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. 2017 Nov 30;9(12):163.
doi: 10.3390/cancers9120163.

Early Postoperative Low Expression of RAD50 in Rectal Cancer Patients Associates with Disease-Free Survival

Vincent Ho  1 , Liping Chung  2   3 , Amandeep Singh  4 , Vivienne Lea  5 , Maxine Revoltar  6 , Stephanie H Lim  7   8   9 , Thein-Ga Tut  10 , Weng Ng  11 , Mark Lee  12 , Paul de Souza  13   14   15 , Joo-Shik Shin  16 , Cheok Soon Lee  17   18   19   20
Affiliations

Early Postoperative Low Expression of RAD50 in Rectal Cancer Patients Associates with Disease-Free Survival

Vincent Ho et al. Cancers (Basel). .

Abstract

Background: Molecular biomarkers have the potential to predict response to the treatment of rectal cancer. In this study, we aimed to evaluate the prognostic and clinicopathological implication of RAD50 (DNA repair protein RAD50 homolog) expression in rectal cancer.

Methods: A total of 266 rectal cancer patients who underwent surgery and received chemo- and radiotherapy between 2000 and 2011 were involved in the study. Postoperative RAD50 expression was determined by immunohistochemistry in surgical samples (n = 266).

Results: Using Kaplan-Meier survival analysis, we found that low RAD50 expression in postoperative samples was associated with worse disease free survival (p = 0.001) and overall survival (p < 0.001) in early stage/low-grade tumors. In a comparison of patients with low vs. high RAD50 expression, we found that low levels of postoperative RAD50 expression in rectal cancer tissues were significantly associated with perineural invasion (p = 0.002).

Conclusion: Expression of RAD50 in rectal cancer may serve as a prognostic biomarker for long-term survival of patients with perineural invasion-positive tumors and for potential use in early stage and low-grade rectal cancer assessment.

Keywords: DNA damage response; RAD50; biomarkers; prognosis; rectal cancer.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Association between postoperative RAD50 (DNA repair protein RAD50 homolog) expression in the TC (tumor core) and TP (tumor periphery) and survival. (A–D) Kaplan–Meier survival analysis illustrating DFS (disease free survival) (A,C) and OS (overall survival) (B,D) of patients with RAD50 expression in the TC (A,B) and TP (C,D). Blue lines represent patients with low RAD50 expression and green lines represent patients with high RAD50 expression.
Figure 2
Figure 2
Correlation between RAD50 expression and perineural invasion (PNI) and survival in early stage rectal cancers. (A,B) Representative immunohistochemical staining of RAD50 in rectal cancer samples (high versus low expression), images were taken at 10× magnification; (C,D) Kaplan–Meier survival analysis of DFS in low RAD50 expression (C) and high RAD50 expression (D) groups with (green line) or without (blue line) perineural invasion; (E,F) Kaplan–Meier survival analysis illustrating the relationship of RAD50 expression with DFS (E) and OS (F) in low-grade (G1–2) with early tumor stage (T1–2) subgroup. The analyses were divided into four subgroups including the low-grade with early stage tumors (G1–2, T1–2, n = 64), high-grade with early stage tumors (G3, T1–2, n = 4), low-grade with late stage tumors (G1–2, T3–4, n = 113), and high-grade with late stage tumors (G3, T3–4, n = 8).
Figure 2
Figure 2
Correlation between RAD50 expression and perineural invasion (PNI) and survival in early stage rectal cancers. (A,B) Representative immunohistochemical staining of RAD50 in rectal cancer samples (high versus low expression), images were taken at 10× magnification; (C,D) Kaplan–Meier survival analysis of DFS in low RAD50 expression (C) and high RAD50 expression (D) groups with (green line) or without (blue line) perineural invasion; (E,F) Kaplan–Meier survival analysis illustrating the relationship of RAD50 expression with DFS (E) and OS (F) in low-grade (G1–2) with early tumor stage (T1–2) subgroup. The analyses were divided into four subgroups including the low-grade with early stage tumors (G1–2, T1–2, n = 64), high-grade with early stage tumors (G3, T1–2, n = 4), low-grade with late stage tumors (G1–2, T3–4, n = 113), and high-grade with late stage tumors (G3, T3–4, n = 8).
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