Common Variants in Osteopontin and <i>CD44</i> Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer
Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single n...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/23/2721 |
| _version_ | 1797400342636265472 |
|---|---|
| author | Seweryn Gałecki Agnieszka Gdowicz-Kłosok Regina Deja Barbara Masłyk Monika Giglok Rafał Suwiński Dorota Butkiewicz |
| author_facet | Seweryn Gałecki Agnieszka Gdowicz-Kłosok Regina Deja Barbara Masłyk Monika Giglok Rafał Suwiński Dorota Butkiewicz |
| author_sort | Seweryn Gałecki |
| collection | DOAJ |
| description | Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the <i>OPN</i> and <i>CD44</i> genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also investigated. Multivariate analysis showed that <i>OPN</i> rs11730582 CC carriers had a significantly increased risk of death (<i>p</i> = 0.029), while the <i>CD44</i> rs187116 A allele correlated with a reduced risk of locoregional recurrence (<i>p</i> = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (<i>p</i> = 0.016). Furthermore, the <i>OPN</i> rs1126772 G variant alone (<i>p</i> = 0.018) and in combination with rs11730582 CC (<i>p</i> = 7 × 10<sup>−5</sup>) was associated with poor overall survival (OS) in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG, and rs1126772 G, as well as their respective combinations, were independent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that <i>OPN</i> and <i>CD44</i> germline variants may predict treatment effects in NSCLC. |
| first_indexed | 2024-03-09T01:54:09Z |
| format | Article |
| id | doaj.art-b88961d69604437cb4549192dba89df9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T01:54:09Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b88961d69604437cb4549192dba89df92023-12-08T15:13:09ZengMDPI AGCells2073-44092023-11-011223272110.3390/cells12232721Common Variants in Osteopontin and <i>CD44</i> Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung CancerSeweryn Gałecki0Agnieszka Gdowicz-Kłosok1Regina Deja2Barbara Masłyk3Monika Giglok4Rafał Suwiński5Dorota Butkiewicz6Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, PolandCenter for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, PolandAnalytics and Clinical Biochemistry Department, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, PolandAnalytics and Clinical Biochemistry Department, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, PolandII Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, PolandII Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, PolandCenter for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, PolandOsteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the <i>OPN</i> and <i>CD44</i> genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also investigated. Multivariate analysis showed that <i>OPN</i> rs11730582 CC carriers had a significantly increased risk of death (<i>p</i> = 0.029), while the <i>CD44</i> rs187116 A allele correlated with a reduced risk of locoregional recurrence (<i>p</i> = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (<i>p</i> = 0.016). Furthermore, the <i>OPN</i> rs1126772 G variant alone (<i>p</i> = 0.018) and in combination with rs11730582 CC (<i>p</i> = 7 × 10<sup>−5</sup>) was associated with poor overall survival (OS) in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG, and rs1126772 G, as well as their respective combinations, were independent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that <i>OPN</i> and <i>CD44</i> germline variants may predict treatment effects in NSCLC.https://www.mdpi.com/2073-4409/12/23/2721osteopontinOPNSPP1CD44lung cancerpolymorphism |
| spellingShingle | Seweryn Gałecki Agnieszka Gdowicz-Kłosok Regina Deja Barbara Masłyk Monika Giglok Rafał Suwiński Dorota Butkiewicz Common Variants in Osteopontin and <i>CD44</i> Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer Cells osteopontin OPN SPP1 CD44 lung cancer polymorphism |
| title | Common Variants in Osteopontin and <i>CD44</i> Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer |
| title_full | Common Variants in Osteopontin and <i>CD44</i> Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer |
| title_fullStr | Common Variants in Osteopontin and <i>CD44</i> Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer |
| title_full_unstemmed | Common Variants in Osteopontin and <i>CD44</i> Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer |
| title_short | Common Variants in Osteopontin and <i>CD44</i> Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer |
| title_sort | common variants in osteopontin and i cd44 i genes as predictors of treatment outcome in radiotherapy and chemoradiotherapy for non small cell lung cancer |
| topic | osteopontin OPN SPP1 CD44 lung cancer polymorphism |
| url | https://www.mdpi.com/2073-4409/12/23/2721 |
| work_keys_str_mv | AT seweryngałecki commonvariantsinosteopontinandicd44igenesaspredictorsoftreatmentoutcomeinradiotherapyandchemoradiotherapyfornonsmallcelllungcancer AT agnieszkagdowiczkłosok commonvariantsinosteopontinandicd44igenesaspredictorsoftreatmentoutcomeinradiotherapyandchemoradiotherapyfornonsmallcelllungcancer AT reginadeja commonvariantsinosteopontinandicd44igenesaspredictorsoftreatmentoutcomeinradiotherapyandchemoradiotherapyfornonsmallcelllungcancer AT barbaramasłyk commonvariantsinosteopontinandicd44igenesaspredictorsoftreatmentoutcomeinradiotherapyandchemoradiotherapyfornonsmallcelllungcancer AT monikagiglok commonvariantsinosteopontinandicd44igenesaspredictorsoftreatmentoutcomeinradiotherapyandchemoradiotherapyfornonsmallcelllungcancer AT rafałsuwinski commonvariantsinosteopontinandicd44igenesaspredictorsoftreatmentoutcomeinradiotherapyandchemoradiotherapyfornonsmallcelllungcancer AT dorotabutkiewicz commonvariantsinosteopontinandicd44igenesaspredictorsoftreatmentoutcomeinradiotherapyandchemoradiotherapyfornonsmallcelllungcancer |