Loss of ZG16 is associated with molecular and clinicopathological phenotypes of colorectal cancer

Hui Meng, Wencai Li, Lisa Allyn Boardman, Liang Wang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Zymogen granule protein 16 (ZG16) is one of the most significantly down-regulated genes in colorectal cancer (CRC) tissues. This study aimed to further evaluate its expression changes and investigate its association with molecular and clinicopathological characteristics of CRC. Methods: We applied quantitative RT-PCR to determine expression difference between tumor and matched normal tissues from 23 CRC patients. To further validate the down-regulation in tumor tissues, we performed immunohistochemistry (IHC) analysis in 40 paraffin-embedded normal-tumor pairs and 22 colon tissues with a variety of diseases. To evaluate if the ZG16 gene changes were associated with clinicopathological characteristics, we further analyzed the gene expression and copy number changes from The Cancer Genome Atlas (TCGA) and Oncomine datasets. Results: Quantitative RT-PCR confirmed significant down-regulation (~ 130-fold) of ZG16 in all tumor tissues. ZG16 expression was in an organ-specific manner with an extremely high expression in normal epithelial cells of small intestine, colon and rectum. IHC analysis showed that ZG16 protein was completely lost in all of 40 CRC tissues, and partially lost in premalignant adenomatous polyps (adenomas) and chronic ulcerative colitis tissues. Gene expression and copy number changes were significantly associated with multiple molecular and clinicopathological features of CRC including microsatellite instability (MSI), MLH1 silencing, CpG island methylator phenotype, hyper-mutation status, gender, presence of synchronous adenomas, and histological type (P < 0.05). Patients with lower ZG16 gene expression showed shorter progression-free survival and overall survival than those with relatively higher expression (P < 0.05). Multivariate analysis suggested that the ZG16 expression was an independent prognosis factor (P = 0.012, HR = 6.286, 95% CI = 0.816-0.975). Conclusion: For the first time, our study demonstrated that ZG16 expression was sequentially reduced from normal, adenoma, to carcinoma. Association with multiple clinicopathological features indicates that ZG16 may play an important role in cancer initiation and progression. ZG16 may serve as a potential biomarker for diagnosis and prognosis of CRC.

Original languageEnglish (US)
Article number433
JournalBMC Cancer
Volume18
Issue number1
DOIs
StatePublished - Apr 16 2018

Fingerprint

Secretory Vesicles
Colorectal Neoplasms
Phenotype
Proteins
Adenoma
Neoplasms
Gene Dosage
Gene Expression
Colon
Down-Regulation
Immunohistochemistry
Adenomatous Polyps
Polymerase Chain Reaction
Microsatellite Instability
CpG Islands
Atlases
Ulcerative Colitis
Rectum
Paraffin
Disease-Free Survival

Keywords

  • Colorectal cancer
  • Copy number variation
  • Gene expression
  • Survival
  • ZG16

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Loss of ZG16 is associated with molecular and clinicopathological phenotypes of colorectal cancer. / Meng, Hui; Li, Wencai; Boardman, Lisa Allyn; Wang, Liang.

In: BMC Cancer, Vol. 18, No. 1, 433, 16.04.2018.

