The high-risk model associated with SYTL4 predicts poor prognosis and correlates with immune infiltration in AML

Abstract

Acute myeloid leukemia (AML) currently lacks a definitive cure. Studies have highlighted the involvement of SYTL4 expression levels in neoplasms, yet its specific roles in AML remain unexplored in the literature. Utilizing the TCGA and XENA databases, this study investigated SYTL4 expression levels in AML and identified associations between SYTL4 overexpression and clinicopathological features, prognosis, and immune infiltration in AML patients through genomic analysis. ROC analysis demonstrated the diagnostic value of SYTL4 overexpression in AML. Kaplan-Meier survival, Cox regression, and Lasso analyses were employed to explore SYTL4-coexpressed long non-coding RNAs linked to AML patient prognosis, alongside the construction of nomograms and risk models. SYTL4 expression was significantly elevated in AML and correlated with FAB classification, cytogenetic risk, IDH1 R140 mutation, and NPM1 mutation in cancer patients. SYTL4 overexpression signaled a poor prognosis, serving as a risk indicator for assessing adverse outcomes in AML patients. SYTL4 expression levels also correlated with AML immune cell levels and markers. COX regression analysis revealed that LINC01700, CPNE8-AS1, HOXA10-AS, LINC00899, and SYTL4 influenced adverse AML prognosis. Patients in the high-risk group for these factors experienced significantly poor outcomes, which were closely associated with aDC, CD8 T cells, and TH17 cells. In summary, SYTL4 overexpression is linked to poor prognosis and immune infiltration in AML, with the constructed risk model intended as a prognostic evaluation tool for AML patients.

Keywords: Acute myeloid leukemia; Genomics; Nomograph; Risk model; SYTL4; lncRNAs.

Fig. 1

SYTL4 was overexpressed in AML. (A) Normal vs AML; (B) M0 vs M2; (C) M0 vs M3; (D) M0 vs M4; (E) M1 vs M3; (F) M2 vs M3; (G) M3 vs M4; (H) M3 vs M5; (I) Favorable vs Intermediate. Note: AML, acute myeloid leukemia.

Fig. 2

SYTL4 overexpression was associated with the prognosis in AML patients. (A) Median value; (B) Tertile value; (C) quartile value; (D) Quintile value; (E) The best P value. Note: AML, acute myeloid leukemia.

Fig. 3

SYTL4 overexpression in patients with was associated with dismal prognosis in AML patients based on the subgroup analysis. (A) Male; (B) Female; (C) Caucasian; (D) Age ( ≤ 60); (E) White blood cell count ( ≤ 20 × 10^9/L); (F) White blood cell count (>20 × 10^9/L); (G) BM blast ( ≤ 20 %); (H) BM blast (>20 %); (I) PM blast ( ≤ 70 %); (J) PM blast (>70 %); (K) Cytogenetic risk (intermediate); (L) FLT3 mutation (Negative). Note: AML, acute myeloid leukemia.

Fig. 4

The prognostic values of SYTL4 expression at 1–6 year OS in AML. Note: AML, acute myeloid leukemia; OS, overall survival.

Fig. 5

SYTL4-related prognostic nomogram in AML. Note: AML, acute myeloid leukemia.

Fig. 6

SYTL4 expression was correlated with the levels of immune cell infiltration in AML. (A) CD8 T cells; (B) T helper cells; (C) NK CD56dim cells; (D) TFH; (E) Th1 cells; (F) Cytotoxic cells; (G) NK cells; (H) NK CD56bright cells; (I) aDC. Note: AML, acute myeloid leukemia.

Fig. 7

The expression levels of immune cells in high- and low- SYTL4 expression groups in AML. Note: AML, acute myeloid leukemia.

Fig. 8

SYTL4 expression correlated with the levels of immune cell markers in AML. (A) LAG3; (B) KIR2DL3; (C) KIR2DL4; (D) KIR3DL2; (E) KIR2DL1; (F) KIR3DL1; (G) GZMB; (H) KIR2DS4; (I) TBX21. Note: AML, acute myeloid leukemia.

Fig. 9

The prognostic values of SYTL4 associated lncRNAs. (A) AC096677.1; (B) AC135507.1; (C) AC246787.2; (D) AL023284.4; (E) AL359094.1; (F) AL359094.1; (G) CPNE8-AS1; (H) HOXA10-AS; (I) LINC00899; (J) LINC01106; (K) LINC01694; (L) LINC01700.

Fig. 10

The prognostic nomogram of SYTL4 associated lncRNAs.

Fig. 11

SYTL4 associated risk model correlated with the prognosis in AML. Note: AML, acute myeloid leukemia.

Fig. 12

SYTL4 associated risk model significantly correlated with immune cell levels. (A) aDC; (B) CD8 T cells; (C) iDC; (D) pDC.