Dissertation > Medicine, health > Oncology > General issues > Tumor pathology, etiology

The Relationship between GRP78 Expression with the Cancer Occurrence and Recurrence: Meta-analysis

Author ZhouZuo
Tutor ShenGuanXin
School Huazhong University of Science and Technology
Course Immunology
Keywords GRP78 Meta analysis tumor survival rate melocular target
CLC R730.2
Type PhD thesis
Year 2011
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【Background】The cancer occurrence and progression is a complication program, revolving mulfactors. Currently, the mechanisms and the pathogeny of carnocima are not clear yet. Glucose-regulated protein of 78 kDa (GRP78), know as immunoglobulin heavy chain bingding protein (Bip), is a member of heat shock protein 70 family, located in endoplasmic reticulum (ER) and plays a crucial role. As a chaperone protein of ER, GRP78 takes part in prohibition of the accumulation of nascent proteins, obtaining intracellular Ca2+ homeostasis, antiapoptosis induced by ER stress, and initiation unfolded protein response. Recently studies have shown that the GRP78 expression is strong relative to hepatic steatosis, cancer and neurodegenerative diseases. All the studies reminded researcher should pay more attention to the biological characters of GRP78. Some studies releaved on cancer progression, the cancer cells increased expression of GRP78 was associated with the tumor cell proliferation, drug-resistance and metastasis. GRP78 can inhibit apoptosis through its known ability to bind to and inhibit caspases-7, which provide protection from Doxorubicin-induced apoptosis pathway. Associated with initiation of malignancy, poor vascularization of the tumor mass leads to poor conditions in the tumor microenvironment, such as low oxygen supply, nutrient deprivation and pH changes. These conditions induced GRP78 overexpression, which allow cancer cells to escape the apoptotic pathway. GRP78 induces the upregulation of the unfolded protein response in cancers, maybe it benefit for tumor cells by increasing the protein folding capacity and prolong cancer cells life. Observation in some cancer studies, overexpression of GRP78 in tumor tissues, we propose that GRP78 play a crucial role in cancer cells resist to drug. It could be a tumor target for cancer therapeutic. In this study, we try to use system review and Meta analysis to find out the relationship between the expressions of GRP78 with cancer progression.【Purpose】Pooling the recently studies regarding to the relationship between GRP78 and cancer progression, analysis the possibility of treat GRP78 as a signature of judgement the cancer prognosis. Piling the studies relavence of differently expression of GRP78 in tumor tissues and normal tissues or adjacent tissues, suggest GRP78 as a target melocular for cancer treatment.【Method】A systematic review was conducted following the guidelines of Cochrane Collaboration. A system research has been performed in electronic databases. Confirm to strict selection criteria in terms of types of participants, interventions types and methods to limit verification bias. Where possible we calculated the specificity, sensitivity, negative and positive predictive value of GRP78 overpression. The results were displayed using forest plots.【Results】1. We identified 8 studies fulfilling the inclusion criteria for relevant the relationship between the expression of GRP78 and cancer progression. Completed the Meta analysis, we find out the survive time of GRP78 overexpression group is dramatically shorter than those of GRP78 lower expression group. Furthermore, the reoccurrence rate of GRP78 overexpression group is apprenently higher than those of GRP78 lower expression group.2. Regarding to the possibility of using GRP78 as molecular target, there are 9 studies were selected for system review. There are totally 1470 tumor samples. We treat expression rate higher than 25% as overexpression and less than 25% as lower expression. The result is: there are 1092 cancer tissue samples overexpressed GRP78, 74.29%; while 85 samples of adjacent tissue with GRP78 overexpression, 12.94%; compared with normal tissues 30 samples highly expressed GRP78, 12.25%. The OR value is 24.93, 95% CI is 14.80 to 41.81. The area under SROC curve was 0.9289 and Q index was 0.8638. GRP78 can be regarded as molecular targets for theyapy against cancer.【Conclusion】GRP78 expression is relative to cancer progression. We could look GRP78 as prognosis symbol. Since GRP78 overexpress in tumor tissues, the result of this research gives us a hint that it would be developed as a melocular targets for therapeutic method.

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