Impact of RhoA overexpression on clinical outcomes in cervical squamous cell carcinoma treated with concurrent chemoradiotherapy

Author:

Tanaka Keiichi1,Matsumoto Yoshitaka1,Ishikawa Hitoshi1,Fukumitsu Nobuyoshi2,Numajiri Haruko1,Murofushi Keiko1,Oshiro Yoshiko1,Okumura Toshiyuki1,Satoh Toyomi3,Sakurai Hideyuki1

Affiliation:

1. Proton Medical Research Center, University of Tsukuba, 2-1-1 Amakubo, Tsukuba, Ibaraki 305-8576, Japan

2. Department of Radiation Oncology, Kobe Proton Center, 1-6-8, Minatoshima-minamimachi, Chuou-ku, Kobe, 650-0047, Japan

3. Obstetrics & Gynecology of University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan

Abstract

Abstract The Rho-associated coiled-coil-containing protein kinase (ROCK) pathway is known to influence metastasis in several cancers; however, the impact of the pathway on clinical outcomes in patients undergoing radiotherapy remains unknown. In the present study, the expression of RhoA, RhoC, ROCK-1, ROCK-2 and p53 was immunohistochemically evaluated using biopsy specimens obtained from 49 patients with stage II–III cervical squamous cell carcinoma treated with concurrent chemoradiotherapy (CCRT). The relationship between the expression of these proteins and patient outcomes was investigated. RhoA overexpression was associated with significantly impaired disease-free survival and distant metastasis-free survival (P = 0.045 and P = 0.041, respectively) in stage III cancer patients. No differences in survival were observed based on the expression of the other proteins among stage III cancer patients. In stage II cancer patients, no differences in survival were noted based on the expression of any of the proteins. The expression of RhoA was able to successfully differentiate cervical cancer patients with distant metastasis after CCRT. This information may help stratify patients according to the risk of metastasis, thereby leading to the potential to provide individualized treatment.

Funder

Ministry of Education, Science and Sport

Grants-in-Aid for Scientific Research

Publisher

Oxford University Press (OUP)

Subject

Health, Toxicology and Mutagenesis,Radiology Nuclear Medicine and imaging,Radiation

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