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Abstract

BACKGROUND:

Nearly half of adult acute myeloid leukemia (AML) patients were classified into cytogenetic normal acute myeloid leukemia (CN-AML). The expression level of Trophinin associated protein (TROAP) was proven to be associated with the prognosis of several cancers, but it is still unclear in the prognosis of patients with CN-AML.

METHODS:

We integrated CN-AML patient samples from 4 datasets to analyze the relationship between TROAP expression and the survival of CN-AML. In addition, we investigated 92 AML patients of The Cancer Genome Atlas (TCGA) database to analyze the relationship between TROAP expression and the survival of AML patients received chemotherapy. We investigated the relationship between the expression of TROAP and drug sensitivity in AML cell lines.

RESULTS:

CN-AML patients with high TROAP expression were related to good event-free survival (EFS) and overall survival (OS). In AML patients received chemotherapy, high TROAP expression was associated with good survival prognosis. Additionally, the expression of TROAP gene in leukemia stem cells (LSC) $+$ group was lower. Among multiple drugs, the lower the expression of TROAP, the lower the IC50.

CONCLUSION:

TROAP could serve as an independent predictor of CN-AML patients and could act as a potential biomarker for the prognosis of CN-AML. TROAP expression levels were closely correlated with the drug sensitivity of multiple drugs.

Keywords

TROAP acute myeloid leukemia cytogenetic type prognosis

1. Background

Acute myeloid leukemia (AML) is a heterogeneous malignant disease that is classified by the abnormal proliferation of progenitor cells without the ability to differentiate [1]. Myeloid leukemogenesis driven by many genomic alterations is related to chromosome aberrations, such as reciprocal translocation, insertions, deletions, inversions, trisomies and monosomies [2]. Exploration of complexity of heterogeneity has been demonstrated that some certain chromosomal abnormalities could suggest the prognosis of patients who have received standard treatment (anthracycline and ara-C). However, a subgroup of AML patients (20% of pediatric and 45% of adult AML cases) [3] without any cytogenetic abnormalities is defined as cytogenetically normal acute myeloid leukemia (CN-AML). Characterized by intermediate-risk category [4], identifying novel prognostic determinants in patients with CN-AML has performed challenges.

In 14 AML patients with normal karyotype, 19 AML-associated mutated genes were detected by NGS, and only 9 mutations were found, including: DNMT3A, IDH2, IDH1, NRAS, NPM1, TET2, ASXL1, PTPN11, and RUNX1 [5]. According to different gene mutation combinations of CN-AML patients, the prognosis could be further predicted. For instance, mutations in CEBPA and NPM1 are associated with a good prognosis in CN-AML [6, 7], while DNMT3A, TET2, and RUNX1 mutations are associated with poor prognosis in CN-AML [8, 9, 10]. Besides, high expression of some genes including ITPR2, MAPKBP1, CPNE3, RUNX1 and ATP1B1 are associated with poor prognosis of CN-AML, while the high expression of LEF1 is regarded as a favorable prognostic factor for CN-AML [11, 12, 13, 14, 15, 16]. Therefore, the identification of new potential biomarkers can help further predict the prognosis risk of CN-AML.

Trophinin-associated protein (TROAP), formally known as tastin, was a protein first identified to mediate human embryo implantation and found to be related to microtubule regulation later. TROAP is a cytoplasmic protein that forms a complex with trophinin and bystin to mediate the initial attachment in the interface of trophoblasts and endometrium [17, 18, 19, 20, 21, 22]. This complex function in the cellular process of embryo implantation, which is accompanied by malignant tumor cell invasion and metastasis. Previous studies revealed that TROAP expression is located in the centrosomes, microtubules and the proper spindle during the mitosis. High level of TROAP mediates the formation of unipolar spindles. The loss of TROAP expression will lead to induction of multipolar spindles and mitotic blockade, indicating that TROAP has significance in proper spindle assembly [23, 24, 25].

