Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy.
<h4>Introduction</h4>Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy.<h4>Methods</h4>To test this hypothesis, we a...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/938176a574324bc8a0bc8d0f1e4e8aa3 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:938176a574324bc8a0bc8d0f1e4e8aa3 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:938176a574324bc8a0bc8d0f1e4e8aa32021-11-18T07:56:09ZPeripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy.1932-620310.1371/journal.pone.0057053https://doaj.org/article/938176a574324bc8a0bc8d0f1e4e8aa32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23451142/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy.<h4>Methods</h4>To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment.<h4>Results</h4>Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality.<h4>Conclusions</h4>Our results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC.Yung-Che ChenChang-Chun HsiaoKuang-Den ChenYu-Chiang HungChing-Yuan WuChien-Hao LieShih-Feng LiuMing-Tse SungChung-Jen ChenTing-Ya WangJen-Chieh ChangPetrus TangWen-Feng FangYi-Hsi WangYu-Hsiu ChungTung-Ying ChaoSum-Yee LeungMao-Chang SuChin-Chou WangMeng-Chih LinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e57053 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Yung-Che Chen Chang-Chun Hsiao Kuang-Den Chen Yu-Chiang Hung Ching-Yuan Wu Chien-Hao Lie Shih-Feng Liu Ming-Tse Sung Chung-Jen Chen Ting-Ya Wang Jen-Chieh Chang Petrus Tang Wen-Feng Fang Yi-Hsi Wang Yu-Hsiu Chung Tung-Ying Chao Sum-Yee Leung Mao-Chang Su Chin-Chou Wang Meng-Chih Lin Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy. |
| description |
<h4>Introduction</h4>Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy.<h4>Methods</h4>To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment.<h4>Results</h4>Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality.<h4>Conclusions</h4>Our results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC. |
| format |
article |
| author |
Yung-Che Chen Chang-Chun Hsiao Kuang-Den Chen Yu-Chiang Hung Ching-Yuan Wu Chien-Hao Lie Shih-Feng Liu Ming-Tse Sung Chung-Jen Chen Ting-Ya Wang Jen-Chieh Chang Petrus Tang Wen-Feng Fang Yi-Hsi Wang Yu-Hsiu Chung Tung-Ying Chao Sum-Yee Leung Mao-Chang Su Chin-Chou Wang Meng-Chih Lin |
| author_facet |
Yung-Che Chen Chang-Chun Hsiao Kuang-Den Chen Yu-Chiang Hung Ching-Yuan Wu Chien-Hao Lie Shih-Feng Liu Ming-Tse Sung Chung-Jen Chen Ting-Ya Wang Jen-Chieh Chang Petrus Tang Wen-Feng Fang Yi-Hsi Wang Yu-Hsiu Chung Tung-Ying Chao Sum-Yee Leung Mao-Chang Su Chin-Chou Wang Meng-Chih Lin |
| author_sort |
Yung-Che Chen |
| title |
Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy. |
| title_short |
Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy. |
| title_full |
Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy. |
| title_fullStr |
Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy. |
| title_full_unstemmed |
Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy. |
| title_sort |
peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/938176a574324bc8a0bc8d0f1e4e8aa3 |
| work_keys_str_mv |
AT yungchechen peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT changchunhsiao peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT kuangdenchen peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT yuchianghung peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT chingyuanwu peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT chienhaolie peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT shihfengliu peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT mingtsesung peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT chungjenchen peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT tingyawang peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT jenchiehchang peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT petrustang peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT wenfengfang peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT yihsiwang peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT yuhsiuchung peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT tungyingchao peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT sumyeeleung peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT maochangsu peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT chinchouwang peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy AT mengchihlin peripheralimmunecellgeneexpressionchangesinadvancednonsmallcelllungcancerpatientstreatedwithfirstlinecombinationchemotherapy |
| _version_ |
1718422745258131456 |