Cancer Res Treat.  2015 Oct;47(4):804-812. 10.4143/crt.2014.121.

GRP78 Protein Expression as Prognostic Values in Neoadjuvant Chemoradiotherapy and Laparoscopic Surgery for Locally Advanced Rectal Cancer

Affiliations
  • 1Department of Medical Oncology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea. shimby@catholic.ac.kr
  • 2Department of Hospital Pathology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.
  • 3Department of General Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.
  • 4Department of Radiation Oncology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.
  • 5Department of Gastroenterology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.

Abstract

PURPOSE
We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1 [teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis in locally advanced rectal cancer.
MATERIALS AND METHODS
All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m2/day) and leucovorin (20 mg/m2/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GRP78 and Cripto-1 proteins was determined by immunohistochemistry and was assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT).
RESULTS
High expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and 49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with a significantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and a significantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared with high expression of GRP78 protein. Mean recurrence-free survival according to GRP78 expression could not be estimated because the low expression group did not develop recurrence events but showed a significant correlation with time to recurrence, based on the log rank method (p=0.007). GRP78 also showed correlation with overall survival, based on the log rank method (p=0.045).
CONCLUSION
GRP78 expression is a predictive and prognostic factor for down staging, recurrence, and survival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvant CRT.

Keyword

Rectal neoplasms; Molecular chaperone GRP78; TDGF1 protein; Endoplasmic reticulum stress

MeSH Terms

Biological Markers
Chemoradiotherapy*
Endoplasmic Reticulum Stress
Fluorouracil
Humans
Immunohistochemistry
Laparoscopy*
Leucovorin
Prognosis
Rectal Neoplasms*
Recurrence
Biological Markers
Fluorouracil
Leucovorin

Figure

  • Fig. 1. These are representative tissue sections used in immunohistochemical analyses. (A) Low expression of glucose-regulated protein of molecular mass 78 (GRP78, ×400). (B) High cytoplasmic expression of GRP78 (×400). (C) Low expression of Cripto-1 (×400). (D) High cytoplasmic expression of Cripto-1 (×400).

  • Fig. 2. (A) Down staging (DS) rate according to expression of glucose-regulated protein of molecular mass 78 (GRP78) protein (low expression of GRP78 [80.0%] vs. high expression of GRP78 [52.3%], respectively; p=0.046). (B) Recurrence rate (RR) according to expression of GRP78 protein (low expression of GRP78 [0%] vs. high expression of GRP78 [37.2%], respectively; p=0.004).

  • Fig. 3. Kaplan-Meier survival curves are calculated using expression patterns of glucose-regulated protein of molecular mass 78 (GRP78) for recurrence-free survival.


Reference

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