Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer

IL-10 is associated with tumor malignancy via immune escape. We hypothesized that IL-10 haplotypes categorized by IL-10 promoter polymorphisms at –1082A>G, –819C>T, and –592C>A might influence IL-10 expression and give rise to non-small cell lung cancer (NSCLC) patients with poor outcomes a...

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Main Authors:	Wang, Yaw-Cheng, Sung, Wen-Wei, Wu, Tzu-Chin, Wang, Lee, Chien, Wen-Pin, Cheng, Ya-Wen, Chen, Chih-Yi, Shieh, Shwn-Huey, Lee, Huei
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407146/

id	pubmed-3407146
recordtype	oai_dc
spelling	pubmed-34071462012-07-30 Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer Wang, Yaw-Cheng Sung, Wen-Wei Wu, Tzu-Chin Wang, Lee Chien, Wen-Pin Cheng, Ya-Wen Chen, Chih-Yi Shieh, Shwn-Huey Lee, Huei Research Article IL-10 is associated with tumor malignancy via immune escape. We hypothesized that IL-10 haplotypes categorized by IL-10 promoter polymorphisms at –1082A>G, –819C>T, and –592C>A might influence IL-10 expression and give rise to non-small cell lung cancer (NSCLC) patients with poor outcomes and relapse. We collected adjacent normal tissues from 385 NSCLC patients to determine IL-10 haplotypes by direct sequencing and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Of the 385 tumors, 241 were available to evaluate IL-10 mRNA expression levels by real-time RT-PCR. The influence of IL-10 haplotypes on overall survival (OS) and relapse free survival (RFS) were determined by Kaplan-Meier and multivariate Cox regression analysis. The results showed that IL-10 mRNA levels were significantly higher in tumors with the non-ATA haplotype than with the ATA haplotype (P = 0.004). Patients with the non-ATA haplotype had shorter OS and RFS periods than did patients with the ATA haplotype. This may be associated with the observation that the number of tumor-infiltrating lymphocytes was decreased in the tumors with higher levels of IL-10. Consistently, T cells from the peripheral blood of the patients with non-ATA haplotype were more susceptible to apoptosis and less cytotoxic to tumor cells, compared to those from the patients with ATA haplotype. The results suggest that IL-10 can promote tumor malignancy via promoting T cell apoptosis and tumor cell survival, and IL-10 haplotype evaluated by PCR-RFLP or direct sequencing may be used to predict survival and relapse in resected NSCLC, helping clinicians to make appropriate decisions on treatment of the patients. Public Library of Science 2012-07-27 /pmc/articles/PMC3407146/ /pubmed/22848356 http://dx.doi.org/10.1371/journal.pone.0039525 Text en © 2012 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, Yaw-Cheng Sung, Wen-Wei Wu, Tzu-Chin Wang, Lee Chien, Wen-Pin Cheng, Ya-Wen Chen, Chih-Yi Shieh, Shwn-Huey Lee, Huei
spellingShingle	Wang, Yaw-Cheng Sung, Wen-Wei Wu, Tzu-Chin Wang, Lee Chien, Wen-Pin Cheng, Ya-Wen Chen, Chih-Yi Shieh, Shwn-Huey Lee, Huei Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer
author_facet	Wang, Yaw-Cheng Sung, Wen-Wei Wu, Tzu-Chin Wang, Lee Chien, Wen-Pin Cheng, Ya-Wen Chen, Chih-Yi Shieh, Shwn-Huey Lee, Huei
author_sort	Wang, Yaw-Cheng
title	Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer
title_short	Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer
title_full	Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer
title_fullStr	Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer
title_full_unstemmed	Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer
title_sort	interleukin-10 haplotype may predict survival and relapse in resected non-small cell lung cancer
description	IL-10 is associated with tumor malignancy via immune escape. We hypothesized that IL-10 haplotypes categorized by IL-10 promoter polymorphisms at –1082A>G, –819C>T, and –592C>A might influence IL-10 expression and give rise to non-small cell lung cancer (NSCLC) patients with poor outcomes and relapse. We collected adjacent normal tissues from 385 NSCLC patients to determine IL-10 haplotypes by direct sequencing and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Of the 385 tumors, 241 were available to evaluate IL-10 mRNA expression levels by real-time RT-PCR. The influence of IL-10 haplotypes on overall survival (OS) and relapse free survival (RFS) were determined by Kaplan-Meier and multivariate Cox regression analysis. The results showed that IL-10 mRNA levels were significantly higher in tumors with the non-ATA haplotype than with the ATA haplotype (P = 0.004). Patients with the non-ATA haplotype had shorter OS and RFS periods than did patients with the ATA haplotype. This may be associated with the observation that the number of tumor-infiltrating lymphocytes was decreased in the tumors with higher levels of IL-10. Consistently, T cells from the peripheral blood of the patients with non-ATA haplotype were more susceptible to apoptosis and less cytotoxic to tumor cells, compared to those from the patients with ATA haplotype. The results suggest that IL-10 can promote tumor malignancy via promoting T cell apoptosis and tumor cell survival, and IL-10 haplotype evaluated by PCR-RFLP or direct sequencing may be used to predict survival and relapse in resected NSCLC, helping clinicians to make appropriate decisions on treatment of the patients.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407146/
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Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer

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