Low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer

Bo Yang, Lin Cao, Jiaen Liu, Yanjie Xu, Gillian Milne, Wanhei Chan, Steven D Heys, Colin D McCaig, Jin Pu

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Abstract

BACKGROUND: Chloride channel accessory 1 (CLCA1) is a CLCA protein that plays a functional role in regulating the differentiation and proliferation of colorectal cancer (CRC) cells. Here we investigated the relationship between the level of CLCA1 and the prognosis of CRC.

METHODS: First, the level of CLCA1 was detected quantitatively in normal and cancerous colonic epithelial tissues with immunohistochemistry. Next, the correlations between CLCA1 expression, pathological tumor features, and the overall survival rate of patients was analyzed. Finally, 3 publicly available data sets from the Gene Expression Omnibus were examined: normal CRC versus early CRC (GSE4107), primary CRC versus metastatic lesions (GSE28702), and low chromosomal instability versus high chromosomal instability (GSE30540).

RESULTS: The expression of CLCA1 was decreased markedly in tumor specimens. CLCA1 expression was correlated significantly with the histological grade (P < .01) and lymph node metastasis (P < .01). A significantly poorer overall survival rate was found in patients with low levels of CLCA1 expression versus those with high expression levels (P < .05). The results confirmed that the low expression of CLCA1 in CRC was highly associated with tumorigenesis, metastasis, and high chromosomal instability. In addition, the loss of CLCA1 disrupted the differentiation of human colon adenocarcinoma cells (Caco-2) in vitro.

CONCLUSIONS: These findings suggest that CLCA1 levels may be a potential predictor of prognosis in primary human CRC. Low expression of CLCA1 predicts disease recurrence and lower survival, and this has implications for the selection of patients most likely to need and benefit from adjuvant chemotherapy. Cancer 2015. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Original languageEnglish
Pages (from-to)1570-1580
Number of pages11
JournalCancer
Volume121
Issue number10
Early online date20 Jan 2015
DOIs
Publication statusPublished - 15 May 2015

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Chloride Channels
Colorectal Neoplasms
Chromosomal Instability
Neoplasms
Survival Rate
Neoplasm Metastasis
Caco-2 Cells
Adjuvant Chemotherapy
Patient Selection
Colon
Carcinogenesis
Adenocarcinoma
Epithelium
Lymph Nodes
Immunohistochemistry

Keywords

  • chloride channel accessory 1 (CLCA1) expression
  • colorectal carcinoma
  • prognosis
  • cell differentiation

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Low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer. / Yang, Bo; Cao, Lin; Liu, Jiaen; Xu, Yanjie; Milne, Gillian; Chan, Wanhei; Heys, Steven D; McCaig, Colin D; Pu, Jin.

In: Cancer, Vol. 121, No. 10, 15.05.2015, p. 1570-1580.

Research output: Contribution to journalArticle

Yang, B, Cao, L, Liu, J, Xu, Y, Milne, G, Chan, W, Heys, SD, McCaig, CD & Pu, J 2015, 'Low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer', Cancer, vol. 121, no. 10, pp. 1570-1580. https://doi.org/10.1002/cncr.29235
Yang, Bo ; Cao, Lin ; Liu, Jiaen ; Xu, Yanjie ; Milne, Gillian ; Chan, Wanhei ; Heys, Steven D ; McCaig, Colin D ; Pu, Jin. / Low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer. In: Cancer. 2015 ; Vol. 121, No. 10. pp. 1570-1580.
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abstract = "BACKGROUND: Chloride channel accessory 1 (CLCA1) is a CLCA protein that plays a functional role in regulating the differentiation and proliferation of colorectal cancer (CRC) cells. Here we investigated the relationship between the level of CLCA1 and the prognosis of CRC.METHODS: First, the level of CLCA1 was detected quantitatively in normal and cancerous colonic epithelial tissues with immunohistochemistry. Next, the correlations between CLCA1 expression, pathological tumor features, and the overall survival rate of patients was analyzed. Finally, 3 publicly available data sets from the Gene Expression Omnibus were examined: normal CRC versus early CRC (GSE4107), primary CRC versus metastatic lesions (GSE28702), and low chromosomal instability versus high chromosomal instability (GSE30540).RESULTS: The expression of CLCA1 was decreased markedly in tumor specimens. CLCA1 expression was correlated significantly with the histological grade (P < .01) and lymph node metastasis (P < .01). A significantly poorer overall survival rate was found in patients with low levels of CLCA1 expression versus those with high expression levels (P < .05). The results confirmed that the low expression of CLCA1 in CRC was highly associated with tumorigenesis, metastasis, and high chromosomal instability. In addition, the loss of CLCA1 disrupted the differentiation of human colon adenocarcinoma cells (Caco-2) in vitro.CONCLUSIONS: These findings suggest that CLCA1 levels may be a potential predictor of prognosis in primary human CRC. Low expression of CLCA1 predicts disease recurrence and lower survival, and this has implications for the selection of patients most likely to need and benefit from adjuvant chemotherapy. Cancer 2015. {\circledC} 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.",
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T1 - Low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer

