Influences of AMY1 gene copy number and protein expression on salivary alpha-amylase activity before and after citric acid stimulation in splenic asthenia children

PurposeThe purpose of this study was to characterize insulin-like growth factor-1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non–small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis.Patients and MethodsOne hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n = 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh-frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n = 181).ResultsIGF1R IHC score was higher in squamous cell carcinomas versus other histologies (P < .001) and associated with stage (P = .03) but not survival (P = .46). IGF1R and EGFR protein expression showed significant correlation (r = 0.30; P < .001). IGF1R gene expression by qRT-PCR was higher in squamous cell versus other histologies (P = .006) and did not associate with other clinical features nor survival (P = .73). Employing criteria previously established for EGFR copy number, patients with IGF1R amplification/high polysomy (n = 48; 27%) had 3-year survival of 58%, patients with low polysomy (n = 87; 48%) had 3-year survival of 47% and patients with trisomy/disomy (n = 46; 25%) had 3-year survival of 35%, respectively (P = .024). Prognostic value of high IGF1R gene copy number was confirmed in multivariate analysis.ConclusionIGF1R protein expression is higher in squamous cell versus other histologies and correlates with EGFR expression. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value.

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Altered Salivary Alpha-Amylase Secretion in Patients with Ulcerative Colitis

Gastroenterology Research and Practice ◽

10.1155/2018/4203737 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Zhuoni Xu ◽

Baoping Wei ◽

Yanting Qiu ◽

Tao Zhang

Keyword(s):

Ulcerative Colitis ◽

Nervous System ◽

Copy Number ◽

Nervous Activity ◽

Alpha Amylase ◽

Gene Copy ◽

Anxiety And Depression ◽

Amylase Secretion ◽

Salivary Alpha Amylase ◽

Sympathetic Nervous

Purpose. Patients with ulcerative colitis (UC) frequently present with psychological disturbances as well as dysfunctions of autonomic nervous system (ANS). Salivary alpha-amylase (sAA) secretion is predominantly controlled by sympathetic nervous activity, while salivary fluid secretion is by parasympathetic nervous activity. Thus, it is speculated that alterations of salivary secretion may be addressed in UC populations. Methods. Thirty-five UC patients as well as 32 age- and sex-matched healthy controls were enrolled. Saliva samples before and after citric acid stimulation were collected from each participant, and salivary flow rate (SFR) was calculated accordingly. Western blotting and quantitative PCR were applied to measure the sAA level and sAA gene (AMY1) copy number, respectively. The psychological disorders, anxiety and depression, were evaluated by the scoring system of Hospital Anxiety and Depression Scale (HADS) for each participant. Results. We observed robustly increased prevalence of anxiety (p<0.001) as well as depression (p<0.001) in UC patients relative to controls. Interestingly, we detected elevated basal (p=0.015) and stimulated (p=0.021) sAA levels in the UC populations compared to controls. However, no differences were found for basal (p=0.643) or stimulated (p=0.402) SFR between the two study groups. Besides, AMY1 gene copy number was comparable between UC patients and controls. Conclusions. Our results reveal an overactivity of the sympathetic nervous system and a normal activity of the parasympathetic nervous system in the UC population.

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Gene copy number of epidermal growth factor receptor (EGFR) by fluorescent in situ hybridization (FISH) in head and neck squamous cell carcinomas (HNSCC) is closely correlated with EGFR protein levels assessed by automated quantitative protein analysis (AQUA)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.6023 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 6023-6023

Author(s):

P. Weinberger ◽

A. Psyrri ◽

P. Kountourakis ◽

T. Rampias ◽

C. Sasaki ◽

...

Keyword(s):

In Situ Hybridization ◽

Protein Expression ◽

Protein Content ◽

Gene Amplification ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Egfr Gene ◽

Protein Levels

6023 Background: EGFR overexpression correlates with recurrence and with treatment resistance in HNSCC. The mechanisms of EGFR protein overexpression are poorly understood. Nonetheless, previous investigators have not demonstrated a correlation between EGFR gene copy number and protein content, using conventional immunohistochemistry (IHC). The aim of this study was to evaluate the relationship of EGFR gene copy number and protein expression utilizing fluorescence in situ hybridization (FISH) and AQUA, a novel, immunohistochemical method of automated quantitative in situ proteomic analysis which permits subcellular localization. Methods: A tissue microarray composed of 137 HNSCC treated with (chemo)radiation was constructed and analyzed for EGFR copy number by FISH (Vysis/Abbot) and EGFR protein expression (DAKO antibody) using AQUA analysis of EGFR staining scored on a scale of 0–255 and by conventional IHC. Agreement was assessed using kappa. Results: Sixteen (15%) of one-hundred six tumors with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH+). AQUA demonstrated a range of 3.6–102.2; protein levels assessed by AQUA in the FISH amplified cases were significantly higher (p =0.008) than in the FISH non- amplified ones. Using the EGFR 75th percentile as a cut-off, AQUA and FISH showed significant agreement (percentage of overall agreement 82%, kappa=0.458, p=0.003). To the contrary there was no concordance between FISH and conventional IHC results in this series. Conclusions: The discrepancy between EGFR gene amplification rate and protein expression by IHC reported previously may be due to the limitations and nonquantitative nature of conventional IHC. EGFR protein content correlates with gene copy number if protein content is quantitated and automatically analyzed, as with AQUA. No significant financial relationships to disclose.