Research output: Contribution to journalArticle

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abstract = "Background: Zymogen granule protein 16 (ZG16) is one of the most significantly down-regulated genes in colorectal cancer (CRC) tissues. This study aimed to further evaluate its expression changes and investigate its association with molecular and clinicopathological characteristics of CRC. Methods: We applied quantitative RT-PCR to determine expression difference between tumor and matched normal tissues from 23 CRC patients. To further validate the down-regulation in tumor tissues, we performed immunohistochemistry (IHC) analysis in 40 paraffin-embedded normal-tumor pairs and 22 colon tissues with a variety of diseases. To evaluate if the ZG16 gene changes were associated with clinicopathological characteristics, we further analyzed the gene expression and copy number changes from The Cancer Genome Atlas (TCGA) and Oncomine datasets. Results: Quantitative RT-PCR confirmed significant down-regulation (~ 130-fold) of ZG16 in all tumor tissues. ZG16 expression was in an organ-specific manner with an extremely high expression in normal epithelial cells of small intestine, colon and rectum. IHC analysis showed that ZG16 protein was completely lost in all of 40 CRC tissues, and partially lost in premalignant adenomatous polyps (adenomas) and chronic ulcerative colitis tissues. Gene expression and copy number changes were significantly associated with multiple molecular and clinicopathological features of CRC including microsatellite instability (MSI), MLH1 silencing, CpG island methylator phenotype, hyper-mutation status, gender, presence of synchronous adenomas, and histological type (P < 0.05). Patients with lower ZG16 gene expression showed shorter progression-free survival and overall survival than those with relatively higher expression (P < 0.05). Multivariate analysis suggested that the ZG16 expression was an independent prognosis factor (P = 0.012, HR = 6.286, 95{\%} CI = 0.816-0.975). Conclusion: For the first time, our study demonstrated that ZG16 expression was sequentially reduced from normal, adenoma, to carcinoma. Association with multiple clinicopathological features indicates that ZG16 may play an important role in cancer initiation and progression. ZG16 may serve as a potential biomarker for diagnosis and prognosis of CRC.",
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N2 - Background: Zymogen granule protein 16 (ZG16) is one of the most significantly down-regulated genes in colorectal cancer (CRC) tissues. This study aimed to further evaluate its expression changes and investigate its association with molecular and clinicopathological characteristics of CRC. Methods: We applied quantitative RT-PCR to determine expression difference between tumor and matched normal tissues from 23 CRC patients. To further validate the down-regulation in tumor tissues, we performed immunohistochemistry (IHC) analysis in 40 paraffin-embedded normal-tumor pairs and 22 colon tissues with a variety of diseases. To evaluate if the ZG16 gene changes were associated with clinicopathological characteristics, we further analyzed the gene expression and copy number changes from The Cancer Genome Atlas (TCGA) and Oncomine datasets. Results: Quantitative RT-PCR confirmed significant down-regulation (~ 130-fold) of ZG16 in all tumor tissues. ZG16 expression was in an organ-specific manner with an extremely high expression in normal epithelial cells of small intestine, colon and rectum. IHC analysis showed that ZG16 protein was completely lost in all of 40 CRC tissues, and partially lost in premalignant adenomatous polyps (adenomas) and chronic ulcerative colitis tissues. Gene expression and copy number changes were significantly associated with multiple molecular and clinicopathological features of CRC including microsatellite instability (MSI), MLH1 silencing, CpG island methylator phenotype, hyper-mutation status, gender, presence of synchronous adenomas, and histological type (P < 0.05). Patients with lower ZG16 gene expression showed shorter progression-free survival and overall survival than those with relatively higher expression (P < 0.05). Multivariate analysis suggested that the ZG16 expression was an independent prognosis factor (P = 0.012, HR = 6.286, 95% CI = 0.816-0.975). Conclusion: For the first time, our study demonstrated that ZG16 expression was sequentially reduced from normal, adenoma, to carcinoma. Association with multiple clinicopathological features indicates that ZG16 may play an important role in cancer initiation and progression. ZG16 may serve as a potential biomarker for diagnosis and prognosis of CRC.

AB - Background: Zymogen granule protein 16 (ZG16) is one of the most significantly down-regulated genes in colorectal cancer (CRC) tissues. This study aimed to further evaluate its expression changes and investigate its association with molecular and clinicopathological characteristics of CRC. Methods: We applied quantitative RT-PCR to determine expression difference between tumor and matched normal tissues from 23 CRC patients. To further validate the down-regulation in tumor tissues, we performed immunohistochemistry (IHC) analysis in 40 paraffin-embedded normal-tumor pairs and 22 colon tissues with a variety of diseases. To evaluate if the ZG16 gene changes were associated with clinicopathological characteristics, we further analyzed the gene expression and copy number changes from The Cancer Genome Atlas (TCGA) and Oncomine datasets. Results: Quantitative RT-PCR confirmed significant down-regulation (~ 130-fold) of ZG16 in all tumor tissues. ZG16 expression was in an organ-specific manner with an extremely high expression in normal epithelial cells of small intestine, colon and rectum. IHC analysis showed that ZG16 protein was completely lost in all of 40 CRC tissues, and partially lost in premalignant adenomatous polyps (adenomas) and chronic ulcerative colitis tissues. Gene expression and copy number changes were significantly associated with multiple molecular and clinicopathological features of CRC including microsatellite instability (MSI), MLH1 silencing, CpG island methylator phenotype, hyper-mutation status, gender, presence of synchronous adenomas, and histological type (P < 0.05). Patients with lower ZG16 gene expression showed shorter progression-free survival and overall survival than those with relatively higher expression (P < 0.05). Multivariate analysis suggested that the ZG16 expression was an independent prognosis factor (P = 0.012, HR = 6.286, 95% CI = 0.816-0.975). Conclusion: For the first time, our study demonstrated that ZG16 expression was sequentially reduced from normal, adenoma, to carcinoma. Association with multiple clinicopathological features indicates that ZG16 may play an important role in cancer initiation and progression. ZG16 may serve as a potential biomarker for diagnosis and prognosis of CRC.

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