Recently, some researchers have found that TROAP play a critical role in several cancers including gastric cancer [26], epithelial ovarian carcinoma [27, 28], colorectal cancer [29], prostate cancer [30], and hepatocellular carcinoma [31, 32]. However, the role of TROAP in the progression of heterogeneous malignant disease, especially the prognostic significance of TROAP expression in AML, remains unclear. In our study, through an analysis of data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we investigated potential correlations between the expression of TROAP in patients with CN-AML and prognosis of cytogenetically normal acute myeloid leukemia and assessed the prognostic value of TROAP for event-free survival (EFS) and overall survival (OS) of CN-AML patients.

2. Methods

2.1 Data source

In our study, we detected the TROAP expression level of CN-AML patients from TCGA and GEO databases (including GSE12417, GSE22778, GSE71014 datasets) [33, 34, 35, 36]. We analyzed the relationship between survival and TROAP expression through 75 CN-AML patients from TCGA database. Moreover, the analysis of relationship between TROAP expression and OS from GSE12417 (78 patients from GSE12417 U133 plus dataset, 162 patients from GSE12417 U133A dataset), GSE22778 (55 patients from GSE22778 GPL8653 dataset), and GSE71014 datasets (104 patients from GSE71014 dataset) were done. In the TCGA database, 92 patients with AML received chemotherapy were received analysis of the correlation between TROAP gene and survival (OS and EFS). We also analyzed relationship between TROAP expression and OS in 417 newly diagnosed AML patients from GSE37642 GPL96 [37]. By using the GSE76004 dataset [38], we examined 227 CD34/CD38 cell fractions from samples of 78 AML patients and detected TROAP expression of each group. Besides, we detected TROAP gene expression of those patients in different LSC activity groups (Supplementary Fig. 1). Meanwhile, we did univariate and multivariate analysis for EFS and OS of 75 CN-AML patients from TCGA dataset. The risk classification of TCGA 75 CN-AML patients are based on 2010 European Leukemia Net (ELN) guideline. We investigated the expression of TROAP of 29 tumor tissues and normal tissues, normal tissues from GTEx, and normal hematopoiesis cells from GSE42519 [39, 40, 41]. We also analyzed the dependence of cell lines of 23 tumor on TROAP using RNAi (Achilles $+$ DRIVE $+$ Marcotte, DEMETER2) dataset of DepMap Portal database (https://depmap.org/portal/). Data from Genomics of Drug Sensitivity in Cancer (GDSC) were used to study the relationship between TROAP expression level and 50% inhibiting concentration (IC50; https://www.cancerrxgene.org/).

The informed consents of this research were consistent with the Ethics Committee of Peking University Third Hospital and did not violate the Declaration of Helsinki. All persons gave their informed consent prior to their inclusion in the study.

The 75 CN-AML were selected from TCGA database with the criteria as follows: 1) AML patient with normal karyotype. 2) All patients received gene expression detection with RNA-seq. 3) AML patients received chemotherapy regimen or transplant regimen.

The 92 AML received chemotherapy were selected from TCGA database with the criteria as follows: 1) AML patients received chemotherapy regimen but not transplant regimen. 2) All patients received gene expression detection with RNA-seq. 3) AML patients with normal or abnormal karyotype.

2.2 Gene expression analysis

We calculated the RNA expression from RNA-seq data of TCGA dataset using RPKM (Reads Per Kilobase per Million mapped reads). We calculated the RNA expression from microarray of each AML sample from GEO databases by using the method of RMA (robust multiarray averaging). Then, the value of TROAP expression level of each gene was further transformed with log2. The $P$ -value of EFS and OS for all the genes of RNA-seq from TCGA CN-AML dataset was calculated and the TROAP was on the top rank through the rank of $P$ -value. Through using the method of maximally selected rank statistics algorithm, which means calculating all cut-off value and their effect for influencing survival and choosing the value that distinguishes patients into two groups best, we divided CN-AML patients into high-TROAP group and low-TROAP group. The endpoints of clinical event are EFS and OS. The definition of EFS is the time length from diagnosis to the first event, including last visit, no complete remission and relapse. Similarly but differently, OS is defined as the time length from diagnosis to the last follow-up or the death for any reason.

