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BMC Cancer. 2018 May 2;18(1):494. doi: 10.1186/s12885-018-4429-z.

LYL1 gene amplification predicts poor survival of patients with uterine corpus endometrial carcinoma: analysis of the Cancer genome atlas data.

Author information

1
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Daehak-Ro, Jongno-Gu, Seoul, Republic of Korea.
2
Gongwu Genomic Medicine Institute (G2MI), Medical Research Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
3
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
4
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Daehak-Ro, Jongno-Gu, Seoul, Republic of Korea. marialeemd@gmail.com.
5
Gongwu Genomic Medicine Institute (G2MI), Medical Research Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. jeongsun@snu.ac.kr.
6
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. jeongsun@snu.ac.kr.
7
Macrogen Inc., Seoul, Republic of Korea. jeongsun@snu.ac.kr.

Abstract

BACKGROUND:

Somatic amplifications of the LYL1 gene are relatively common occurrences in patients who develop uterine corpus endometrial carcinoma (UCEC) as opposed to other cancers. This study was undertaken to determine whether such genetic alterations affect survival outcomes of UCEC.

METHODS:

In 370 patients with UCEC, we analysed clinicopathologic characteristics and corresponding genomic data from The Cancer Genome Atlas database. Patients were stratified according to LYL1 gene status, grouped as amplification or non-amplification. Heightened levels of cancer-related genes expressed in concert with LYL1 amplification were similarly investigated through differentially expressed gene and gene set enrichment analyses. Factors associated with survival outcomes were also identified.

RESULTS:

Somatic LYL1 gene amplification was observed in 22 patients (5.9%) with UCEC. Patients displaying amplification (vs. non-amplification) were significantly older at the time of diagnosis and more often were marked by non-endometrioid, high-grade, or advanced disease. In survival analysis, the amplification subset showed poorer progression-free survival (PFS) and overall survival (OS) rates (3-year PFS: 34.4% vs. 79.9%, P = 0.031; 5-year OS: 25.1% vs. 84.9%, P = 0.014). However, multivariate analyses adjusted for tumor histologic type, grade, and stage did not confirm LYL1 gene amplification as an independent prognostic factor for either PFS or OS. Nevertheless, MAPK, WNT, and cell cycle pathways were significantly enriched by LYL1 gene amplification (P < 0.001, P = 0.002, and P = 0.004, respectively).

CONCLUSIONS:

Despite not being identified as an independent prognostic factor in UCEC, LYL1 gene amplification is associated with other poor prognostic factors and correlated with upregulation of cancer-related pathways.

KEYWORDS:

Endometrial Neoplasms; Gene expression pattern analysis; Gene set enrichment analysis; LYL1s; Survival analysiss; The Cancer Genome Atlass

PMID:
29716549
PMCID:
PMC5930686
DOI:
10.1186/s12885-018-4429-z
[Indexed for MEDLINE]
Free PMC Article

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