College of Medicine, Gachon University, Incheon, Korea.
Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, Korea.
Sci Rep. 2019 Nov 18;9(1):16990. doi: 10.1038/s41598-019-53182-6.
Although colorectal cancer is one of the most lethal cancer types in the world, its metastasis to the ovary is rare, compared to metastasis to other organs. Consequently, the genomic basis for colon-to-ovary metastasis remains unstudied, due to limited available patients, and thus there have been no attempts to construct individual-specific networks. Due to its rarity, the small sample size makes common mutations difficult to find. To overcome this problem, we herein attempted to apply a biological connectivity map called a sample-specific network (SSN), to reveal common biological functions in three samples. Our three samples were compared to a clinical dataset contained in The Cancer Genome Atlas (TCGA) Colorectal Adenocarcinoma (COAD), showing different mutational spectra, compared to matched samples based on age, gender, microsatellite instability (MSI) status, and tumor, node, metastasis (TNM) stage. The SSNs for the three samples revealed significant correlations of the mutation statuses of several apoptosis genes, in contrast to the TCGA-matched samples. Further analysis of a targeted-gene panel sequencing dataset for colon-to-ovary metastasis of primary tumor samples also confirmed significant correlations of the mutational statuses among apoptosis genes. In summary, using SSN, we successfully identified a common function (apoptosis) among our three patients having colon-to-ovary metastasis, despite no common mutations in the three patients. Such computational analyses could facilitate productive study of rare cancers and other diseases.
尽管结直肠癌是世界上最致命的癌症类型之一，但与转移至其他器官相比，其转移至卵巢的情况较为罕见。因此，由于可获得的患者有限，因此尚未对结肠癌至卵巢转移的基因组基础进行研究，也没有尝试构建个体特异性网络。由于其罕见性，小样本量使得常见突变难以发现。为了解决这个问题，我们在此尝试应用一种称为样本特异性网络（SSN）的生物连通性图谱，以揭示三个样本中的常见生物学功能。我们的三个样本与包含在癌症基因组图谱（TCGA）结直肠腺癌（COAD）中的临床数据集进行了比较，与基于年龄、性别、微卫星不稳定性（MSI）状态和肿瘤、淋巴结、转移（TNM）分期的匹配样本相比，显示出不同的突变谱。三个样本的 SSN 显示出几个凋亡基因的突变状态存在显著相关性，与 TCGA 匹配的样本相比。对原发性肿瘤样本的靶向基因面板测序数据集进行的进一步分析也证实了凋亡基因之间的突变状态存在显著相关性。总之，使用 SSN，我们成功地鉴定了三个患有结肠癌至卵巢转移的患者之间的共同功能（凋亡），尽管这三个患者中没有共同的突变。这种计算分析可以促进对罕见癌症和其他疾病的有成效的研究。
