Human neutrophil peptides 1-3 as gastric cancer tissue markers measured by MALDI-imaging mass spectrometry

Implications for infiltrated neutrophils as a tumor target

Chun Chia Cheng, Jungshan Chang, Ling Yun Chen, Ai Sheng Ho, Ker Jer Huang, Shui Cheng Lee, Fu Der Mai, Chun Chao Chang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objective: Human neutrophil peptides (HNPs)-1,-2 and-3 are significantly upregulated and were reported as biomarkers in gastric cancer (GC). However, the tissue location and function of HNPs 1-3 are still unclear in GC, and the spatial distribution of the triad needs to be disclosed. The aims of this study were to investigate the distribution and relationships among HNPs-1,-2 and-3, and assess whether infiltrated neutrophils accumulate in gastric tumor. Methods: In this study, paired samples (n=33) of the GC tissues and adjacent normal tissues from the same patients were obtained from surgery. Expression of HNPs 1-3 were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The distributions of the HNPs 1-3 in GC tissues were investigated. After verification of HNPs-1 by immunohistochemistry, infiltrated neutrophils were also detected. Then, an in vitro assay was used to observe the binding capacity and measure the cytotoxic effect of HNPs-1 against AGS cells. Results: Comparing to neighboring normal tissue, expressional level of HNPs 1-3 were significantly higher and their distributions overlapped in cancerous tissues of GC patients with high abundance in the lamina propria, whereas HNPs-1 was identified as the highest major peak. Moreover, HNPs-1,-2 and-3 correlated with each other. Besides, we also observed that increased infiltrated neutrophils accumulating in GC tissues, indicating that a strong positive correlation between HNPs 1-3 and infiltrated neutrophils. In addition, the further investigated demonstrated that the major peptide, HNPs-1, was statistically increased with the advance of tumor development from the early to advanced stage of GC (p<0.05). Moreover, we also noticed that HNPs-1 with a great binding capacity to GC AGS cells in vitro can inhibit tumor cell growth. Conclusions: Our results suggest that neutrophil secreted peptides, HNPs 1-3, increased in the GC tissues and could be used as potential biomarkers detected using MALDI-TOF MS, implying that elevated neutrophils may be used as a tumor target for tumor treatment. The binding capacity of HNPs-1 with GC cells implies that tracking molecules conjugated with HNPs-1 could be applied as a specific probe for GC diagnoses.

Original languageEnglish
Pages (from-to)21-31
Number of pages11
JournalDisease Markers
Volume32
Issue number1
DOIs
Publication statusPublished - 2012

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Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Stomach Neoplasms
Mass spectrometry
Tumors
Mass Spectrometry
Neutrophils
Tissue
Imaging techniques
Neoplasms
human neutrophil peptide 3
human neutrophil peptide 1
Biomarkers
Ionization
Desorption
Lasers
Cell Tracking
Peptides
Cell growth
Surgery
Spatial distribution

Keywords

  • biomarker
  • Gastric cancer
  • human neutrophil peptides 1-3
  • MALDI-TOF MS

ASJC Scopus subject areas

  • Biochemistry, medical
  • Clinical Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Human neutrophil peptides 1-3 as gastric cancer tissue markers measured by MALDI-imaging mass spectrometry : Implications for infiltrated neutrophils as a tumor target. / Cheng, Chun Chia; Chang, Jungshan; Chen, Ling Yun; Ho, Ai Sheng; Huang, Ker Jer; Lee, Shui Cheng; Mai, Fu Der; Chang, Chun Chao.

In: Disease Markers, Vol. 32, No. 1, 2012, p. 21-31.

Research output: Contribution to journalArticle

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abstract = "Objective: Human neutrophil peptides (HNPs)-1,-2 and-3 are significantly upregulated and were reported as biomarkers in gastric cancer (GC). However, the tissue location and function of HNPs 1-3 are still unclear in GC, and the spatial distribution of the triad needs to be disclosed. The aims of this study were to investigate the distribution and relationships among HNPs-1,-2 and-3, and assess whether infiltrated neutrophils accumulate in gastric tumor. Methods: In this study, paired samples (n=33) of the GC tissues and adjacent normal tissues from the same patients were obtained from surgery. Expression of HNPs 1-3 were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The distributions of the HNPs 1-3 in GC tissues were investigated. After verification of HNPs-1 by immunohistochemistry, infiltrated neutrophils were also detected. Then, an in vitro assay was used to observe the binding capacity and measure the cytotoxic effect of HNPs-1 against AGS cells. Results: Comparing to neighboring normal tissue, expressional level of HNPs 1-3 were significantly higher and their distributions overlapped in cancerous tissues of GC patients with high abundance in the lamina propria, whereas HNPs-1 was identified as the highest major peak. Moreover, HNPs-1,-2 and-3 correlated with each other. Besides, we also observed that increased infiltrated neutrophils accumulating in GC tissues, indicating that a strong positive correlation between HNPs 1-3 and infiltrated neutrophils. In addition, the further investigated demonstrated that the major peptide, HNPs-1, was statistically increased with the advance of tumor development from the early to advanced stage of GC (p<0.05). Moreover, we also noticed that HNPs-1 with a great binding capacity to GC AGS cells in vitro can inhibit tumor cell growth. Conclusions: Our results suggest that neutrophil secreted peptides, HNPs 1-3, increased in the GC tissues and could be used as potential biomarkers detected using MALDI-TOF MS, implying that elevated neutrophils may be used as a tumor target for tumor treatment. The binding capacity of HNPs-1 with GC cells implies that tracking molecules conjugated with HNPs-1 could be applied as a specific probe for GC diagnoses.",
keywords = "biomarker, Gastric cancer, human neutrophil peptides 1-3, MALDI-TOF MS",
author = "Cheng, {Chun Chia} and Jungshan Chang and Chen, {Ling Yun} and Ho, {Ai Sheng} and Huang, {Ker Jer} and Lee, {Shui Cheng} and Mai, {Fu Der} and Chang, {Chun Chao}",
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T1 - Human neutrophil peptides 1-3 as gastric cancer tissue markers measured by MALDI-imaging mass spectrometry

