PDCD4 as a Predictor of Sensitivity to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients

Abstract

Objective: The purpose of this study was to examine the role of programmed cell death 4 (PDCD4) expression in predicting tumor response to neoadjuvant chemoradiotherapy and outcomes for patients with locally advanced rectal cancer. Methods: Clinicopathological factors and expression of PDCD4 were evaluated in 92 patients with LARC treated with nCRT. After the completion of therapy, 4 cases achieved clinical complete response (cCR), and thus the remaining 88 patients underwent a standardized total mesorectal excision procedure. There were 38 patients (41.3%) with a good response (TRG 3-4) and 54 (58.7%) with a poor one (TRG 0-2). Results: Immunohistochemical staining analyses showed that patients with high expression of PDCD4 were more sensitive to nCRT than those with low PDCD4 expression (P=0.02). High PDCD4 expression before nCRT and good response (TRG3-4) were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis demonstrated that the pretreatment PDCD4 expression was an independent prognostic factor. Conclusion: Our study demonstrated that high expression of PDCD4 protein is a useful predictive factor for good tumor response to nCRT and good outcomes in patients with LARC.

The clinical association of programmed cell death protein 4 (PDCD4) with solid tumors and its prognostic significance: a meta-analysis

“…In most of the studies included in prognostic assessment, all clinical stages were represented in the respective cancer cases. However, the study reported by Dou et al [32], only focused on advanced stage rectal cancer, and the low PDCD4 expression within these patients was not significantly associated with the 5-year OS or DFS indicated by the 95% CI overlapping 1. Furthermore, the subcellular localization of the PDCD4 protein affects cancer behavior.…”

“…Combined analysis of the 20 studies in 10 papers that addressed OS [7, 15, 17, 18, 24, 28–32] showed that reduced PDCD4 expression had an unfavorable impact on the OS of patients with solid tumors (HR: 2.24, 95% CI 1.93–2.60) (Table 3). Significant associations were observed in the univariate model (HR: 2.05, 95% CI 1.69–2.49) and multivariate model (HR: 2.52, 95% CI 2.01–3.16) (Fig.…”

“…4a). Subgroup analysis of different tumor types (Table 3) showed that reduced PDCD4 expression had an unfavorable impact on the OS of patients with head and neck cancers (HR: 3.24, 95% CI 1.93–5.45) [18, 24, 29], breast cancers (HR: 1.86, 95% CI 1.36–2.54) [30], digestive system cancers (HR: 2.12, 95% CI 1.75–2.56) [7, 15, 28, 31, 32], and urinary system cancers (HR: 3.16, 95% CI 1.06–9.41) [17]. No evidence of significant publication bias was observed with Begg’s test ( P  = 0.940) and Egger’s test ( P  = 0.744) (Fig.…”

“…6a) [29–32, 35]. Low PDCD4 expression was associated with short DFS/RFS of patients with head and neck cancers (HR: 2.10, 95% CI 1.30–3.39) [29], digestive system cancers (HR: 2.57, 95% CI 1.74–3.78) [31, 32], and gynecologic cancers (HR: 3.42, 95% CI 1.41–8.33) [35]; for breast cancer patients, no association was observed (HR: 1.23, 95% CI 0.79–1.92) [30] (Table 3). The Begg’s test ( P  = 0.902) and Egger’s test ( P  = 0.550) showed no significant publication bias (Fig.…”

Network Mapping of Molecular Biomarkers Influencing Radiation Response in Rectal Cancer

“…Programmed cell death Apoptotic index, 12,29 Bax, 14,16,30 BIRC5, [10][11][12][13] caspase-8, 31 hPEBP4, 32,33 M30, 34 MIB1, 15 p53, [14][15][16][17][18][19] PDCD4, 35 phospho-Akt, 21 XIAP, 36 YKL-40 27…”