The prognostic role of tumor associated glycoprotein 72 (TAG-72) in stage II and III colorectal adenocarcinoma

Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide. About 20–30% of initially diagnosed CRC patients present with unresectable metastatic disease. The remaining 70–80% newly diagnosed with CRC have localized disease that is amenable to curative surgical resection. However, a substantial proportion of patients (40–50%) experience disease recurrence or development of metastasis after curative resection. In light of this, following curative resection, adjuvant chemotherapy with cytotoxic agents is recommended as standard clinical practice in advanced CRC patients. Recently, the number of targeted agents used in various malignancies has increased dramatically. Currently, there are seven United States Food and Drug Administration (FDA)-approved targeted agents (bevacizumab, cetuximab, panitumumab, ramucirumab, aflibercept, regorafenib, and trifluridine/tipiracil) in metastatic CRC, with many more under development and/or in clinical trials. However, CRC remains the fourth leading cause of cancer death in the world, and uncovering of new therapeutic target is needed.

Tumor associated glycoprotein 72 (TAG-72) is a membrane-bound glycoprotein complex with the properties of a mucin that is overexpressed in many adenocarcinomas occurring in the colon, stomach, esophagus, ovary, pancreas, breast, and lung, but is not expressed in most normal tissues, except for the endometrium during the secretory phase and fetal tissue. TAG-72 is expressed in 80% of CRC, with relatively little expression in the normal mucosa. In analysis of ulcerative colitis patients, the expression of TAG-72 was associated with the duration of disease and the degree of dysplasia. The employment of anti-TAG-72 monoclonal antibodies has been studied in preclinical animal models as well as in humans for cancer detection based on their high specificity against cancer antigens in various solid cancers. Monoclonal antibodies targeting TAG-72 have been used in surgery for detection of occult tumor. In particular, the combination with CEA has increased the usefulness of TAG-72. Another monoclonal antibody targeting TAG-72, minretumomab, have been introduced as a potential therapeutic target in CRC as well as breast and lung cancers. Despite these recent advances, however, the detailed expression profile of TAG-72 and its prognostic effect in CRC are not clear yet.

In this study, we investigated TAG-72 expression in CRC using newly developed 3E8 antibody, a fully humanized antibody with the highest affinity to TAG-72, and analyzed the correlations with clinicopathological characteristics. Furthermore, we analyzed the relation between TAG-72 expression and prognosis of CRC patients.

results

Conclusion

TAG-72 was more expressed in cases of CRC of higher TNM stage, and TAG-72high was associated with shorter DFS. These findings suggest that the expression of TAG-72 in CRC could be related to tumor progression, and that TAG-72 needs to be considered as a promising therapeutic target in CRC. Therapeutic strategies targeting TAG-72 have the potential to improve the prognosis of patients with CRC. Further studies are required to identify the specific mechanisms by which TAG-72 affects the tumorigenesis and progression of CRC and to examine the clinical utility of anti-TAG-72 agents.