2.3 Statistics

Through using R software v3.1.3 (ggplot2 and survminer v0.4.6 package), we finished statistical analysis in this research. Meanwhile, we used Kaplan-Meier estimation to plot survival curves and present survival analysis by the log-rank test. One-way analysis of variance (Anova test) was used in comparing TROAP expression levels between four CD34/CD38 subgroups. Additionally, we adopted unpaired $t$ test to compare the expression level of TROAP between the LSC $-$ and LSC $+$ groups. For quantitative variables, we used unpaired $t$ test to finish statistical analysis. The Fisher’s exact test was applied in comparing qualitative baseline characteristics, which contained two and over two groups (Supplementary Table 1). Univariate and multivariate Cox analysis was adopted to analyze the correlation of TROAP expression on other clinical features (age, WBC, PB_BLAST, mutation of famous genes, etc.) and survival (Table 1 and Supplementary Fig. 2). $P$ value $<$ 0.05 was regarded statistically significant in all statistical methods.

Table 1
Multivariate analysis for TCGA CN-AML patients’ EFS and OS

	HR	Lower	Upper	$P$ -value
Variables		95% CI for HR
EFS
DNMT3A	1.815	0.989	3.331	0.054
FLT3	1.574	0.853	2.905	0.147
TROAP	0.496	0.268	0.921	0.026
OS
DNMT3A	1.853	1.021	3.362	0.042
Age	1.845	1.030	3.303	0.039
TROAP	0.381	0.208	0.698	0.002

HR, hazard ratio; CI, confidence interval. TROAP (TROAP gene expression, high vs. low expression). DNMT3A (mutation vs. wild type), FLT3 (mutation vs. wild type).

Figure 1.

High TROAP expression predicts better survival of cytogenetic normal acute myeloid leukemia (CN-AML) and AML patients received chemotherapy from the TCGA database. The X axis represents time (months) and the Y axis represents survival probability. A, Kaplan-Meier curves for event-free survival (EFS) and overall survival (OS) in different TROAP expression groups of CN-AML in the TCGA database (Cut off value $=$ 8.44). EFS, $P=$ 0.0032; OS, $P=$ 0.00025; log-rank test. B, Kaplan-Meier curves of EFS and OS in different TROAP expression group received chemotherapy (Cut off value $=$ 8.19). EFS, $P=$ 0.048; OS, $P=$ 0.0046; log-rank test.

3. Results

3.1 Clinical baseline characteristics of patients with CN-AML from TCGA database

We divided 75 CN-AML patients into TROAP-high group and TROAP-low group based on TROAP expression level (see method for the standard of each group). Then we compared the molecular and clinical characteristics of two groups (Supplementary Table 1). WBC of TROAP-low group was higher than the group of high TROAP expression ( $P<$ 0.001; unpaired $t$ test). Besides, patients in TROAP-low group had more KRAS gene mutation than the group of high TROAP expression ( $P=$ 0.043; Fisher’s exact test). The difference in baseline characteristics of clinical between the two different groups was not statistically significant including race, sex, FAB subtypes, induction, relapse, transplant, complete response, relapse before transplantation and other gene mutations (NPM1, DNMT3A, TET2, and so on) (all $P>$ 0.05; Fisher’s exact test). We also found the difference in bone marrow blast, age, and peripheral blood blast between the two different groups was not statistically significant (all $P>$ 0.05; unpaired $t$ test).

Figure 2.

High TROAP expression predicts better survival of CN-AML patients from the other independent datasets. The X axis represents time (days) and the Y axis represents survival probability. A, (left side) Kaplan-Meier curves of OS in different TROAP expression groups of CN-AML in GSE12417 U133 plus (Cut off value $=$ 7.3). OS, $P=$ 0.19; log-rank test; (right side) Kaplan-Meier curves of OS in different TROAP expression groups of CN-AML in GSE12417 U133A dataset (Cut off value $=$ 8.87). OS, $P=$ 0.047; log-rank test. B, (left side) Kaplan-Meier curves of OS in different TROAP expression groups of CN-AML in GSE22778 GPL8653 dataset (Cut off value $=-$ 1.08). OS, $P=$ 0.19; log-rank test; (right side) Kaplan-Meier curves of OS in different TROAP expression groups of CN-AML in GSE71014 dataset (Cut off value $=$ 6.36). OS, $P=$ 0.0092; log rank test.

