Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Common Variants in Osteopontin and CD44 Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer

Seweryn Gałecki
ORCID logo ,
Agnieszka Gdowicz-Kłosok
,
Regina Deja
,
Barbara Masłyk
,
Monika Giglok
,
Rafał Suwiński
,
Dorota Butkiewicz
*
Version 1 : Received: 13 November 2023 / Approved: 13 November 2023 / Online: 13 November 2023 (13:06:01 CET)

A peer-reviewed article of this Preprint also exists.

Gałecki, S.; Gdowicz-Kłosok, A.; Deja, R.; Masłyk, B.; Giglok, M.; Suwiński, R.; Butkiewicz, D. Common Variants in Osteopontin and CD44 Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer. Cells 2023, 12, 2721. Gałecki, S.; Gdowicz-Kłosok, A.; Deja, R.; Masłyk, B.; Giglok, M.; Suwiński, R.; Butkiewicz, D. Common Variants in Osteopontin and CD44 Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer. Cells 2023, 12, 2721.

Abstract

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 OPN and CD44 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 inves-tigated. Multivariate analysis showed that OPN rs11730582 CC carriers had a significantly in-creased risk of death (p = 0.029), while the CD44 rs187116 A allele correlated with reduced risk of locoregional recurrence (p = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (p = 0.016). Fur-thermore, the OPN rs1126772 G variant alone (p = 0.018) and in combination with rs11730582 CC (p = 7x10-5) was associated with poor OS in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG and rs1126772 G, as well as their respective combinations, were in-dependent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that OPN and CD44 germline variants may predict treatment effects in NSCLC.

Keywords

osteopontin; OPN; SPP1; CD44; lung cancer; polymorphism; cancer progression; metastasis; prognosis; radiotherapy; curative treatment

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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