The Expression Levels of IL-4/IL-13/STAT6 Signaling Pathway Genes and SOCS3 Could Help to Differentiate the Histopathological Subtypes of Non-Small Cell Lung Carcinoma

Background The interleukin (IL)-4/IL-13/signal transducer and activator of transcription (STAT) 6 signaling pathway and the SOCS3 gene, one of its main regulators, constitute an important link between the inflammation process in the epithelial cells and inflammatory-related tumorigenesis. The presen...

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Veröffentlicht in:Molecular diagnosis & therapy 2018-10, Vol.22 (5), p.621-629
Hauptverfasser: Pastuszak-Lewandoska, Dorota, Domańska-Senderowska, Daria, Antczak, Adam, Kordiak, Jacek, Górski, Paweł, Czarnecka, Karolina H., Migdalska-Sęk, Monika, Nawrot, Ewa, Kiszałkiewicz, Justyna M., Brzeziańska-Lasota, Ewa
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container_issue 5
container_start_page 621
container_title Molecular diagnosis & therapy
container_volume 22
creator Pastuszak-Lewandoska, Dorota
Domańska-Senderowska, Daria
Antczak, Adam
Kordiak, Jacek
Górski, Paweł
Czarnecka, Karolina H.
Migdalska-Sęk, Monika
Nawrot, Ewa
Kiszałkiewicz, Justyna M.
Brzeziańska-Lasota, Ewa
description Background The interleukin (IL)-4/IL-13/signal transducer and activator of transcription (STAT) 6 signaling pathway and the SOCS3 gene, one of its main regulators, constitute an important link between the inflammation process in the epithelial cells and inflammatory-related tumorigenesis. The present study is the first to evaluate IL-4, IL-13, STAT6 , and SOCS3 mRNA expression in non-small cell lung carcinoma (NSCLC) histopathological subtypes. Methods Gene expression levels were assessed using TaqMan ® probes by quantitative reverse transcription PCR (qRT-PCR) in lung tumor samples and unchanged lung tissue samples. Results Increased expression of IL-4 , IL-13 , and STAT6 was observed in all histopathological NSCLC subtypes (squamous cell carcinoma [SCC], adenocarcinoma [AC], and large cell carcinoma [LCC]). Significantly higher expression of IL-13 and STAT6 ( p  = 0.019 and p  = 0.008, respectively) was found in SCC than in LCC. No statistically significant differences were found for IL-4 . Significantly higher SOCS3 expression was found in LCC than in AC ( p  = 0.027). A negative correlation (rho = –0.519) was observed for the STAT6 and SOCS3 genes in SCC ( p  = 0.005). No associations were found between gene expression and tumor staging (post-operative Tumor Node Metastasis [pTNM], American Joint Committee on Cancer [AJCC]), patients’ age, sex, or history of smoking. Conclusions As the number of LCC cases in our study was quite low, the statistically significant results obtained should be confirmed in a larger group of patients, particularly as the relationships identified between increased IL-4, IL-13, and STAT6 mRNA expression and decreased SOCS3 expression suggest that these genes may serve as potential diagnostic markers for differentiating between NSCLC histopathological subtypes.
