Identification of Prognostic Signature Based on the Copy Number Variation (CNV) and Expression in Acute Myeloid Leukemia

Abstract

Purpose Acute myeloid leukemia (AML) is caused by multiple genetic alterations in the hematopoietic progenitors, and molecular genetic analysis has provided useful information for AML diagnosis and prognosis. However, an integrative understanding about the prognosis value of specific copy number variation (CNV) and CNV-modulated gene expression has been limited. Methods We conducted an integrative analysis of CNV profiling and gene expression using data from the TARGET and TCGA AML cohorts. The CNV data from TCGA were analyzed using the GISTIC. CNV survival analysis and mRNA survival analysis were conducted with the Multivariate Cox proportional hazards regression model using R software with “survminer” and “survival” packages. KEGG cancer panel genes were extracted from the cancer related pathways from Kyoto Encyclopedia of Genes and Genomes (KEGG). The R package “circlize” was used for mapping the CNV genes to chromosomes. Results From this investigation, we observed distinct CNV patterns in the AML risk groups as well as the expression of 251 genes significantly modulated by CNV in both cohorts. There were 102 CNV genes (located at 7q31-34, 16q24) associated with clinical outcomes in AML, which were identified in the TARGET cohort and validated in the TCGA cohort, three of which being miRNA genes (MIR29A, MIR183, MIR335) that overlapped with a KEGG cancer panel. Five genes were identified whose expressions were modulated by CNV and significantly associated with clinical outcomes, and among them, the deletion of SEMA4D and CBFB were found to potentially have protective effects against AML. Moreover, the distribution of CNV in these five CNV-modulated genes was independent of the risk groups, which suggests that they are independent prognosis factors. Conclusion Overall, this study identified 102 CNV genes and five CNV-modulated gene expressions that are crucial for developing new modes of prognosis evaluation and target therapy for AML.

Decreased complement 4d increases poor prognosis in patients with non‑small cell lung cancer combined with gastrointestinal lymph node metastasis

“…A dot plot was created based on the accuracy of the predictions, with different colors used to indicate correct and incorrect predictions, and to calculate the percentage correct. Statistical analyses were performed using RStudio (R version 3.5.0) with the following R packages: 'rms', 'ggplot2', 'risk regression', 'PredictABLE' and 'survminer' (20)(21)(22).…”

Class IV semaphorins in disease pathogenesis

“…Sema4D is associated with the etiology of various types of cancer 88,89 . Roles for Sema4D have been demonstrated in breast cancer, 90–101 colorectal carcer, 102–108 gastric cancer, 109 esophageal cancer, 110,111 lung cancer, 112–114 pancreatic cancer, 107,115–117 cholangiocarcinoma, 118 prostatic cancer, 119–123 bladder cancer, 124,125 kidney cancer, 125 cervical cancer, 126 ovarian cancer, 127–130 malignant melanoma, 131 osteosarcoma, 132 head‐and‐neck cancer, 133–137 medulloblastoma, 138 leukemia, 139–143 malignant lymphoma, 144 and multiple myeloma (Figure 4). 145 Cancer cells express Sema4D or its receptor, which are typically up‐ or down‐regulated in tumors compared to normal tissues.…”