Figure 3.

Expression level of TROAP gene in LSC. The X axis represents different group of AML cells and the Y axis represents gene expression. TROAP gene expression was transformed as log2. A, Comparison of TROAP expression levels in four subtypes of AML cells, $P=$ 0.00019; ANOVA, ns, ${}^{****}$ indicate $P>$ 0.05 and $P\leqslant$ 0.0001, respectively. Each group is compared to the average of the entire data. B, Low expression level of TROAP gene in LSC $+$ . $P=$ 0.0021; unpaired $t$ test.

3.2 Survival rate of the high level of TROAP in patients with CN-AML was better

In our study, we examined the relationship between the different levels of TROAP gene expression and survival (including OS and EFS) from samples of 75 TCGA patients with normal karyotypes AML. The EFS and OS of group of high level of TROAP gene expression was better than the group of low level of TROAP (Fig. 1A, EFS, $P=$ 0.0032; OS, $P=$ 0.00025; log-rank test). The relationship between TROAP gene expression and the OS of 104 patients from GSE71014 CN-AML was examined and we found a similar result. The OS of group of high level of TROAP gene expression was better than low TROAP expression significantly (Fig. 2B (right side), OS, $P=$ 0.0092; log-rank test). Besides, the OS of group of high level of TROAP gene expression was better than the group of low TROAP gene expression in other independent datasets such as GSE12417 U133A dataset including 162 CN-AML patients (Fig. 2A (right side), OS, $P=$ 0.047; log-rank test). 78 patients with normal karyotypes AML from GSE12417 U133 plus data (Fig. 2A (left side)) and 55 CN-AML patients from GSE22778 GPL8653 dataset (Fig. 2B (left side)) also have similar trends. In addition, we also found that TROAP expression was associated with better OS in 417 newly diagnosed AML patients from GSE37642 (Fig. S3A, OS, $P=$ 0.043; log-rank test).

3.3 TROAP expression predicts survival received chemotherapy in AML patients

To research the expression level of TROAP in AML patients received chemotherapy, we investigated the correlation of the gene expression of TROAP and the prognostic value of 92 received chemotherapy patients from TCGA database. By analyzing the EFS and OS in TROAP-high and TROAP-low groups of 92 CN-AML received chemotherapy patients, we found that the high expression of TROAP predicts better survival rate (Fig. 1B, EFS, $P=$ 0.048; OS, $P=$ 0.0046; log-rank test). This result proved that the TROAP gene predicts better prognosis in CN-AML patients received chemotherapy.

3.4 Expression level of TROAP in LSC

Leukemia Stem Cells (LSC) were divided into 4 cell populations according to fractions of the CD34 and CD38 phenotypes. The expression level of TROAP was significantly different in each subgroup (Fig. 3A, $P=$ 9.2e-06; Anova test). Compared with the average value of all subgroups, the expression of TROAP gene decreased in the CD34 $+$ /CD38 $-$ group (Fig. 3A, $P\leqslant$ 0.001; unpaired $t$ test). To detect the expression level of TROAP gene in LSC, we analyzed 78 AML patients’ samples from the GSE76004 dataset. The data suggested that the expression of TROAP gene in LSC $+$ group was lower than in LSC $-$ group (Fig. 3B, $P=$ 0.0021; unpaired $t$ test).

