[GRP78 expression in gastric cancer and its clinical significance].
OBJECTIVE
To investigate the clinical value of the expression of glucose regulated protein 78 (GRP78) for assessment of severity, chemoresistance and prognosis in patients with gastric adenocarcinoma ( GC) .


METHODS
A cohort of 237 patients with gastric cancer was included in this study. 160 patients of them were treated by D2 radical gastrectomy and adjuvant chemotherapy. The GRP78 expression was detected by immunohistochemistry and 80 patients of them were tested in vitro for cancer chemosensitivity by ATP-tumor chemosensitivity assay (ATP-TCA). In addition, the relationships were analyzed between GRP78 and age, gender, tumor differentiation, invasion, disease stage, lymph node metastasis and chemoresistance as well as disease-free survival (DFS).


RESULTS
The positive rate of GRP78 expression in the gastric adenocarcinoma was 68.8% before the initiation of chemotherapy. The positive GRP78 expression was significantly correlated with tumor invasion depth, poor differentiation, TNM stages, and lymph node metastasis (all P < 0.05), not correlated with gender and age, and high GRP78 expression was associated with the chemoresistance of the gastric cancer cells to chemotherapeutic agents. Negative GRP78 expression was associated with higher sensitivity to both drugs and regimens. The DFS of GRP78-positive group and GRP78-negative group was (53.6 ± 0.9) months and (38.3 ± 0.8) months, respectively (P = 0.041). Interestingly, subgroup analysis revealed that the DFS in GRP78-negative and-positive patients treated with taxane-containing chemotherapy was (58.6 ± 2.6) months and (49.1 ± 2.7) months, respectively, but the difference was statistically not significant (P = 0.111). In contrast, in the subset of GRP78-negative and- positive patients treated with taxane-containing regimens, the DFS was (45.5 ± 1.9) months and (35.1 ± 2.2) months, respectively, showing a significant difference (P = 0.038). In the group of patients with positive GRP78 expression, the patients treated with taxane-containing chemotherapy had a longer DFS [(49.1 ± 2.7) months] than those without that treatment [(35.1 ± 2.2) months], showing a significant difference (P = 0.017). Univariate analysis revealed that DFS was correlated with histological grade, GRP78 expression and lymph node metastasis (all P < 0.05). Multivariate analysis showed that GRP78 expression and TNM staging were independent influencing factors for gastric cancer (both P < 0.05).


CONCLUSIONS
The results of our study suggest that GRP78 may be a novel biomarker for assessment of malignant degree and prediction of chemoresistance in gastric cancer, and may be helpful to chemotherapy planning and prognosis prediction in patients with gastric cancer.
Department of Medical Oncology, Nantong University Tumor Hospital, Nantong 226361, China.
Lei
L
Yang
Department of Medical Oncology, Nantong University Tumor Hospital, Nantong 226361, China.
Shu-yun
SY
Yang
Department of Medical Oncology, Nantong University Tumor Hospital, Nantong 226361, China.
Jian-mei
JM
Ji
Department of Medical Oncology, Nantong University Tumor Hospital, Nantong 226361, China.
Yong-feng
YF
Cao
Department of Medical Oncology, Nantong University Tumor Hospital, Nantong 226361, China.
Cong-fei
CF
Ji
Department of Medical Oncology, Nantong University Tumor Hospital, Nantong 226361, China.
Jin-feng
JF
Ji
Department of Medical Oncology, Nantong University Tumor Hospital, Nantong 226361, China.
Wei-wei
WW
Xu
Department of Medical Oncology, Nantong University Tumor Hospital, Nantong 226361, China. Email: leiyang.53@163.com.
Jian-hong
JH
Wang
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005743:Gastrectomy; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D043823:Taxoids / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D043823:Taxoids; C080625:taxane