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CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas

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Abstract

CD44 and CD44 variant isoforms have been reported as contributing factors to cancer progression. In this study, we aimed to assess whether CD44 and its variant isoforms were correlated with the prognostic factors for distant metastasis in stage I lung adenocarcinomas using tissue microarray and immunohistochemistry. In this single-center retrospective study, we analyzed the data of 490 patients with stage I lung adenocarcinoma resected between 1999 and 2016. We constructed tissue microarrays and performed immunohistochemistry for CD44s, CD44v6, and CD44v9. The risk of disease recurrence and its associations with clinicopathological risk factors were assessed. CD44v6 expression was significantly associated with recurrence. Patients with CD44v6-negative tumors had a significantly increased risk of developing distant recurrence than patients with CD44v6-positive tumors (5-year cumulative incidence of recurrence (CIR), 10.7% vs. 4.6%; P = 0.009). However, CD44v6-negative tumors were not associated with an increased risk of locoregional recurrence compared to CD44v6-positive tumors (5-year CIR, 6.0% vs. 4.0%; P = 0.39). The overall survival (OS) of patients with CD44v6-negative tumors was significantly lower than that of patients with CD44v6-positive tumors (5-year OS: 87% vs. 94%, P = 0.016). CD44v6-negative tumors were also associated with invasive tumor size and lymphovascular invasion. Even in stage I disease, tumors with negative-CD44v6 expression had more distant recurrences than those with positive-CD44v6 expression and were associated with poor prognosis in resected stage I lung adenocarcinomas. Thus, CD44v6 downregulation may be a prognostic factor for distant metastasis in stage I lung adenocarcinomas.

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We confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

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Funding

This work was supported, in part, by JSPS KAKENHI (G. No. JP20K07392).

Author information

Authors and Affiliations

  1. Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Chihiro Yoshida, Kaede Yamada, Syusuke Fujimoto & Toshiki Yajima

  2. Department of General Thoracic Surgery, Kochi Health Sciences Center, Kochi, Japan

    Chihiro Yoshida

  3. Department of Pathology, Faculty of Medicine, Shimane University, Shimane, Japan

    Kyuichi Kadota

  4. Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Emi Ibuki, Ryou Ishikawa & Reiji Haba

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  1. Chihiro Yoshida
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Contributions

All authors contributed to the study conception and design. C.Y. was involved in conceptualization, formal analysis, investigation, visualization, writing—original draft preparation, and editing. K.K. helped in funding acquisition, methodology, and writing—reviewing. K.Y. contributed to data curation. S.F. was involved in data curation. E.I. and R.I. helped in resources. R.H. contributed to project administration. T.Y. helped in supervision.

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Correspondence to Kyuichi Kadota.

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The authors have no relevant financial or non-financial interests to disclose.

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This study was approved by the Institutional Review Board of Kagawa University in Japan.

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The requirement for informed consent was waived owing to the retrospective nature of the study.

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Yoshida, C., Kadota, K., Yamada, K. et al. CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas. Clin Exp Med 23, 5191–5200 (2023). https://doi.org/10.1007/s10238-023-01185-z

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