Colorectal cancer (CRC) is one of the most common malignancy globally (1). Approximately 63,500 new cases are reported annually in Indonesia and most of them is located in rectal region (2). Clinical and pathological features of CRC are different according to tumor location, along with it’s molecular marker profile (3). Glucose-related Protein 94 (GRP94)  is one of biomarkers in CRC. It plays role in formation and proliferation of cancer stem cells through influencing ETV1 and COX2 expression. This contributes to therapeutic resistance, metastatic spread, and relapse of CRC (4). This study aims to evaluate the expression of GRP94 which may aid in better management, diagnosis, and prognostic scoring of CRC patients.

This study found high expression of GRP94 in subjects with distal CRC. (p=0.019). Significant difference of GRP94 expression was found between distal and rectal CRC (p=0.007). Expression of GRP94 was associated with CRC location. This result demonstrated that stemness level is higher at certain location and may subsequently daughter cells with higher heterogeneity. Previous study reported an absence of difference in the expression of GRP94 based on CRC location, but confirmed that GRP94 expression is associated with primary tumor size, grade of histological differentiation, and patient’s survival (5). There are other studies on liver and breast cancer. GRP94 inhibition has been shown to reduce proliferation and growth of hepatocellular carcinoma via CCT8/c-Jun/EMT signaling pathway (6). Silencing GRP94 in a mouse xenograft model led to suppression of AKT signaling and reduced liver tumor development (7). In breast cancer, pharmacological blockade of GRP94 resulted in HER2 destabilization and inhibited RAF1-MAPK survival pathways (8). GRP94 depletion decreased the proliferation and motility of aggressive MDA-MB-231 breast cancer cells (9).  Previous study reported that patients with rectal CRC had the highest median survival (10). This is in contrast with our result. We found that GRP94 expression is significantly higher in distal CRC, which associated with poor prognosis. It suggests that GRP94 may possess tumor suppressing property. Other studies proposed that GRP94 can stimulate antitumor immune responses by enhancing MHC class I molecule-mediated antigen presentation and promoting maturation and activation of immune cells. However, this condition occurs when tumor stress or damage surpasses a certain thresholds (11, 12).

As the conclusion, there is a statistically significant association between GRP94 expression and location of CRC. Higher expression is observed in distal CRC, raising awareness towards patients with this feature particularly regarding disease outcome.

To read the full research article, please visit the link below:
Association Between Glucose-related Protein 94 (GRP94) and Colorectal Cancer Location – PubMed

Authors:
1. Imelda Rey, MD, Ph.D
2. Rustam Effendi YS, MD, Ph.D

Affiliation:
Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan
Columbia Asia Hospital, Medan

Image Source:
iStcock (credit: ChrisChrisW)

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