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

• Published in: Cancer research and treatment Vol. 47; no. 4; pp. 804 - 812
• Main Authors: Lee, Hee Yeon, Jung, Ji-Han, Cho, Hyun-Min, Kim, Sung Hwan, Lee, Kang-Moon, Kim, Hyung-Jin, Lee, Jong Hoon, Shim, Byoung Yong
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01.10.2015; 대한암학회
• Subjects: Aged; Biomarkers, Tumor; Chemoradiotherapy, Adjuvant - methods; Female; Fluorouracil - administration & dosage; Fluorouracil - therapeutic use; GPI-Linked Proteins - genetics; GPI-Linked Proteins - metabolism; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Humans; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Laparoscopy; Leucovorin - administration & dosage; Leucovorin - therapeutic use; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Original; Prognosis; Rectal Neoplasms - metabolism; Rectal Neoplasms - therapy; 의약학; TDGF1 protein; Molecular chaperone GRP78; Rectal neoplasms; Endoplasmic reticulum stress
• ISSN: 1598-2998; 2005-9256; 2005-9256
• DOI: 10.4143/crt.2014.121

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. All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m(2)/day) and leucovorin (20 mg/m(2)/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). 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). 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.