Dataset Information

Clinical Significance of Potential Unidentified HLA-G Isoforms Without ?1 Domain but Containing Intron 4 in Colorectal Cancer Patients.

ABSTRACT: The ectopic HLA-G expression in malignancies has been extensively explored and clinical significance of the molecule was widely acknowledged. Besides previously well-documented seven isoforms (HLA-G1~-G7), other novel isoforms of HLA-G have been reported but their clinical relavenace remians evaluated. In this study, lesion HLA-G expression in 379 case-matched serial section primary colorectal cancers (CRC) were evaluated with mAb 4H84 (recognizing an epitope in HLA-G ?1 domain), and mAb 5A6G7 (recognizing an epitope encoded by intron 4), respectively. Data showed that HLA-G positive staining with mAbs 4H84 and 5A6G7 was 70.7 and 60.4%, respectively. When percentage of HLA-G expression detected with mAb 4H84 subtracted that with mAb 5A6G7, the difference (?HLA-G) with negative (?HLA-Gneg), comparable (?HLA-Gcom) and positive (?HLA-Gpos) were observed in 64 (16.9%), 159 (42.0%), and 156 (41.2%) cases, respectively. Noteworthy, unexpected immunostaining was observed in 44 (11.6%) lesions that no staining was detected with mAb 4H84 but positive with mAb 5A6G7 (4H84neg5A6G7pos). This staining pattern was unpredictable because all seven known HLA-G isoforms containing the ? 1 domain could be recognized by the mAb 4H84. Moreover, patients with ?HLA-Gneg had obviously better survival than those with ?HLA-Gcom and ?HLA-Gpos (p = 0.017), and ?HLA-G could be an independent prognostic factor for CRC patients (p = 0.008). Our findings provides the first report that potential unidentified HLA-G isoforms is of distinct clinical significance in CRC patients.

SUBMITTER: Lin A

PROVIDER: S-EPMC6131604 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Clinical Significance of Potential Unidentified HLA-G Isoforms Without α1 Domain but Containing Intron 4 in Colorectal Cancer Patients.

Lin Aifen A Zhang Xia X Zhang Rui-Li RL Zhang Jian-Gang JG Zhou Wen-Jun WJ Yan Wei-Hua WH

Frontiers in oncology 20180904

The ectopic HLA-G expression in malignancies has been extensively explored and clinical significance of the molecule was widely acknowledged. Besides previously well-documented seven isoforms (HLA-G1~-G7), other novel isoforms of HLA-G have been reported but their clinical relavenace remians evaluated. In this study, lesion HLA-G expression in 379 case-matched serial section primary colorectal cancers (CRC) were evaluated with mAb 4H84 (recognizing an epitope in HLA-G α1 domain), and mAb 5A6G7 ( ...[more]

PMID: 30234020

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Project description:BackgroundGamma-aminobutyric acid type B (GABAB) receptors decrease neural activity through G protein signaling. There are two subunits, GABAB1 and GABAB2. Alternative splicing provides GABAB1 with structural and functional diversity. cDNA microarrays showed strong signals from human brain RNA using GABAB1 intron 4 region probes. Therefore, we predicted the existence of novel splice variants.Methodology/principal findingsBased on the probe sequence analysis, we proposed two possible splice variants, GABAB1j and GABAB1k. The existence of human GABAB1j was verified by quantitative real-time PCR, and mouse GABAB1j was found from a microarray probe set based on human GABAB1j sequence. GABAB1j open reading frames (ORF) and expression patterns are not conserved across species, and they do not have any important functional domains except sushi domains. Thus, we focused on another possible splice variant, GABAB1k. After obtaining PCR evidence for GABAB1k existence from human, mouse, and rat, it was cloned from human and mouse by PCR along with three additional isoforms, GABAB1l, GABAB1m, and GABAB1n. Their expression levels by quantitative real-time PCR are relatively low in brain although they may be expressed in specific cell types. GABAB1l and GABAB1m inhibit GABAB receptor-induced G protein-activated inwardly rectifying K(+) channel (GIRK) currents at Xenopus oocyte two-electrode voltage clamp system.Conclusions/significanceThis study supports previous suggestions that intron 4 of GABAB1 gene is a frequent splicing spot across species. Like GABAB1e, GABAB1l and GABAB1m do not have transmembrane domains but have a dimerization motif. So, they also could be secreted and bind GABAB2 dominantly instead of GABAB1a. However, only GABAB1l and GABAB1m are N- and C-terminal truncated splicing variants and impair receptor function. This suggests that the intron 4 containing N-terminal truncation is necessary for the inhibitory action of the new splice variants.

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Dataset Information

Clinical Significance of Potential Unidentified HLA-G Isoforms Without ?1 Domain but Containing Intron 4 in Colorectal Cancer Patients.

Publications

Clinical Significance of Potential Unidentified HLA-G Isoforms Without α1 Domain but Containing Intron 4 in Colorectal Cancer Patients.

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