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. 2024 Jun 6;16(11):9784-9812.
doi: 10.18632/aging.205899. Epub 2024 Jun 6.

Overexpression of zinc finger DHHC-type containing 1 is associated with poor prognosis and cancer cell growth and metastasis in uterine corpus endometrial carcinoma

Ni Jiang  1 , Dan Li  2 , Ye Han  1 , Zhi-Guo Luo  2 , Lu-Bin Liu  1
Affiliations

Overexpression of zinc finger DHHC-type containing 1 is associated with poor prognosis and cancer cell growth and metastasis in uterine corpus endometrial carcinoma

Ni Jiang et al. Aging (Albany NY). .

Abstract

The zinc finger DHHC-type containing 1 (ZDHHC1) gene is implicated in the pathogenesis and progression of various malignant tumors, but its precise involvement in uterine corpus endometrial carcinoma (UCEC) remains unknown. Thus, this study investigated ZDHHC1 expression in UCEC using publicly available TCGA and Xena databases and elucidated the functions and mechanisms of the ZDHHC1 gene in UCEC progression using bioinformatics and in vitro experiments. The correlation between ZDHHC1 expression and prognosis, clinical features, immune cells, and RNA modifications of UCEC was evaluated using nomograms, correlation, ROC, and survival analyses. The impacts of ZDHHC1 overexpression on UCEC progression and mechanisms were explored with bioinformatics and in vitro experiments. Our study revealed that ZDHHC1 expression was significantly downregulated in UCEC and correlated with poor prognosis, cancer diagnosis, clinical stage, age, weight, body mass index, histological subtypes, residual tumor, tumor grade, and tumor invasion. Notably, Cox regression analysis and constructed nomograms showed that downregulated ZDHHC1 expression was a prognostic factor associated with poor prognosis in patients with UCEC. Conversely, above-normal ZDHHC1 expression inhibited the cell growth, cell cycle transition, migration, and invasion of UCEC cells, which may be related to the cell cycle, DNA replication, PI3K-AKT, and other pathways that promote tumor progression. Altered ZDHHC1 expression in UCEC was significantly associated with RNA modifications and the changes in cancer immune cell populations, such as CD56 bright NK cells, eosinophils, Th2 cells, and cell markers. In conclusion, considerably reduced ZDHHC1 expression in UCEC is associated with cancer cell growth, metastasis, poor prognosis, immune infiltration, and RNA modifications, revealing the promising potential of ZDHHC1 as a prognostic marker for UCEC.

Keywords: RNA modification; UCEC; ZDHHC1; immune infiltration; nomogram.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to this study.