3.5 Univariate and multivariate analysis of TCGA CN-AML patients’ EFS and OS

Age ( $\geqslant$ 60 vs. $<$ 60 years), BM-blast ( $\geqslant$ 70 vs. $<$ 70%), WBC count ( $\geqslant$ 30 vs. $<$ 30 $\times$ 10 ${}^{9}$ /L), PB-blast ( $\geqslant$ 50 vs. $<$ 50%), TROAP expression level (high and low), and common leukemia-associated genes (DNMT3A, NPM1, TET2, FLT3, IDH2, IDH1, RUNX1, NRAS, WT1, CEBPA, PTPN11, KRAS, Mutation vs. WT) were selected for univariate analysis (Supplementary Fig. 2). Univariate analysis showed that DNMT3A and FLT3 were related to worse EFS, and DNMT3A and age were associated to worse OS, while TROAP expression was closely associated with better EFS and OS.

We selected TROAP expression levels, age $\geqslant$ 60, and mutated DNMT3A, FLT3 genes for multivariate analysis of TCGA CN-AML patients’ EFS and OS (Table 1). Multivariate analysis illustrated independent risk factors for TCGA CN-AML patients’ EFS and OS. Low TROAP expression was associated with worse EFS (TROAP, $P=$ 0.026; Cox regression). Low TROAP expression, age $\geqslant$ 60 and DNMT3A mutations were significantly related with OS (TROAP, $P=$ 0.002; Age, $P=$ 0.039; DNMT3A, $P=$ 0.042; Cox regression). Among them, TROAP expression is the best survival predictor of CN-AML patients.

3.6 TROAP expression level in various tumors, normal tissue, and hematopoiesis cell

We studied the expression levels of TROAP of 29 tumors and normal tissue from TCGA and Genotype-Tissue Expression (GTEx, Fig. S4A and B). We discovered that in most solid tumors, the expression level of TROAP in normal tissue was lower than in tumor tissue, while in AML, we found that the expression level of TROAP was higher in normal bone marrow than in tumor tissue. (Fig. S4A, $P<$ 0.0001, unpaired $t$ -test; Fig. S4B, $P<$ 2.2e-16, Kruskal-Wallis test). In addition, we further studied the expression levels of TROAP in normal hematopoiesis cells from GSE42519. We discovered that in normal hematopoietic cells, the expression level of TROAP of myelocyte was significantly higher than that in other cells (Fig. S5A, $P=$ 0.00099, Kruskal-Wallis test). Cell lines from 23 tumors from the RNAi (Achilles $+$ DRIVE $+$ Marcotte, DEMETER2) dataset of DepMap Portal database were analyzed and TROAP was more likely to be required for leukemia (Fig. S6A) [42].

3.7 Relationship between the expression level of TROAP and drug sensitivity

To further investigate whether TROAP expression level is related to drug sensitivity, we compared the IC50 values of compounds in the high and low expression groups of TROAP in GDSC 20 AML cell lines. We found significant differences in IC50 between high-TROAP and low-TROAP among 5 drugs including 5-Fluorouracil, LGK974, Irinotecan, Luminespib and Camptothecin (Fig. S7A). 5-Fluorouracil, Camptothecin and Irinotecan are antitumor chemotherapeutic agents used in the treatment of many types of cancer including AML [43]. We found that among the three drugs (5-Fluorouracil, Camptothecin, Irinotecan), the lower the expression of TROAP, the lower the IC50, and the higher the sensitivity to the drugs (Fig. S7B–D; 5-Fluorouracil, $P=$ 0.041; Camptothecin, $P=$ 0.029; Irinotecan, $P=$ 0.045; unpaired $t$ -test). This finding may help us to better understand the mechanism of the three classes of drugs for AML. LGK974 that targets a Wnt-specific acyltransferase and Luminespib that is a potent and selective HSP90 inhibitor are being developed to treat cancer [44, 45]. We found that in LGK974 and Luminespib, the lower the expression level of TROAP, the higher the drug sensitivity, and it might imply they had an effect on AML patients with low TROAP expression (Fig. S7E and F; LGK974, $P=$ 0.037; Luminespib, $P=$ 0.048; unpaired $t$ -test).

