In this study, GC patients with higher level of KK-LC-1 expression are found to have a better prognosis, and the overall expression of KK-LC-1 protein in gastric cancer tissue was obviously higher than that in normal tissues. Fukuyama et al.[29] also found similar results: KK-LC-1 gene expression was found to be higher in tumor regions than in nontumor regions, and sometimes KK-LC-1 was found to be expressed in non-tumor sites that carrying tumors stomach tissue. In our experimental findings, KK-LC-1’s protein expression rate in tumor tissues was 95.7%. By contrast, Akiko et al. also found KK-LC-1’s gene expression rate can reach a percentage of 81.6%, which is significantly higher than others. [18] One study found that KK-LC-1’s expression rate in triple negative breast cancer was 75%.[20] These findings are similar to ours, which suggests that KK-LC-1 is likely to be highly expressed in tumors. However, no existing studies focus on the expression of tumor-associated antigens in gastric cancer as high as KK-LC-1, suggesting that KK-LC-1 can be treated as an ideal therapeutic target. For clinical diagnostic applications, high expression of tumor-associated antigens in the early stages of cancer is often considered a useful target. At present, there are few reports about the expression of the KK-LC-1 gene and protein and tumor prognosis. Thus, more research results are needed for verification.
Generally, this study’s findings suggest that there is a significant negative correlation between KK-LC-1’s protein expression and pathological grade. The higher the pathological grade is, the lower the KK-LC-1’s protein expression in the tissue and the poorer the prognosis. In contrast, the lower the pathological grade is, the higher the KK-LC-1’s protein expression in the tissue and the better the prognosis of the patient. This result also indirectly shows the reliability of our experimental data. We hypothesized that KK-LC-1 protein can be associated with the early state of the tumor and thus related to a good prognosis. Therefore, KK-LC-1 can be used as a positive biomarker directly related to prognosis, which is able to provide clinicians with more choices. For example, patients with higher KK-LC-1’s protein expression levels may obtain better results from adjuvant chemotherapy or radiotherapy than patients with lower expression levels. However, studies have also shown that the expression level of KK-LC-1 in hepatocellular carcinoma (HCC) is increased. High KK-LC-1 expression levels are associated with poor survival outcomes. At the same time, the study found that KK-LC-1 promotes cell growth, invasion, migration and epithelial-mesenchymal transition in vivo and in vitro. [30]. In summary, the abnormal KK-LC-1’s protein expression is obviously related to the occurrence and development of tumors. Therefore, KK-LC-1 may play different roles in different malignant tumors, and researchers still need to conduct more in-depth research in order to verify the true relationship between KK-LC-1 and cancer and their involvement Specific mechanism.
To date, some mechanisms concerning KK-LC-1 and neoplasia have been revealed in several tumors. According to reports, the activation of CT genes in some types of cancer is related to hypomethylation of CpG islands. CT45 is one of the 6 member families of the X-linked CT gene, and the expression of CT45 associated with hypomethylation of promoter DNA is increased in epithelial ovarian cancer. The researchers believe that CT45 expression may be a prognostic biomarker. [31]. In lung adenocarcinoma, PIWIL1 is considered to be a highly expressed CT gene. Hypomethylation of the promoter DNA of PIWIL1 can cause overexpression of CT genes [32]. However, So far, there are few reports on the function and mechanism of KK-LC-1 in human malignant tumors.
It is worth noting that our research findings can be regarded as a theoretical basis for immunotherapy and targeted therapy of different tumors involving KK-LC-1. It is suggested, based on the Human Protein Atlas database (http://www.proteinatlas.org), CT83 transcripts are expressed in various tumor cell lines, including gastric cancer, colorectal cancer, breast cancer, urothelial cancer, lung cancer, and cervical cancer. Therefore, CT83 may be a potential target for antibody-photosensitizer conjugate-based photodynamic therapy (PDT) in various malignant tumors. Ziyu Ye et al [33] developed a novel mouse anti-human CT83 monoclonal antibody (CT83 mAb 7G4), which can form an antibody-photosensitizer complex of 7g4-1-ga and can specifically recognize human CT83. In vitro experiments show that 7G4-1-Ga is more cytotoxic to CT83-expressing human cancer cells than 1-Ga. Therefore, anti-CT83 mAb may become an effective treatment for CT83-expressing tumor targeting PDT in the future.
However, the research process of our study has some potential limitations. This is a relatively single study with relatively few sample cases and few statistical analysis tools. Finally, some patients received postoperative chemotherapy or radiotherapy. Although the survival period was limited, the results did not consider these adjuvant therapies’ impact on prognosis. Therefore, multi-angle studies and further researches are needed to explore KK-LC-1’s expression in GC and we need to evaluate its clinical efficiency in a wider range of patients.