GRP78 Protein Expression as Prognostic Values in Neoadjuvant Chemoradiotherapy and Laparoscopic Surgery for Locally Advanced Rectal Cancer
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Purpose We investigated the relationships between biomarkers related to endoplasmic reticulumstress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1[teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis inlocally advanced rectal cancer. Materials and MethodsAll 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 29to 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 andwas assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy(CRT). ResultsHigh expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with asignificantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and asignificantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared withhigh expression of GRP78 protein. Mean recurrence-free survival according to GRP78expression could not be estimated because the low expression group did not developrecurrence events but showed a significant correlation with time to recurrence, based onthe log rank method (p=0.007). GRP78 also showed correlation with overall survival, basedon the log rank method (p=0.045). ConclusionGRP78 expression is a predictive and prognostic factor for down staging, recurrence, andsurvival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvantCRT.
Abstract
Purpose We investigated the relationships between biomarkers related to endoplasmic reticulumstress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1[teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis inlocally advanced rectal cancer. Materials and MethodsAll 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 29to 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 andwas assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy(CRT). ResultsHigh expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with asignificantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and asignificantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared withhigh expression of GRP78 protein. Mean recurrence-free survival according to GRP78expression could not be estimated because the low expression group did not developrecurrence events but showed a significant correlation with time to recurrence, based onthe log rank method (p=0.007). GRP78 also showed correlation with overall survival, basedon the log rank method (p=0.045). ConclusionGRP78 expression is a predictive and prognostic factor for down staging, recurrence, andsurvival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvantCRT.
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