4. Discussion

An array of adhesion proteins, including L-selectin and trophinin, mediate human embryo implantation [46]. As a cytoplasmic protein, TROAP forms a complex with trophinin and bystin intracellular domain to mediate the interaction between trophoblast cell and endometria cell. After the elementary attachment of the maternal epithelial cells to embryonic cells, an intensive adhesion is induced, and a series of morphological changes are found in the embryo implantation site. The cellular process of embryo implantation may be related to the cell process of malignant tumor cells in invasion and metastasis, which infers that the expression of TROAP gene may be associated with malignant tumors [24, 25, 47].

In previous studies, high TROAP expression has been reported in some malignant solid tumors such as gastric cancer [26], colorectal cancer [29], prostate cancer [30], epithelial ovarian carcinoma [28] and liver cancer [48]. In some solid cancers, like gastric cancer, colorectal cancer, prostate cancer [26, 29, 30], TROAP gene was upregulated compared to the normal counterparts. Besides, TROAP gene promoted cell proliferation, G1 to S cell cycle transition and the ability of migration and invasion of tumor cells, which predicted poor survival significantly. Moreover, in the epithelial ovarian carcinoma, the expression product of TROAP is helpful to predict the stage of malignant tumor. More TROAP genes were expressed in later stage of epithelial ovarian carcinoma [28]. However, some report showed that downregulated TROAP plays a critical role in human hepatocellular carcinoma through upregulation of tumor cell growth and migration [31], which suggested that TROAP is a prognostic biomarker for these hepatocellular cancer patients. These conclusions proved that the prognostic results of TROAP were different in different cancers. In most solid cancers, TROAP gene predicts a poor prognosis in survival. So far, we seldom have known about the relationship between TROAP and none-solid tumors. Importantly, the prognostic relationship between this gene and CN-AML, an intermediate-risk category, has not been researched recently. We analyzed the gene expression of TROAP from CN-AML patients in 4 independent datasets to prove that the correlation of TROAP gene expression and prognosis of CN-AML patients and this gene is an independent risk factor of CN-AML. In our survival analysis research, we showed that the CN-AML patients with high expression of TROAP had better prognosis than those with low TROAP expression. High TROAP expression also predicts good prognosis in AML patients received chemotherapy. The possible mechanism for the better prognosis of high TROAP expression AML patients may be related to the LSC. Lower TROAP expression was observed in LSC $+$ compared with LSC $-$ group. These results indicated that TROAP predicts different prognosis in non-solid malignant tumors from most solid tumors.

CD34 $+$ CD38 $-$ is the immunophenotype of LSC in AML [49, 50]. A few of CD34 $-$ and most of CD34 $+$ fractions contained LSC, and LSCs were found in all CD34/CD38 phenotype fractions [38, 51]. AML is originated by a small fraction of LSCs that are associated with proliferation and unrestricted self-renewal in leukemia mother cells, resulting in chemoresistance and relapse [52, 53]. High expression of LSC gene is independently related to poor prognosis in patients with AML [54]. Therefore, developing prognostic biomarkers related to stemness is necessary. In our research, lower TROAP gene expression was present in AML patients with LSC $+$ , inferring that the TROAP gene is scarce in stem cell expression. This result showed that the TROAP might affect LSC negatively.

In the multivariate analysis, we discovered that age and the DNMT3A mutation were related to EFS and OS in CN-AML patients, and that the FLT3 mutation was associated with EFS in CN-AML. Besides, TET2 and NRAS mutations were related to OS in CN-AML patients. Those results showed consistency with previous findings that DNMT3A mutations are associated with shorter EFS and OS [55, 56]. Multivariate analysis showed that high expression of TROAP in CN-AML patients was regarded to be associated with better OS. Furthermore, we found that the correlation between TROAP expression levels and the prognosis of CN-AML patients was better than other factors. These results indicated that TROAP was an independent predictor of clinical prognosis in patients with CN-AML.

However, we have not researched the specific function of TROAP in the pathogenesis-signaling pathway of CN-AML. This study only investigated the expression of individual genes, and future studies combining other different types of biomarkers could predict the prognosis of patients with CN-AML better. Meanwhile, we did not apply data of TROAP expression and clinical pathologic variables to build a predictive model because of the limited number of samples. In our future work, we will investigate the potential clinical prognostic value of TROAP expression in a larger population for constructing a proper predictive model for the prognosis of patients with CN-AML.