T2 - Implications for infiltrated neutrophils as a tumor target

AU - Cheng, Chun Chia

AU - Chang, Jungshan

AU - Chen, Ling Yun

AU - Ho, Ai Sheng

AU - Huang, Ker Jer

AU - Lee, Shui Cheng

AU - Mai, Fu Der

AU - Chang, Chun Chao

PY - 2012

Y1 - 2012

N2 - Objective: Human neutrophil peptides (HNPs)-1,-2 and-3 are significantly upregulated and were reported as biomarkers in gastric cancer (GC). However, the tissue location and function of HNPs 1-3 are still unclear in GC, and the spatial distribution of the triad needs to be disclosed. The aims of this study were to investigate the distribution and relationships among HNPs-1,-2 and-3, and assess whether infiltrated neutrophils accumulate in gastric tumor. Methods: In this study, paired samples (n=33) of the GC tissues and adjacent normal tissues from the same patients were obtained from surgery. Expression of HNPs 1-3 were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The distributions of the HNPs 1-3 in GC tissues were investigated. After verification of HNPs-1 by immunohistochemistry, infiltrated neutrophils were also detected. Then, an in vitro assay was used to observe the binding capacity and measure the cytotoxic effect of HNPs-1 against AGS cells. Results: Comparing to neighboring normal tissue, expressional level of HNPs 1-3 were significantly higher and their distributions overlapped in cancerous tissues of GC patients with high abundance in the lamina propria, whereas HNPs-1 was identified as the highest major peak. Moreover, HNPs-1,-2 and-3 correlated with each other. Besides, we also observed that increased infiltrated neutrophils accumulating in GC tissues, indicating that a strong positive correlation between HNPs 1-3 and infiltrated neutrophils. In addition, the further investigated demonstrated that the major peptide, HNPs-1, was statistically increased with the advance of tumor development from the early to advanced stage of GC (p<0.05). Moreover, we also noticed that HNPs-1 with a great binding capacity to GC AGS cells in vitro can inhibit tumor cell growth. Conclusions: Our results suggest that neutrophil secreted peptides, HNPs 1-3, increased in the GC tissues and could be used as potential biomarkers detected using MALDI-TOF MS, implying that elevated neutrophils may be used as a tumor target for tumor treatment. The binding capacity of HNPs-1 with GC cells implies that tracking molecules conjugated with HNPs-1 could be applied as a specific probe for GC diagnoses.

AB - Objective: Human neutrophil peptides (HNPs)-1,-2 and-3 are significantly upregulated and were reported as biomarkers in gastric cancer (GC). However, the tissue location and function of HNPs 1-3 are still unclear in GC, and the spatial distribution of the triad needs to be disclosed. The aims of this study were to investigate the distribution and relationships among HNPs-1,-2 and-3, and assess whether infiltrated neutrophils accumulate in gastric tumor. Methods: In this study, paired samples (n=33) of the GC tissues and adjacent normal tissues from the same patients were obtained from surgery. Expression of HNPs 1-3 were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The distributions of the HNPs 1-3 in GC tissues were investigated. After verification of HNPs-1 by immunohistochemistry, infiltrated neutrophils were also detected. Then, an in vitro assay was used to observe the binding capacity and measure the cytotoxic effect of HNPs-1 against AGS cells. Results: Comparing to neighboring normal tissue, expressional level of HNPs 1-3 were significantly higher and their distributions overlapped in cancerous tissues of GC patients with high abundance in the lamina propria, whereas HNPs-1 was identified as the highest major peak. Moreover, HNPs-1,-2 and-3 correlated with each other. Besides, we also observed that increased infiltrated neutrophils accumulating in GC tissues, indicating that a strong positive correlation between HNPs 1-3 and infiltrated neutrophils. In addition, the further investigated demonstrated that the major peptide, HNPs-1, was statistically increased with the advance of tumor development from the early to advanced stage of GC (p<0.05). Moreover, we also noticed that HNPs-1 with a great binding capacity to GC AGS cells in vitro can inhibit tumor cell growth. Conclusions: Our results suggest that neutrophil secreted peptides, HNPs 1-3, increased in the GC tissues and could be used as potential biomarkers detected using MALDI-TOF MS, implying that elevated neutrophils may be used as a tumor target for tumor treatment. The binding capacity of HNPs-1 with GC cells implies that tracking molecules conjugated with HNPs-1 could be applied as a specific probe for GC diagnoses.

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KW - MALDI-TOF MS

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