Dermatopontin: A potential predictor for metastasis of human oral cancer

Yamatoji, Masanobu; Kasamatsu, Atsushi; Kouzu, Yukinao; Koike, Hirofumi; Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

doi:10.1002/ijc.26328

Cited by 71 publications

(62 citation statements)

References 30 publications

(30 reference statements)

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“…Down-regulation of cell adhesion related proteins (e.g. NCAM1, NCAM2, CADM1 and DPT) have been associated with more aggressive tumors and suggests that the poorly differentiated SqCC tumor may have increased mobility, invasive capacity and poor prognosis [42–44]. Another set of tumor associated down-regulated proteins that drew our attention was related to inflammatory response and wound healing (e.g.…”

Section: Resultsmentioning

confidence: 99%

Quantitative Proteomic Analysis of Optimal Cutting Temperature (OCT) Embedded Core-Needle Biopsy of Lung Cancer

Zhao

Huffman

Fujimoto

et al. 2017

J. Am. Soc. Mass Spectrom.

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With recent advances in understanding the genomic underpinnings and oncogenic drivers of pathogenesis in different subtypes, it is increasingly clear that proper pre-treatment diagnostics are essential for the choice of appropriate treatment options for non-small cell lung cancer (NSCLC). Tumor tissue preservation in optimal cutting temperature (OCT) compound is commonly used in the surgical suite. However, proteins recovered from OCT embedded specimens pose a challenge for LC-MS/MS experiments, due to the large amounts of polymers present in OCT. Here we present a simple workflow for whole proteome analysis of OCT-embedded NSCLC tissue samples, which involves a simple trichloroacetic acid precipitation step. Comparisons of protein recovery between frozen versus OCT embedded tissue showed excellent consistency with more than 9,200 proteins identified. Using an isobaric labeling strategy, we quantified more than 5,400 proteins in tumor versus normal OCT-embedded core needle biopsy samples. Gene Ontology analysis indicated that a number of proliferative as well as SqCC (squamous cell carcinoma) marker proteins were overexpressed in the tumor, consistent with the patient’s pathology based diagnosis of “poorly differentiated SqCC”. Among the most downregulated proteins in the tumor sample, we noted a number of proteins with potential immunomodulatory functions. Finally, interrogation of the aberrantly expressed proteins using a candidate approach and cross-referencing with publically available databases led to the identification of potential druggable targets in DNA replication and DNA damage repair pathways. We conclude that our approach allows LC-MS/MS proteomic analyses on OCT-embedded lung cancer specimens, opening the way to bring powerful proteomics into the clinic.

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Section: Resultsmentioning

confidence: 99%

Quantitative Proteomic Analysis of Optimal Cutting Temperature (OCT) Embedded Core-Needle Biopsy of Lung Cancer

Zhao

Huffman

Fujimoto

et al. 2017

J. Am. Soc. Mass Spectrom.

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“…The slides were then lightly counterstained with hematoxylin, dehydrated with ethanol, cleaned with xylene and mounted. To quantify the state of FHL1 protein expression in those components, we used IHC score systems described previously (18,(22)(23)(24)(25)(26)(27)(28)(29)(30). Briefly, the stained cells were determined in at least five random fields at magnification x400 in each section.…”

Section: Methodsmentioning

confidence: 99%

High prevalence of epigenetic inactivation of the human four and a half LIM domains 1 gene in human oral cancer

Koike

Kasamatsu

Iyoda

et al. 2012

International Journal of Oncology

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Abstract.The four and a half LIM domains 1 (FHL1) gene has been related to carcinogenesis. However, the expression status of FHL1 in human oral squamous cell carcinoma (OSCC) remains unclear and the detailed mechanism of gene silencing is poorly understood. The aim of this study was to examine the FHL1 expression level and its regulatory mechanism in OSCCs. Quantitative reverse-transcriptase-polymerase chain reaction (PCR) and western blotting showed significant downregulation of FHL1 in all OSCC-derived cell lines (Sa3, HSC-2, HSC-3, HSC-4, HO-1-u-1, HO-1-N-1, KON and Ca9-22) compared to human normal oral keratinocytes. We also found that FHL1 mRNA expression was frequently downregulated (P<0.01) in 51 (86.4%) of 59 primary OSCCs compared with the corresponding normal oral tissues, while there was no significant difference between the status of the FHL1 protein expression in OSCCs and the clinicopathological features. Using methylationspecific PCR, we detected methylated FHL1 in all cell lines and treatment with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine restored the FHL1 expression. However, no significant restoration of FHL1 expression was observed using sodium butyrate, an inhibitor of histone deacetylase and chromatin immunoprecipitation showed that histone H3 lysine 9 in the FHL1 promoter region was significantly acetylated. In addition, no mutation in the entire coding region of the FHL1 gene was found. Therefore, our data suggested that inactivation of the FHL1 gene is a frequent event during oral carcinogenesis and that the mechanism of FHL1 downregulation in OSCCs is through DNA methylation of the promoter region rather than histone deacetylation or mutation. IntroductionHead and neck squamous cell carcinoma (HNSCC) is one of the most frequently occurring malignancies and a major cause of morbidity and mortality (1,2). Oral cancer is the most common among the HNSCCs and the most frequently occurring oral cancer is squamous cell carcinoma (OSCC), which accounts for more than 90% of all oral malignancies (3). The number of OSCC cases that occur worldwide annually exceeds 300,000 (4). The mechanisms behind tumor progression of OSCC are known to a limited extent, indicating a clear need for comprehensive knowledge that can lead to more specific and effective molecular target.Microarray technology facilitates simultaneous evaluation of thousands of genes in a specimen. The results of microarray analysis provide researchers with high throughput screening to study the roles played by specific genes in cancer development and progression. We previously reported gene expression profiling of OSCC to identify cancer-related genes (5,6).The four and a half LIM domains (FHL) family of genes is characterized by LIM domains, a term derived from the first letters of three transcription factors: Lin-11, Isl-1 and Mec-3. Because the LIM domains provide protein-protein binding interfaces, the FHL genes play an important role in cellular events such as focal adhesion and differentiation by repressing or ac...

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“…However, the 5-year relative survival rate of distant metastasis of oral cavity and pharynx cancer is approximately 30-40% [1,5]. To improve the survival rates of oral cancer patients through metastasis prevention, the discovery of novel tumor biomarkers for early diagnosis is essential [6][7][8].…”

Section: Introductionmentioning

confidence: 99%