5. Conclusions

The present study indicated that high expression of TROAP gene was a better prognostic factor for CN-AML patients and AML patients received chemotherapy. TROAP could serve as an independent predictor of CN-AML patients and act as a potential biomarker for the prognosis of CN-AML patients and AML patients. The expression level of TROAP is closely related to drug sensitivity.

List of abbreviations

AML: acute myeloid leukemia; CN-AML: cytogenetically normal acute myeloid leukemia; TROAP: Trophinin-associated protein; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; EFS: event-free survival; OS: overall survival; LSC: leukemia stem cells; BM-blast: bone marrow blast; PB-blast: peripheral blood blast; WBC: white blood cell; HR: hazard ratio; CI: confidence interval.

Ethics approval and consent to participate

All experimental protocols were approved by a Ethics Committee of Peking University Third Hospital and did not violate the Declaration of Helsinki. All persons gave their informed consent prior to their inclusion in the study.

Consent for publication

Not applicable.

Availability of data and materials

Not applicable.

Competing interests

The authors declare no competing interests.

Funding

This work was funded by National Natural Science Foundation of China (81800195), interdisciplinary medicine Seed Fund of Peking University (BMU2018MB004), Natural Science Foundation of Beijing Municipality (7132183 and 7182178), China Health Promotion Foundation (CHPF-zlkysx-001), and Key Clinical Projects of Peking University Third Hospital (BYSYZD2019026).

Authors’ contributions

HMJ and WLZ made contributions to conception of the project. HX, JH, CJY, and WLZ make contributions to interpretation or analysis of data. HX, JH, JCY, NXL, YLZ, PY, JW, SXL, WZ, GHD, WLZ and HMJ contribute to preparation of the manuscript and revision for important intellectual content. HMJ and WLZ make contributions to supervision of the project. All authors read and approved the final manuscript.

Supplementary data

The supplementary files are available to download from http://dx.doi.org/10.3233/CBM-210042.

sj-pdf-1-cbm-10.3233_CBM-210042.pdf - Supplemental material

Supplemental material, sj-pdf-1-cbm-10.3233_CBM-210042.pdf

sj-docx-1-cbm-10.3233_CBM-210042.docx - Supplemental material

Supplemental material, sj-docx-1-cbm-10.3233_CBM-210042.docx

Footnotes

Acknowledgments

The authors thank TCGA database and datasets GSE12417, GSE22778, GSE71014, GSE76004, GSE37642, GSE42519 from GEO database, GDSC database, DepMap Portal database and GTEx database.

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High trophinin-associated protein expression predicts good survival in acute myeloid leukemia with normal cytogenetics

Abstract

BACKGROUND:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Background

2. Methods

2.1 Data source

2.2 Gene expression analysis

2.3 Statistics

Table 1 Multivariate analysis for TCGA CN-AML patients’ EFS and OS

3.1 Clinical baseline characteristics of patients with CN-AML from TCGA database

3.3 TROAP expression predicts survival received chemotherapy in AML patients

3.4 Expression level of TROAP in LSC

3.5 Univariate and multivariate analysis of TCGA CN-AML patients’ EFS and OS

3.6 TROAP expression level in various tumors, normal tissue, and hematopoiesis cell

3.7 Relationship between the expression level of TROAP and drug sensitivity

4. Discussion

5. Conclusions

List of abbreviations

Ethics approval and consent to participate

Consent for publication

Availability of data and materials

Competing interests

Funding

Authors’ contributions

Supplementary data

sj-pdf-1-cbm-10.3233_CBM-210042.pdf - Supplemental material

sj-docx-1-cbm-10.3233_CBM-210042.docx - Supplemental material

Footnotes

Acknowledgments

References

Table 1
Multivariate analysis for TCGA CN-AML patients’ EFS and OS