doi_str_mv 10.1007/s40291-018-0355-7
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The present study is the first to evaluate IL-4, IL-13, STAT6 , and SOCS3 mRNA expression in non-small cell lung carcinoma (NSCLC) histopathological subtypes. Methods Gene expression levels were assessed using TaqMan ® probes by quantitative reverse transcription PCR (qRT-PCR) in lung tumor samples and unchanged lung tissue samples. Results Increased expression of IL-4 , IL-13 , and STAT6 was observed in all histopathological NSCLC subtypes (squamous cell carcinoma [SCC], adenocarcinoma [AC], and large cell carcinoma [LCC]). Significantly higher expression of IL-13 and STAT6 ( p  = 0.019 and p  = 0.008, respectively) was found in SCC than in LCC. No statistically significant differences were found for IL-4 . Significantly higher SOCS3 expression was found in LCC than in AC ( p  = 0.027). A negative correlation (rho = –0.519) was observed for the STAT6 and SOCS3 genes in SCC ( p  = 0.005). No associations were found between gene expression and tumor staging (post-operative Tumor Node Metastasis [pTNM], American Joint Committee on Cancer [AJCC]), patients’ age, sex, or history of smoking. Conclusions As the number of LCC cases in our study was quite low, the statistically significant results obtained should be confirmed in a larger group of patients, particularly as the relationships identified between increased IL-4, IL-13, and STAT6 mRNA expression and decreased SOCS3 expression suggest that these genes may serve as potential diagnostic markers for differentiating between NSCLC histopathological subtypes.</description><identifier>ISSN: 1177-1062</identifier><identifier>EISSN: 1179-2000</identifier><identifier>DOI: 10.1007/s40291-018-0355-7</identifier><identifier>PMID: 30105735</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adenocarcinoma ; Aged ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; Breast cancer ; Cancer Research ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - pathology ; Cell Line, Tumor ; Cytokines ; Diagnostic systems ; Epithelial cells ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genes ; Growth factors ; Human Genetics ; Humans ; Inflammation ; Inflammatory diseases ; Interleukin 13 ; Interleukin 4 ; Interleukin-13 - genetics ; Interleukin-4 - genetics ; Kinases ; Laboratory Medicine ; Lung cancer ; Lung carcinoma ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Male ; Metastases ; Middle Aged ; Molecular Medicine ; Neoplasm Grading ; Neoplasm Staging ; Non-small cell lung carcinoma ; Original ; Original Research Article ; Patients ; Pharmacotherapy ; Prostate cancer ; Proteins ; Regulators ; Reverse transcription ; Samples ; Signal Transduction ; Signaling ; Small cell lung carcinoma ; Smoking ; Squamous cell carcinoma ; Stat6 protein ; STAT6 Transcription Factor - metabolism ; Statistical analysis ; Statistical methods ; Statistical significance ; Studies ; Suppressor of Cytokine Signaling 3 Protein - genetics ; Thoracic surgery ; Tumorigenesis ; Tumors</subject><ispartof>Molecular diagnosis &amp; therapy, 2018-10, Vol.22 (5), p.621-629</ispartof><rights>The Author(s) 2018</rights><rights>Copyright Springer Nature B.V. 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The present study is the first to evaluate IL-4, IL-13, STAT6 , and SOCS3 mRNA expression in non-small cell lung carcinoma (NSCLC) histopathological subtypes. Methods Gene expression levels were assessed using TaqMan ® probes by quantitative reverse transcription PCR (qRT-PCR) in lung tumor samples and unchanged lung tissue samples. Results Increased expression of IL-4 , IL-13 , and STAT6 was observed in all histopathological NSCLC subtypes (squamous cell carcinoma [SCC], adenocarcinoma [AC], and large cell carcinoma [LCC]). Significantly higher expression of IL-13 and STAT6 ( p  = 0.019 and p  = 0.008, respectively) was found in SCC than in LCC. No statistically significant differences were found for IL-4 . Significantly higher SOCS3 expression was found in LCC than in AC ( p  = 0.027). A negative correlation (rho = –0.519) was observed for the STAT6 and SOCS3 genes in SCC ( p  = 0.005). No associations were found between gene expression and tumor staging (post-operative Tumor Node Metastasis [pTNM], American Joint Committee on Cancer [AJCC]), patients’ age, sex, or history of smoking. Conclusions As the number of LCC cases in our study was quite low, the statistically significant results obtained should be confirmed in a larger group of patients, particularly as the relationships identified between increased IL-4, IL-13, and STAT6 mRNA expression and decreased SOCS3 expression suggest that these genes may serve as potential diagnostic markers for differentiating between NSCLC histopathological subtypes.