Lack of XAGE‐1b and NY‐ESO‐1 in metastatic lymph nodes may predict the potential survival of stage III melanoma patients

Abstract

The cancer-testis antigens (CTA) are a large family of tumor-associated antigens expressed by a variety of cancer cells and primitive germ cells of the adult testis and placenta. These tumor-restricted expressing patterns suggest that CTA would be ideal targets for tumor-specific immunotherapy. XAGE-1 is a CTA that was originally identified by computer-based screening, and four transcription variants, XAGE-1a, -1b, -1c and -1d, have been characterized to date. Although the presence of XAGE-1 transcripts has been reported in various cancers, the expression of XAGE-1b in melanoma has not been fully characterized. In this study, we performed immunohistochemical staining of XAGE-1b together with NY-ESO-1, a well-known CTA, in 113 melanoma samples obtained from 84 patients and evaluated their expression in tumor cells. The effects of expression on tumor progression and patient prognosis were analyzed. Both XAGE-1b and NY-ESO-1 were expressed at high levels in lymph node metastasis and skin metastasis samples compared with the primary site (P < 0.01 in XAGE-1b and P < 0.05 in NY-ESO-1). In a subgroup analysis of 22 patients with stage III lymph node metastasis, overall survival was significantly higher in the XAGE-1b and NY-ESO-1 double-negative group than in the other groups (P < 0.05). These results suggest that lack of XAGE-1b and NY-ESO-1 expression could have a positive influence on clinical outcome in patients with melanoma.

XAGE-1b Promotes the Proliferation, Invasion and Metastasis of Gastric Cancer

“…The result of XAGE-1b is compatible with other tumor, which reported that XAGE-1b + group with melanoma showed poorer prognosis [5] . These ndings demonstrate that XAGE-1b may be related to biological events of GC.…”

“…XAGE-1b is considered as a tumor serological marker which assisted clinical diagnosis [7,14] . Moreover, signi cant dysregulated levels of XAGE-1b were observed in several tumors [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]21] . However, XAGE-1b expression in GC and its role in the prognosis of GC patients remain unclear.…”

“…XAGE-1b is characterized as wide expression spectrum, high expression rate and strong immunogenicity, which also leads to a variety of transcription variations. It has been reported that XAGE-1b was highly expressed in melanoma [5,6] , lung cancer [7][8][9][10][11][12][13] , prostate cancer [14,15] and hepatocellular carcinoma [16,17] , and was correlated with the tumor poor prognosis.…”

Tumor immune microenvironment of cutaneous angiosarcoma with cancer testis antigens and the formation of tertiary lymphoid structures

“…NY-ESO-1 and XAGE-1B are one of the CTAs, which are a large family of tumor-associated antigens only in germ cells of the testis and placenta ( 12 , 13 ), and in various malignant tumors, such as melanoma ( 14 ), squamous cell carcinoma ( 15 ), non-small cell lung cancer ( 16 ), gastric cancer ( 17 ), hepatocellular carcinoma ( 18 ), breast cancer ( 19 ), ovarian cancer ( 20 ), bladder cancer ( 21 ), prostate cancer ( 22 ), multiple myeloma ( 23 ), synovial sarcoma ( 24 ), and Ewing’s sarcoma ( 25 ). CTAs can be divided into two groups, those that are encoded on the X chromosome (CT-X antigens) and those that are not (non-X CT antigens) ( 13 ).…”

“…In patients with hepatocellular carcinoma, elevated serum XAGE-1B tends to be associated with a higher recurrence rate, and may be useful as a prognostic biomarker ( 18 ). Similarly, also in melanoma, lack of NY-ESO-1 and XAGE-1B in metastatic lymph nodes prolonged overall survival ( 14 ). CAS has been reported to be positive by immunostaining for MAGEA4 and NY-ESO-1 ( 28 ), which are CTAs, but whether or not XAGE-1 is expressed in CAS and its usefulness as a prognostic factor have not been clarified.…”