Figures

Figure 1
Figure 1
ZDHHC1 expression in normal endometrial and UCEC tissues. (A) TCGA database. (B) Xena database. (C) TCGA database. Abbreviations: UCEC: uterine corpus endometrial carcinoma; ZDHHC1: zinc finger DHHC-type containing 1; TCGA: The Cancer Genome Atlas; GTEx: Genotype-Tissue Expression.
Figure 2
Figure 2
ZDHHC1 expression in UCEC tissues derived from TCGA database. (A) Tumor stage I–II vs. III–IV. (B) Age ≤60 vs. >60. (C) Weight ≤80 vs. >80. (D) BMI ≤30 vs. >30. (E) Endometrioid vs. mixed. (F) Endometrioid vs. serous. (G) Mixed vs. serous. (H) R0 vs. R2. (I) R1 vs. R2. (J) G1 vs. G3. (K) G2 vs. G3. (L) Tumor invasion (%) ≤50 vs. >50. (M–O) Alive vs. deceased. Abbreviations: UCEC: uterine corpus endometrial carcinoma; ZDHHC: zinc finger DHHC-type containing 1; TCGA: The Cancer Genome Atlas; BMI: body mass index; R0-R2: residual tumor; G1-G3: histopathologic grading.
Figure 3
Figure 3
ZDHHC1 expression is related to diagnosis and prognosis in UCEC. (A, B) The diagnostic values of ZDHHC1 in UCEC obtained from TCGA and GTEx data in Xena database. (C–E) The prognostic values of ZDHHC1 in UCEC calculated from TCGA data. Abbreviations: UCEC: uterine corpus endometrial carcinoma; ZDHHC1: zinc finger DHHC-type containing 1; TCGA: The Cancer Genome Atlas; GTEx: Genotype-Tissue Expression.
Figure 4
Figure 4
ZDHHC1 expression is associated with poor survival in subgroups of patients with UCEC. (A) Tumor stage I–III. (B) Black or African American. (C) White. (D) CR. (E) Age ≤60. (F) Age >60. (G) Weight >80 kg. (H) Height ≤160 cm. (I) Height >160 cm. (J) BMI >30. (K) Histological type of endometrioid. (L) R0. (M) Without hormone therapy. (N–O) With/without diabetes. (P, Q) With/without radiation therapy. Abbreviations: UCEC: uterine corpus endometrial carcinoma; ZDHHC1: zinc finger DHHC-type containing 1; CR: complete response; BMI: body mass index.
Figure 5
Figure 5
ZDHHC1 expression is related to disease-specific survival in subgroups of patients with UCEC. (A) Tumor stage I. (B) Tumor stage I–III. (C) Black or African American. (D) White. (E) CR. (F) Age ≤60. (G) Age >60. (H) Weight ≤80 kg. (I) Weight >80 kg. (J) Height ≤160 cm. (K) Height >160 cm. (L) BMI ≤30. (M) BMI >30. (N) Histological type of endometrioid. (O) R0. (P) Without hormone therapy. (Q, R) With/without diabetes. (S, T) With/without radiation therapy. Abbreviations: UCEC: uterine corpus endometrial carcinoma; ZDHHC1: zinc finger DHHC-type containing 1; CR: complete response; BMI: body mass index; R0: residual tumor.
Figure 6
Figure 6
Prognostic nomogram based on ZDHHC1 expression and OS of patients with UCEC. Abbreviations: UCEC: uterine corpus endometrial carcinoma; ZDHHC1: zinc finger DHHC-type containing 1; OS: overall survival.
Figure 7
Figure 7
Visualization of ZDHHC1 co-expressed genes. (A) SPACA9. (B) SPATA18. (C) DRC3. (D) LRRC46. (E) TPPP3. (F) CNGA4. (G) ANKFN1. (H) RSPH1. Abbreviations: ZDHHC1: zinc finger DHHC-type containing 1; SPACA9: sperm acrosome associated 9; SPATA18: spermatogenesis associated 18; DRC3: dynein regulatory complex subunit 3; LRRC46: leucine rich repeat containing 46; TPPP3: tubulin polymerization promoting protein family member 3; CNGA4: cyclic nucleotide gated channel subunit alpha 4; ANKFN1: ankyrin repeat and fibronectin type III domain containing 1; RSPH1: radial spoke head component 1.
Figure 8
Figure 8
Functions and molecular pathways of ZDHHC1 co-expressed genes. (A–C) GO analysis. (D) Molecular pathways uncovered using KEGG analysis. Abbreviations: ZDHHC1: zinc finger DHHC-type containing 1; BP: biological process; KEGG: Kyoto Encyclopedia of Genes and Genomes; MF: molecular function; CC: cell component; GO: Gene Ontology.
Figure 9
Figure 9
A protein network of ZDHHC1 co-expressed genes.
Figure 10
Figure 10
ZDHHC1 overexpression prevents UCEC cell proliferation. (A–C) ZDHHC1 is overexpressed in UCEC cells. (D, E) Cell proliferation assessed with CCK-8 assay. Abbreviations: UCEC: uterine corpus endometrial carcinoma; ZDHHC1: zinc finger DHHC-type containing 1; CCK-8: Cell counting kit-8.
Figure 11
Figure 11
ZDHHC1 overexpression prevents UCEC cell proliferation. (A) Cell proliferation using EdU assay; (B, C) The ability of cell proliferation was analyzed statistically. Abbreviations: UCEC: uterine corpus endometrial carcinoma; ZDHHC1: zinc finger DHHC-type containing 1.
Figure 12
Figure 12
ZDHHC1 overexpression suppresses the cell cycle in UCEC. Abbreviations: UCEC: uterine corpus endometrial carcinoma; ZDHHC1: zinc finger DHHC-type containing 1.
Figure 13
Figure 13
ZDHHC1 overexpression hinders migration and invasion of UCEC cells. (A, B) Cell migration; (C, D) Cell invasion. Abbreviations: UCEC: uterine corpus endometrial carcinoma; ZDHHC1: zinc finger DHHC-type containing 1.
Figure 14
Figure 14
Correlation between ZDHHC1 overexpression and tumor-infiltrating immune cells. (A) NK CD56bright cells; (B) Eosinophils; (C) Th2 cells; (D) aDC; (E) NK cells; (F) iDC.
Figure 15
Figure 15
Correlation between ZDHHC1 overexpression and RNA modification genes. (A) IGF2BP1; (B) IGF2BP2; (C) FTO; (D) NOP56; (E) NOP58; (F) ALKBH5. Abbreviations: ZDHHC1, zinc finger DHHC-type containing 1; IGF2BP1/2, insulin like growth factor 2 mRNA binding protein 1/2; FTO, FTO alpha-ketoglutarate dependent dioxygenase; NOP56/58, NOP56/58 ribonucleoprotein; ALKBH5, ALKB homolog 5.
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References

    1. Pierce SR, Fang Z, Yin Y, West L, Asher M, Hao T, Zhang X, Tucker K, Staley A, Fan Y, Sun W, Moore DT, Xu C, et al.. Targeting dopamine receptor D2 as a novel therapeutic strategy in endometrial cancer. J Exp Clin Cancer Res. 2021; 40:61. 10.1186/s13046-021-01842-9 - DOI - PMC - PubMed
    1. Xu Q, Ge Q, Zhou Y, Yang B, Yang Q, Jiang S, Jiang R, Ai Z, Zhang Z, Teng Y. MELK promotes Endometrial carcinoma progression via activating mTOR signaling pathway. EBioMedicine. 2020; 51:102609. 10.1016/j.ebiom.2019.102609 - DOI - PMC - PubMed
    1. Zhang J, Zheng Z, Zheng J, Xie T, Tian Y, Li R, Wang B, Lin J, Xu A, Huang X, Yuan Y. Epigenetic-Mediated Downregulation of Zinc Finger Protein 671 (ZNF671) Predicts Poor Prognosis in Multiple Solid Tumors. Front Oncol. 2019; 9:342. 10.3389/fonc.2019.00342 - DOI - PMC - PubMed
    1. Yang B, Hu M, Fu Y, Sun D, Zheng W, Liao H, Zhang Z, Chen X. LASS2 mediates Nrf2-driven progestin resistance in endometrial cancer. Am J Transl Res. 2021; 13:1280–9. - PMC - PubMed
    1. Shen K, Yang L, Li FY, Zhang F, Ding LL, Yang J, Lu J, Wang NN, Wang Y. Research Progress of PARP Inhibitor Monotherapy and Combination Therapy for Endometrial Cancer. Curr Drug Targets. 2022; 23:145–55. 10.2174/1389450122666210617111304 - DOI - PubMed

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