Dataset Information

LRP6 is identified as a potential prognostic marker for oral squamous cell carcinoma via MALDI-IMS.

ABSTRACT: Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide, with 500?000 new cases each year. However, the mechanisms underlying OSCC development are relatively unknown. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was used to profile the differentially expressed peptides/proteins between OSCC tissues and their adjacent noncancerous tissues. Sixty-seven unique peptide peaks and five distinct proteins were identified with changed expression levels. Among them, LRP6 expression was found to be upregulated in OSCC tissues, and correlated with a cluster of clinicopathologic parameters, including smoking, drinking, tumor differentiation status, lymph node metastasis and survival time. Notably, knockdown of LRP6 inhibited the proliferation ability of OSCC cells. Furthermore, we demonstrated that the expression of LRP6 in OSCC cells is positively correlated with its downstream oncogene, FGF8. The present study suggests that LRP6 could be a potential biomarker for OSCC patients, and might further assist in the therapeutic decisions in OSCC treatment.

SUBMITTER: Yuan Y

PROVIDER: S-EPMC5636978 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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LRP6 is identified as a potential prognostic marker for oral squamous cell carcinoma via MALDI-IMS.

Yuan Yao Y Xie Xiaoyan X Jiang Yuchen Y Wei Zihao Z Wang Peiqi P Chen Fangman F Li Xinyi X Sun Chongkui C Zhao Hang H Zeng Xin X Jiang Lu L Zhou Yu Y Dan Hongxia H Feng Mingye M Liu Rui R Wang Zhiyong Z Chen Qianming Q

Cell death & disease 20170907 9

Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide, with 500 000 new cases each year. However, the mechanisms underlying OSCC development are relatively unknown. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was used to profile the differentially expressed peptides/proteins between OSCC tissues and their adjacent noncancerous tissues. Sixty-seven unique peptide peaks and five distin ...[more]

PMID: 28880263

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Project description:BackgroundResistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC). This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC) based AQUAnalysis technique.MethodsSixty-nine OSCC patients diagnosed between 1998-2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model.ResultsBax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS), with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006), in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses, Bax protein expression remained an independent predictor of DSS in OSCC [HR 0.241 (0.078-0.745), p = 0.013].ConclusionsThe AQUA technique used in our study eliminates observer bias and provides reliable and reproducible estimates for biomarker expression. AQUA also provides essential measures of quality control that cannot be achieved with manual biomarker scoring techniques. Our results support the use of Bax protein expression as a prognostic marker in conjunction with other clinico-pathological variables when designing personalized treatment strategies for OSCC patients.

Project description:Background: Oral cancer is a frequently encountered neoplasm of the head and neck region, being the eighth most common type of human malignancy worldwide. Despite improvement in its control, morbidity and mortality, rates have improved little in the past decades. The present investigations about gene interaction and pathways still could not clear the appearance and development of oral squamous cell carcinoma (OSCC), completely. The aim of this study is to investigate the key genes and microRNAs interaction in OSCC. Materials and Methods: The microarray datasets GSE13601 and GSE98463, including mRNA and miRNA profiles, were extracted from the GEO database and were analyzed using GEO2R. Functional and pathway enrichment analyses were performed by using the DAVID database. The protein-protein interaction (PPI) network was constructed and analyzed using STRING database and Cytoscape software, respectively. Finally, miRDB was applied to predict the targets of the differentially expressed miRNAs (DEMs). Results: Totally, 97 differentially expressed genes (DEGs) were found in OSCC, including 66 up-regulated and 31 down-regulated genes. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that up-regulated genes were significantly enriched in movement of cell or subcellular component, cell adhesion, biological adhesion, cellular localization, apoptotic signaling pathway, while the downregulated genes were enriched in muscle system process and oxidation-reduction process. From the PPI network, the top 10 nodes with the highest degree were detected as hub genes. In addition, 18 DEMs were screened, which included 7 up-regulated and 11 down-regulated miRNAs. STAT1 was potentially targeted by three miRNAs, including has-miR- 6825-5P, has-miR-4495, and has-miR-5580-3P. Conclusion: The roles of DEMs such as hsa-mir-5580-3p in OSCC through interactions with DEGs CD44, ACLY, ACTR3, STAT1, LAMC2 and YWHAZ may offer a suitable candidate biomarker pattern for diagnosis, prognosis and treatment processes in OSCC.

Dataset Information

LRP6 is identified as a potential prognostic marker for oral squamous cell carcinoma via MALDI-IMS.

Publications

LRP6 is identified as a potential prognostic marker for oral squamous cell carcinoma via MALDI-IMS.

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