</description><subject>Adenocarcinoma</subject><subject>Aged</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Breast cancer</subject><subject>Cancer Research</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cytokines</subject><subject>Diagnostic systems</subject><subject>Epithelial cells</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Growth factors</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammatory diseases</subject><subject>Interleukin 13</subject><subject>Interleukin 4</subject><subject>Interleukin-13 - genetics</subject><subject>Interleukin-4 - genetics</subject><subject>Kinases</subject><subject>Laboratory Medicine</subject><subject>Lung cancer</subject><subject>Lung carcinoma</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Staging</subject><subject>Non-small cell lung carcinoma</subject><subject>Original</subject><subject>Original Research Article</subject><subject>Patients</subject><subject>Pharmacotherapy</subject><subject>Prostate cancer</subject><subject>Proteins</subject><subject>Regulators</subject><subject>Reverse transcription</subject><subject>Samples</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Small cell lung carcinoma</subject><subject>Smoking</subject><subject>Squamous cell carcinoma</subject><subject>Stat6 protein</subject><subject>STAT6 Transcription Factor - metabolism</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Statistical significance</subject><subject>Studies</subject><subject>Suppressor of Cytokine Signaling 3 Protein - genetics</subject><subject>Thoracic surgery</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>1177-1062</issn><issn>1179-2000</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1UUtv1DAQjhCIlsIP4IIscQ47fuR1QarS0q0UUaQsZ8txJruuvHGwk8L-Iv4mbrcUOHCZGWm-x2i-JHlL4QMFKFZBAKtoCrRMgWdZWjxLTiktqpQBwPOHuUgp5OwkeRXCLYDI8oq9TE44UMgKnp0mPzc7JJc_Jo8hGDeSBu_QBuIGct2kYhUL5at2c77JSWu2o7Jm3JIvat59VwdyhSMGosaetDd1y0ntFtuTNdqJzI5cmGFAj-Ns1Ixkjj5rE2Y3RbKzbmu0sqRduvkw4YPhZzem7V5ZS2qMpVmiU628NqPbq9fJi0HZgG8e-1ny9dPlpl6nzc3VdX3epFoUMKd9x5TWVSkwVzlSBh2USveC5oIXKLohK7uqGpDpoct4X9GO9fnQQ6lL1au-42fJx6PutHR77HU83ysrJ2_2yh-kU0b-uxnNTm7dncwpZ0JAFHj_KODdtwXDLG_d4uPjgmS04lAJJmhE0SNKexeCx-HJgYK8z1Yes5UxW3mfrSwi593fpz0xfocZAewICHE1btH_sf6_6i-pZ7D7</recordid><startdate>20181001</startdate><enddate>20181001</enddate><creator>Pastuszak-Lewandoska, Dorota</creator><creator>Domańska-Senderowska, Daria</creator><creator>Antczak, Adam</creator><creator>Kordiak, Jacek</creator><creator>Górski, Paweł</creator><creator>Czarnecka, Karolina H.</creator><creator>Migdalska-Sęk, Monika</creator><creator>Nawrot, Ewa</creator><creator>Kiszałkiewicz, Justyna M.</creator><creator>Brzeziańska-Lasota, Ewa</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>4T-</scope><scope>7QO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7602-9203</orcidid></search><sort><creationdate>20181001</creationdate><title>The Expression Levels of IL-4/IL-13/STAT6 Signaling Pathway Genes and SOCS3 Could Help to Differentiate the Histopathological Subtypes of Non-Small Cell Lung Carcinoma</title><author>Pastuszak-Lewandoska, Dorota ; Domańska-Senderowska, Daria ; Antczak, Adam ; Kordiak, Jacek ; Górski, Paweł ; Czarnecka, Karolina H. ; Migdalska-Sęk, Monika ; Nawrot, Ewa ; Kiszałkiewicz, Justyna M. ; Brzeziańska-Lasota, Ewa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-db2acc984e6a6e120b08acd416437e4bf58b99fe2cfb53d91b2d6fd08c8adadb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adenocarcinoma</topic><topic>Aged</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Breast