RAD51 is a poor prognostic marker and a potential therapeutic target for oral squamous cell carcinoma

Yu-Fen Tsai; Leong-Perng Chan; Yuk-Kwan Chen; Chang-Wei Su; Ching-Wei Hsu; Yen-Yun Wang; Shyng-Shiou F Yuan

doi:10.1186/s12935-023-03071-w

RAD51 is a poor prognostic marker and a potential therapeutic target for oral squamous cell carcinoma

Cancer Cell Int. 2023 Oct 5;23(1):231. doi: 10.1186/s12935-023-03071-w.

Authors

Yu-Fen Tsai^{1

2

3}, Leong-Perng Chan^{4

5

6}, Yuk-Kwan Chen^{7

8}, Chang-Wei Su^{7

9}, Ching-Wei Hsu^{7

8}, Yen-Yun Wang^{10

11

12}, Shyng-Shiou F Yuan^{13

14

15

16

17

18}

Affiliations

¹ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
² Department of Hematology and Oncology, E-Da Cancer Hospital, I-Shou University, Kaohsiung, 824, Taiwan.
³ School of Chinese Medicine for Post Baccalaureate, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan.
⁴ Cohort Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
⁵ Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
⁶ Department of Otorhinolaryngology-Head and Neck Surgery, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan.
⁷ School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
⁸ Division of Oral Pathology & Maxillofacial Radiology, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan.
⁹ Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
¹⁰ School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. wyy@kmu.edu.tw.
¹¹ Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. wyy@kmu.edu.tw.
¹² Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan. wyy@kmu.edu.tw.
¹³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. yuanssf@kmu.edu.tw.
¹⁴ Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. yuanssf@kmu.edu.tw.
¹⁵ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan. yuanssf@kmu.edu.tw.
¹⁶ Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, 75 Bo-Ai Street, Hsinchu, 300, Taiwan. yuanssf@kmu.edu.tw.
¹⁷ Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan. yuanssf@kmu.edu.tw.
¹⁸ Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan. yuanssf@kmu.edu.tw.

Abstract

Objectives: RAD51 overexpression has been reported to serve as a marker of poor prognosis in several cancer types. This study aimed to survey the role of RAD51 in oral squamous cell carcinoma and whether RAD51 could be a potential therapeutic target.

Materials and methods: RAD51 protein expression, assessed by immunohistochemical staining, was used to examine associations with survival and clinicopathological profiles of patients with oral squamous cell carcinoma. Lentiviral infection was used to knock down or overexpress RAD51. The influence of RAD51 on the biological profile of oral cancer cells was evaluated. Cell viability and apoptosis after treatment with chemotherapeutic agents and irradiation were analyzed. Co-treatment with chemotherapeutic agents and B02, a RAD51 inhibitor, was used to examine additional cytotoxic effects.

Results: Oral squamous cell carcinoma patients with higher RAD51 expression exhibited worse survival, especially those treated with adjuvant chemotherapy and radiotherapy. RAD51 overexpression promotes resistance to chemotherapy and radiotherapy in oral cancer cells in vitro. Higher tumorsphere formation ability was observed in RAD51 overexpressing oral cancer cells. However, the expression of oral cancer stem cell markers did not change in immunoblotting analysis. Co-treatment with RAD51 inhibitor B02 and cisplatin, compared with cisplatin alone, significantly enhanced cytotoxicity in oral cancer cells.

Conclusion: RAD51 is a poor prognostic marker for oral squamous cell carcinoma. High RAD51 protein expression associates with resistance to chemotherapy and radiotherapy. Addition of B02 significantly increased the cytotoxicity of cisplatin. These findings suggest that RAD51 protein may function as a treatment target for oral cancer.

Trial registration: Number: KMUHIRB-E(I)-20190009 Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, approved on 20190130, Retrospective registration.

Keywords: B02; Chemotherapy and radiotherapy resistance; Oral squamous cell carcinoma; RAD51.

Abstract

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