Clinical significance of golgi protein‐73 as a diagnostic marker for Egyptian patients with colorectal cancer: Preliminary study

Abstract Background Colorectal cancer is one of the most common cancers and the leading cause of cancer‐related death worldwide. Early diagnostic methods help in therapeutic success and higher survival rate. Golgi protein 73 (gp73) could help in diagnosis of colorectal cancer at an earlier stage. Aim A case‐control study aimed to assess serum level of golgi protein 73 (gp73) as a liquid biopsy marker in Egyptian colorectal cancer patients. Methods and results In the current study, ninty (90) patients were included and classified into three groups; thirty (30) patients with Colorectal cancer (CRC) as study group; 30 patients (20 patients with irritable bowel disease and 10 patients with rectal polyps) as pathological control and 30 healthy adult individuals as normal control. The diagnosis was based on the history, clinical, laboratory, endoscopic, and histological data. Golgiprotein 73 (GP73) was measured by ELISA immunoassay Kit. Serum GP73 level was higher in CRC patients than pathological control group and normal control group with high sensitivity and specificity p < .005. Conclusion GP73 alone or combined with Carcinoembryonic antigen (CEA) may be good diagnositic marker in CRC. However large studies are warranted on different stages of the disease to assess its diagnostic and prognositic value.


| INTRODUCTION
Colorectal cancer (CRC) is characterized by accumulation of environmental factors, genetic mutations, and epigenetic changes in the colonic epithelium that eventually results in neoplastic transformation. 1 Various screening and diagnostic methods for CRC are available, the methods range from invasive and costly procedures such as colonoscopy to cheap and noninvasive tests such as the fecal occult blood test. 2 While colonoscopy and sigmoidoscopy are the most sensitive procedures for diagnostic examinations, these procedures are difficult to implement on a population-wide basis due to many disadvantages including cost, invasiveness, a higher risk of perforation, and postprocedural bleeding. 3 On the other hand, the cheap and noninvasive fecal occult blood test has poor patient compliance, variations in analytical procedures such as different methods of stool collection and handling, the need for multiple test samples, and variations in the interpretation of test. 4 Golgi protein 73 (GP73) is a 73-kD transmembrane glycoprotein that located in the cis-Golgi complex. 5 It is also known as Golgi membrane protein 1 (GOLM1) or Golgi phosphoprotein 2 is expressed Golgi has been shown to play an active role in cell migration through posttranslational modification and prominent changes in the Golgi apparatus, as evidenced by the disruption of biochemical composition, structure, and functional levels observed in human carcinogenesis and metastasis. 7 Gp73 is also expressed colon cancer, a finding that may have diagnostic value. 8 So, it is important to assess the role of GP73 as a diagnostic tumor marker in patients with CRC.   F I G U R E 3 Receiver operating characteristic curve studying the validity of gp73, CEA, and combined marker of GP73 and CEA as diagnostic biomarkers for CRC

| DISCUSSION
Some factors interfere with the early diagnosis of CRC as most patients have no or nonspecific symptoms in the early stages CRC in addition to the presence of some defects in early diagnosis, determination of prognostic factors and metastatic disease treatment despite the great progress in the screening and management programs. So is mandatory to find a noninvasive, sensitive, specific, and cost-effective test that helps the early diagnosis of CRC. 9 Blood-based CRC biomarkers should be easy to perform, not risky to the patient, can be repeated at shorter intervals, identify the high risk population therefore allowing early detection and reducing CRC incidence rate. 10 Due to the heterogeneous nature of CRC, it difficult to find a single sensitive and specific screening biomarker for CRC. Instead, multiple markers may be combined to early detect CRC. 1  diagnostic performance was better than CEA. On the contrary, in absence of liver metastases, the performance of CEA was comparable to gp73. At the cut-off level of 15 ng/ml, GP73 sensitivity of was 80% and its specificity was 100%. At the level of 5 ng/ml, the sensitivity and specificity of CEA were 72 and 100%, respectively. Accordingly, serum gp73 seems to be a useful tumor marker in CRC patients. 8 El-Zefzafy et al in 2015 did not find a correlation between GP73 levels and CEA. 18 On the opposite hand Ozal et al found the performance of CEA is similar to GP73 at the cut-off level of 15 ng/ml. 8 In the present study, there is a positive correlation between gp 73 and CEA level and gp 73 in patients with CRC by using spearman correlation coefficient test p < .05 and absence of correlation with other parameters. On the opposite hand El-Zefzafy et al did not find a correlation between GP73 levels and CEA. 17 The main limitation of this study was the small sample size, limited duration of the study, absence of patients with distant metastasis were included in the current study to explore the level of Gp73 in advanced stage of the disease.

| CONCLUSIONS
GP73 has good diagnositic performance in CRC patients; Further studies on large scale of CRC patients with different stages of the disease are warranted to elucidate its clinical value in CRC patients.

CONFLICT OF INTEREST
Authors declare there is no conflict of interest.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restriction.

ETHICS STATEMENT
Ethics was followed out in accordance with the Helsinki Declaration.
An informed written consent was obtained from each individual and approval from local ethical committee at Suez Canal University, Faculty of Medicine.