarkers. GSE11969 was obtained from the Gene Expression Omnibus (GEO) database which contained the gene expression data of 90 lung adenocarcinoma patients. Data of the Cancer Genome Atlas (TCGA) were employed as the validation cohort. After the average linkage hierarchical clustering, a total of 9 modules were generated. In the clinical significant module (R = 0.44, P<0.0001), we identified 29 network hub genes. Subsequent verification in the TCGA database showed that 11 hub genes (ANLN, CDCA5, FLJ21924, LMNB1, MAD2L1, RACGAP1, RFC4, SNRPD1, TOP2A, TTK, and ZWINT) were significantly associated with poor survival data of lung adenocarcinomas. Besides, the results of receiver operating characteristic curves indicated that the mRNA levels of this group of genes exhibited high specificity and sensitivity to distinguish malignant lesions from nonmalignant tissues. Apart from mRNA levels, we found that the protein abundances of these 11 genes were remarkably upregulated in lung adenocarcinomas compared with normal tissues. In conclusion, by the WGCNA method, a panel of 11 genes were identified as predictive biomarkers for tumorigenesis and poor prognosis of lung adenocarcinomas.

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Section: Discussionmentioning

confidence: 90%

Identifying Tumorigenesis and Prognosis-Related Genes of Lung Adenocarcinoma: Based on Weighted Gene Coexpression Network Analysis

Qin

et al. 2020

BioMed Research International

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“…In this study, we analyzed the expression of B7H3 in primary retinoblastoma tissues by immunohistochemistry for two reasons. (i) Our earlier study on proteomics of RB revealed significant expression of B7H3 in primary RB tumor samples compared to normal retina 7 , and, (ii) Definitive role of B7H3 in immune evasion of tumor cells by inhibiting T cell functions.…”

Section: Discussionmentioning

confidence: 97%

“…We had earlier performed a membrane proteomics comparing primary retinoblastoma and retinal tissue 7 . While comparing their expression for immunotherapy molecules we found B7-H3 (CD276); one of the B7 family checkpoint molecule to be overexpressed in RB tumor compared to the retinal tissue.…”

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confidence: 99%

Clinical relevance of B7H3 expression in retinoblastoma

Ganesan

Parameswaran²,

Sharma

et al. 2020

Sci Rep

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Retinoblastoma (RB) is the most common paediatric intraocular tumour. currently, chemotherapy is widely used to reduce the chance of metastasis as well as for vision salvage. the limitations of chemotherapy for RB include chemoresistance and cytotoxicity. Recently, immunotherapy is considered for treating chemoresistant cancers. Although, several molecular targets are available for immunotherapy in different cancers, we were interested in B7H3, as it was differentially expressed between retinoblastoma and retina in our earlier proteomics study. Hence, in this study we validated the previous finding by Western blotting and immunohistochemistry on primary RB tumor samples. The results suggest significantly increased expression of B7H3 in RB tumor samples compared to retina by western blotting. immunohistochemistry revealed spatial, inter and intratumoral heterogeneity in the primary RB tumor sections. Correlation of the B7H3 expression with clinical and histopathological data revealed significantly increased expression of B7H3 in poorly differentiated, non-neural invasive tumors and lower expression in neural invasion and severe anaplastic areas of the tumors. B7H3 expression did not significantly vary between low-risk and high-risk tumors. The study also revealed considerably reduced infiltration of T lymphocytes in RB. We conclude that B7H3 is prominently expressed in primary RB tumors and could be used for targeted therapy.

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“…Three microarray, gene expression datasets (GSE24673, 14 GSE97508, 15 and GSE110811 16 ) were retrieved from the Gene Expression Omnibus (GEO) database (https://www. ncbi.nlm.nih.gov/geo/).…”

Section: Data Sourcesmentioning

confidence: 99%

TRIM59 Promotes Retinoblastoma Progression by Activating the p38–MAPK Signaling Pathway

Shang

You

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Retinoblastoma is a malignant tumor of the developing retina that mostly occurs in children. Our study aimed to investigate the effect of tripartite motif-containing protein 59 (TRIM59) on retinoblastoma growth and the underlying mechanisms. METHODS. We performed bioinformatic analysis of three datasets (GSE24673, GSE97508, and GSE110811) from the Gene Expression Omnibus database. Quantitative reversetranscription PCR and immunoblotting of three retinoblastoma cell lines were conducted to verify TRIM59 as a differentially expressed gene. Specific siRNAs were used to inhibit TRIM59 expression in the HXO-Rb44 cell line. A lentiviral vector was transfected into the Y79 cell line to overexpress TRIM59. The effects of TRIM59 on retinoblastoma cell proliferation, cell cycling, and apoptosis were explored in vitro using the abovementioned cell lines. The effect of TRIM59 expression on retinoblastoma cell proliferation was evaluated in a mouse xenograft tumor model. RESULTS. TRIM59 expression in three retinoblastoma cell lines was remarkably elevated compared with normal control. Knocking down TRIM59 expression remarkably suppressed cell proliferation and growth and promoted cell apoptosis in HXO-Rb44 cells, whereas TRIM59 overexpression promoted tumor progression in Y79 cells. Silencing TRIM59 also markedly inhibited in vivo tumor growth in the xenograft model. Mechanistic studies revealed that TRIM59 upregulated phosphorylated p38, p-JNK1/2, p-ERK1/2, and p-c-JUN expression in retinoblastoma cells. Notably, the p38 inhibitor SB203580 attenuated the effects of TRIM59 on cell proliferation, apoptosis, and the G 1 /S phase transition. CONCLUSIONS. TRIM59 plays an oncogenic role in retinoblastoma and exerts its tumorpromotive function by activating the p38-mitogen-activated protein kinase pathway.

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Membrane Proteome of Invasive Retinoblastoma: Differential Proteins and Biomarkers

Abstract: The present study, is the first comprehensive quantitative membrane proteomic atlas of the differentially regulated proteins in RB compared to the retina. LMNB1 and TFRC could be potential biomarkers for this childhood cancer.

Cited by 16 publications

References 27 publications

Identifying Tumorigenesis and Prognosis-Related Genes of Lung Adenocarcinoma: Based on Weighted Gene Coexpression Network Analysis

Identifying Tumorigenesis and Prognosis-Related Genes of Lung Adenocarcinoma: Based on Weighted Gene Coexpression Network Analysis

Clinical relevance of B7H3 expression in retinoblastoma

TRIM59 Promotes Retinoblastoma Progression by Activating the p38–MAPK Signaling Pathway

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