AU - Yang, Bo

AU - Cao, Lin

AU - Liu, Jiaen

AU - Xu, Yanjie

AU - Milne, Gillian

AU - Chan, Wanhei

AU - Heys, Steven D

AU - McCaig, Colin D

AU - Pu, Jin

N1 - © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Funded by Friends of ANCHOR NHS Grampian Endowment Fund. Grant Number: 12/50

PY - 2015/5/15

Y1 - 2015/5/15

N2 - BACKGROUND: Chloride channel accessory 1 (CLCA1) is a CLCA protein that plays a functional role in regulating the differentiation and proliferation of colorectal cancer (CRC) cells. Here we investigated the relationship between the level of CLCA1 and the prognosis of CRC.METHODS: First, the level of CLCA1 was detected quantitatively in normal and cancerous colonic epithelial tissues with immunohistochemistry. Next, the correlations between CLCA1 expression, pathological tumor features, and the overall survival rate of patients was analyzed. Finally, 3 publicly available data sets from the Gene Expression Omnibus were examined: normal CRC versus early CRC (GSE4107), primary CRC versus metastatic lesions (GSE28702), and low chromosomal instability versus high chromosomal instability (GSE30540).RESULTS: The expression of CLCA1 was decreased markedly in tumor specimens. CLCA1 expression was correlated significantly with the histological grade (P < .01) and lymph node metastasis (P < .01). A significantly poorer overall survival rate was found in patients with low levels of CLCA1 expression versus those with high expression levels (P < .05). The results confirmed that the low expression of CLCA1 in CRC was highly associated with tumorigenesis, metastasis, and high chromosomal instability. In addition, the loss of CLCA1 disrupted the differentiation of human colon adenocarcinoma cells (Caco-2) in vitro.CONCLUSIONS: These findings suggest that CLCA1 levels may be a potential predictor of prognosis in primary human CRC. Low expression of CLCA1 predicts disease recurrence and lower survival, and this has implications for the selection of patients most likely to need and benefit from adjuvant chemotherapy. Cancer 2015. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

AB - BACKGROUND: Chloride channel accessory 1 (CLCA1) is a CLCA protein that plays a functional role in regulating the differentiation and proliferation of colorectal cancer (CRC) cells. Here we investigated the relationship between the level of CLCA1 and the prognosis of CRC.METHODS: First, the level of CLCA1 was detected quantitatively in normal and cancerous colonic epithelial tissues with immunohistochemistry. Next, the correlations between CLCA1 expression, pathological tumor features, and the overall survival rate of patients was analyzed. Finally, 3 publicly available data sets from the Gene Expression Omnibus were examined: normal CRC versus early CRC (GSE4107), primary CRC versus metastatic lesions (GSE28702), and low chromosomal instability versus high chromosomal instability (GSE30540).RESULTS: The expression of CLCA1 was decreased markedly in tumor specimens. CLCA1 expression was correlated significantly with the histological grade (P < .01) and lymph node metastasis (P < .01). A significantly poorer overall survival rate was found in patients with low levels of CLCA1 expression versus those with high expression levels (P < .05). The results confirmed that the low expression of CLCA1 in CRC was highly associated with tumorigenesis, metastasis, and high chromosomal instability. In addition, the loss of CLCA1 disrupted the differentiation of human colon adenocarcinoma cells (Caco-2) in vitro.CONCLUSIONS: These findings suggest that CLCA1 levels may be a potential predictor of prognosis in primary human CRC. Low expression of CLCA1 predicts disease recurrence and lower survival, and this has implications for the selection of patients most likely to need and benefit from adjuvant chemotherapy. Cancer 2015. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

KW - chloride channel accessory 1 (CLCA1) expression

KW - colorectal carcinoma

KW - prognosis

KW - cell differentiation

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VL - 121

SP - 1570

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JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 10

ER -