Serum Sialyl-Tn Antigen Level as a Prognostic Indicator in Patients With Gastric-Cancer

Maeda, Kiyoshi; Chung, Yong‐Suk; Onoda, N; Nakanishi, I; Nitta, Akihiro; Arimoto, Yuki; Yamada, Noriko; Kondo, Yukifumi; Kato, Yasuo; Sowa, Michio

doi:10.3892/ijo.4.1.129

Cited by 3 publications

(3 citation statements)

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“…Unsurprisingly, a high level of serum STn was significantly associated with tumor size, lymph node, liver metastasis and advanced stages in gastric cancers [ 72 , 73 , 76 ]. Furthermore, high serum STn was found to be associated with a decreased overall survival of patients with gastric [ 72 , 88 , 89 ], colorectal [ 83 , 90 ] or ovarian [ 86 , 87 ] cancers. Thus, STn detection in serum is more useful for prognosis than for diagnosis and is usually considered as a poor prognosis marker.…”

Section: Stn Immunodetection In Tissues and Tumorsmentioning

confidence: 99%

“…In gastric cancers, numerous studies reported a positive association of STn expression (in serum or primary tumors) with lymph node metastasis [ 25 , 73 , 75 , 88 , 89 , 93 ], peritoneal metastasis [ 25 , 73 , 77 , 88 ] and liver metastasis [ 73 , 88 ] with few contradicting reports [ 65 ]. Logically, many authors also reported a correlation between STn expression and decreased survival [ 26 , 65 , 72 , 75 , 88 , 94 ].…”

Section: Stn Immunodetection In Tissues and Tumorsmentioning

confidence: 99%

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Sialyl-Tn in Cancer: (How) Did We Miss the Target?

2012

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Sialyl-Tn antigen (STn) is a short O-glycan containing a sialic acid residue α2,6-linked to GalNAcα-O-Ser/Thr. The biosynthesis of STn is mediated by a specific sialyltransferase termed ST6GalNAc I, which competes with O-glycans elongating glycosyltransferases and prevents cancer cells from exhibiting longer O-glycans. While weakly expressed by fetal and normal adult tissues, STn is expressed by more than 80% of human carcinomas and in all cases, STn detection is associated with adverse outcome and decreased overall survival for the patients. Because of its pan-carcinoma expression associated with an adverse outcome, an anti-cancer vaccine, named Theratope, has been designed towards the STn epitope. In spite of the great enthusiasm around this immunotherapy, Theratope failed on Phase III clinical trial. However, in lieu of missing this target, one should consider to revise the Theratope design and the actual facts. In this review, we highlight the many lessons that can be learned from this failure from the immunological standpoint, as well as from the drug design and formulation and patient selection. Moreover, an irrefutable knowledge is arising from novel immunotherapies targeting other carbohydrate antigens and STn carrier proteins, such as MUC1, that will warrantee the future development of more successful anti-STn immunotherapy strategies.

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Section: Stn Immunodetection In Tissues and Tumorsmentioning

confidence: 99%

Section: Stn Immunodetection In Tissues and Tumorsmentioning

confidence: 99%

Sialyl-Tn in Cancer: (How) Did We Miss the Target?

2012

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“…Gastric cancer-associated antigens on the cytoplasmic membrane are known to include carcinoembryonic antigen (CEA) [33], Lewis antigens such as CA19-9 [4] and mucin antigens such as sialylTn antigen [29]. In immunohistochemical studies, CEA was expressed in 31.7-56.8% of gastric carcinomas [34][35][36], CA19-9 in 45.9-62.0% [34,37,38], and sialyl-Tn antigen in 48.7% [39]; these rates are also not high.…”

Section: Discussionmentioning

confidence: 99%

F1α: A Novel Mucin Antigen Associated with Gastric Carcinogenesis

et al. 1997

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In a previous study, we obtained a novel monoclonal antibody (F1α-75) directed against a synthetic mucin antigen termed F1α, and demonstrated that this antigen was expressed in a high percentage (80.2%; 89/111) of gastric carcinomas. In the present study, we compared the expression of F1α with that of sialyl-Tn antigen, a mucin antigen similar to F1α, in 54 human early gastric carcinomas, intestinal metaplasia and adenomatous polyps of the stomach to determine how differences in the expression of these antigens correlated with gastric carcinogenesis. The rate of expression of F1α in early gastric carcinoma tissues, 81.5%, was higher than that of sialyl-Tn antigen, 57.4%. No correlation was found between the rate of expression and histological type, depth of cancerous invasion or lymph node metastasis. Sialyl-Tn antigen was extensively expressed in 77.5% of specimens of complete intestinal metaplasia and in 78.6% of those of incomplete intestinal metaplasia; however, the expression of F1α in those specimens was rare and sporadic, with rates of only 25.0 and 27.7%, respectively. In adenomatous polyps, the rate of expression of F1α is 6.25% and that of sialyl-Tn antigen is 43.8%. Our findings indicate that F1α is a more specific antigen for gastric cancer than sialyl-Tn antigen, and that F1α is an antigen associated with carcinogenesis of the stomach.

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Truncated O-Glycan-Bearing MUC16 Enhances Pancreatic Cancer Cells Aggressiveness via α4β1 Integrin Complexes and FAK Signaling

Rajesh

Sagar

Rathinavel

et al. 2022

IJMS

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Elevated levels of Mucin-16 (MUC16) in conjunction with a high expression of truncated O-glycans is implicated in playing crucial roles in the malignancy of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms by which such aberrant glycoforms present on MUC16 itself promote an increased disease burden in PDAC are yet to be elucidated. This study demonstrates that the CRISPR/Cas9-mediated genetic deletion of MUC16 in PDAC cells decreases tumor cell migration. We found that MUC16 enhances tumor malignancy by activating the integrin-linked kinase and focal adhesion kinase (ILK/FAK)-signaling axis. These findings are especially noteworthy in truncated O-glycan (Tn and STn antigen)-expressing PDAC cells. Activation of these oncogenic-signaling pathways resulted in part from interactions between MUC16 and integrin complexes (α4β1), which showed a stronger association with aberrant glycoforms of MUC16. Using a monoclonal antibody to functionally hinder MUC16 significantly reduced the migratory cascades in our model. Together, these findings suggest that truncated O-glycan containing MUC16 exacerbates malignancy in PDAC by activating FAK signaling through specific interactions with α4 and β1 integrin complexes on cancer cell membranes. Targeting these aberrant glycoforms of MUC16 can aid in the development of a novel platform to study and treat metastatic pancreatic cancer.

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Serum Sialyl-Tn Antigen Level as a Prognostic Indicator in Patients With Gastric-Cancer

Cited by 3 publications

References 0 publications

Sialyl-Tn in Cancer: (How) Did We Miss the Target?

Sialyl-Tn in Cancer: (How) Did We Miss the Target?

F1α: A Novel Mucin Antigen Associated with Gastric Carcinogenesis

Truncated O-Glycan-Bearing MUC16 Enhances Pancreatic Cancer Cells Aggressiveness via α4β1 Integrin Complexes and FAK Signaling

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