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Protein expression (PE) and increased IGF1R gene copy number (GCN) in small cell lung cancer (SCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.10584 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 10584-10584

Author(s):

A. Badzio ◽

M. W. Wynes ◽

R. Dziadziuszko ◽

D. Merrick ◽

M. Pardo ◽

...

Keyword(s):

Lung Cancer ◽

Protein Expression ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Copy Number ◽

Gene Copy Number ◽

Small Cell ◽

Gene Copy ◽

Small Cell Lung

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Androgen Receptor Gene Copy Number and Protein Expression in Treatment-Naïve Prostate Cancer

Urologia Internationalis ◽

10.1159/000455158 ◽

2017 ◽

Vol 99 (2) ◽

pp. 222-228 ◽

Cited By ~ 2

Author(s):

Filip Poelaert ◽

Candy Kumps ◽

Nicolaas Lumen ◽

Stephanie Verschuere ◽

Louis Libbrecht ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Protein Expression ◽

Copy Number ◽

Receptor Gene ◽

Gene Copy Number ◽

Androgen Receptor Gene ◽

Gene Copy ◽

Treatment Naïve

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Prognostic Value of MET Gene Copy Number and Protein Expression in Patients with Surgically Resected Non-Small Cell Lung Cancer: A Meta-Analysis of Published Literatures

PLoS ONE ◽

10.1371/journal.pone.0099399 ◽

2014 ◽

Vol 9 (6) ◽

pp. e99399 ◽

Cited By ~ 41

Author(s):

Baoping Guo ◽

Hong Cen ◽

Xiaohong Tan ◽

Wenjian Liu ◽

Qing Ke

Keyword(s):

Lung Cancer ◽

Protein Expression ◽

Small Cell Lung Cancer ◽

Copy Number ◽

Prognostic Value ◽

Meta Analysis ◽

Gene Copy Number ◽

Small Cell ◽

Gene Copy ◽

Small Cell Lung

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Role of EGFR but not HER2 or HER3 gene copy number in predicting sensitivity of head and neck squamous cell carcinoma (SCCHN) cell lines to EGFR tyrosine kinase inhibitors

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.6063 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 6063-6063

Author(s):

M. Varella-Garcia ◽

K. Acheson ◽

G. B. Marshall ◽

R. M. McCormack ◽

A. Ryan ◽

...

Keyword(s):

Protein Expression ◽

Cell Lines ◽

Copy Number ◽

Kinase Inhibitors ◽

Gene Copy Number ◽

Gene Copy ◽

Sensitive Cell ◽

Egfr Gene ◽

Egfr Tyrosine Kinase Inhibitors ◽

Egfr Tkis

6063 Background: EGFR gene copy number has previously been reported to predict for improved overall survival in NSCLC patients treated with gefitinib (IRESSA) or erlotinib compared with placebo [JCO 2006;24:5034–42 & N Engl J Med 2005;353:133–44]. The utility of EGFR gene copy number as a predictive biomarker in other tumour types such as squamous cell carcinoma of the head and neck (SCCHN) is currently under clinical investigation. The present study examined a panel of 20 SCCHN cell lines to identify potential biomarkers predicting in vitro sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Methods: A panel of 20 SCCHN cell lines was screened for sensitivity to gefitinib, vandetanib or erlotinib using a viable cell number endpoint, with G150 values determined for each cell line (inhibitor concentration required to give 50% growth inhibition). Cell lines were blinded and assessed for EGFR, HER2 and HER3 protein expression by ELISA, mutation status by dye-terminator sequencing, and gene copy number by fluorescence in situ hybridisation (FISH). Results: A broad range in sensitivity was observed for all compounds across the panel of 20 SCCHN cell lines (G150 ranging from 0.001uM to =10uM). 12 cell lines were positive for EGFR genomic gain. Sensitivity (GI50 <1uM) to all EGFR TKIs was seen in 11 lines and resistance (GI50 >8uM) in 5 lines. Of the sensitive cell lines, 9 were positive for EGFR genomic gain compared with only 1 of the resistant lines. Furthermore, EGFR protein expression also had a direct association with EGFR TKI sensitivity. In contrast, only 4 cell lines were positive for HER2 or HER3 genomic gain and there was no correlation with sensitivity. The most sensitive cell line was positive for EGFR genomic gain and was the only line to have an EGFR TK mutation (S768I in exon 20). Conclusions: EGFR gene copy number and protein expression appeared to have predictive value in identifying SCCHN cell lines sensitive to EGFR TKIs. No significant financial relationships to disclose.

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