cancer</topic><topic>Cancer Research</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cytokines</topic><topic>Diagnostic systems</topic><topic>Epithelial cells</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Growth factors</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammatory diseases</topic><topic>Interleukin 13</topic><topic>Interleukin 4</topic><topic>Interleukin-13 - genetics</topic><topic>Interleukin-4 - genetics</topic><topic>Kinases</topic><topic>Laboratory Medicine</topic><topic>Lung cancer</topic><topic>Lung carcinoma</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Staging</topic><topic>Non-small cell lung carcinoma</topic><topic>Original</topic><topic>Original Research Article</topic><topic>Patients</topic><topic>Pharmacotherapy</topic><topic>Prostate cancer</topic><topic>Proteins</topic><topic>Regulators</topic><topic>Reverse transcription</topic><topic>Samples</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Small cell lung carcinoma</topic><topic>Smoking</topic><topic>Squamous cell carcinoma</topic><topic>Stat6 protein</topic><topic>STAT6 Transcription Factor - 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The present study is the first to evaluate IL-4, IL-13, STAT6 , and SOCS3 mRNA expression in non-small cell lung carcinoma (NSCLC) histopathological subtypes. Methods Gene expression levels were assessed using TaqMan ® probes by quantitative reverse transcription PCR (qRT-PCR) in lung tumor samples and unchanged lung tissue samples. Results Increased expression of IL-4 , IL-13 , and STAT6 was observed in all histopathological NSCLC subtypes (squamous cell carcinoma [SCC], adenocarcinoma [AC], and large cell carcinoma [LCC]). Significantly higher expression of IL-13 and STAT6 ( p  = 0.019 and p  = 0.008, respectively) was found in SCC than in LCC. No statistically significant differences were found for IL-4 . Significantly higher SOCS3 expression was found in LCC than in AC ( p  = 0.027). A negative correlation (rho = –0.519) was observed for the STAT6 and SOCS3 genes in SCC ( p  = 0.005). No associations were found between gene expression and tumor staging (post-operative Tumor Node Metastasis [pTNM], American Joint Committee on Cancer [AJCC]), patients’ age, sex, or history of smoking. Conclusions As the number of LCC cases in our study was quite low, the statistically significant results obtained should be confirmed in a larger group of patients, particularly as the relationships identified between increased IL-4, IL-13, and STAT6 mRNA expression and decreased SOCS3 expression suggest that these genes may serve as potential diagnostic markers for differentiating between NSCLC histopathological subtypes.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>30105735</pmid><doi>10.1007/s40291-018-0355-7</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-7602-9203</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adenocarcinoma
Aged
Apoptosis
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - pathology
Cell Line, Tumor
Cytokines
Diagnostic systems
Epithelial cells
Female
Gene expression
Gene Expression Regulation, Neoplastic
Genes
Growth factors
Human Genetics
Humans
Inflammation
Inflammatory diseases
Interleukin 13
Interleukin 4
Interleukin-13 - genetics
Interleukin-4 - genetics
Kinases
Laboratory Medicine
Lung cancer
Lung carcinoma
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Male
Metastases
Middle Aged
Molecular Medicine
Neoplasm Grading
Neoplasm Staging
Non-small cell lung carcinoma
Original
Original Research Article
Patients
Pharmacotherapy
Prostate cancer
Proteins
Regulators
Reverse transcription
Samples
Signal Transduction
Signaling
Small cell lung carcinoma
Smoking
Squamous cell carcinoma
Stat6 protein
STAT6 Transcription Factor - metabolism
Statistical analysis
Statistical methods
Statistical significance
Studies
Suppressor of Cytokine Signaling 3 Protein - genetics
Thoracic surgery
Tumorigenesis
Tumors
title The Expression Levels of IL-4/IL-13/STAT6 Signaling Pathway Genes and SOCS3 Could Help to Differentiate the Histopathological Subtypes of Non-Small Cell Lung Carcinoma
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