Prediction of Adrenocortical Carcinoma Relapse and Prognosis with a Set of Novel Multigene Panels

Lin, Xiaozeng; Gu, Yan; Su, Yingying; Dong, Ying; Major, Pierre; Kapoor, Anil; Tang, Damu

doi:10.3390/cancers14112805

Cited by 4 publications

(2 citation statements)

References 98 publications

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“…There are a limited number of reports on ACC prognostic biomarkers. Previous studies tried to construct a microarray‐based prognostic predictor and identified genes pair BUB1B and PINK1 as optimal predictors (AUC = 0.83) of poor prognosis in ACC [ 24 , 25 ]. To evaluate the predictive ability of overall status using these 15 genera, we performed area under curve (AUC) receiver operator characteristic (ROC) analysis.…”

Section: Resultsmentioning

confidence: 99%

EXPRESSION OF CONCERN: Intratumoral microbiota is associated with prognosis in patients with adrenocortical carcinoma

Zhang

Wang

et al. 2023

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Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy. Recent studies have discovered a pivotal role of the intratumoral microbiota in various cancers, yet it remains elusive in ACC. Here, we explored the intratumoral microbiome data derived from in silico identification, further validated in an in‐house cohort by bacterial 16S rRNA fluorescence in situ hybridization and lipopolysaccharide staining. Unsupervised clustering determined two naturally distinct clusters of the intratumoral microbiome in ACC, which was associated with overall survival. The incorporation of microbial signatures enhanced the prognostic performance of the clinical stage in an immunity‐dependent manner. Genetic and transcriptomic association analyses identified significant upregulation of the cell cycle and p53 signaling pathways associated with microbial signatures for worsened prognosis. Our study not only supports the presence of intratumoral bacteria but also implies a prognostic and biological role of intratumoral microbiota in ACC, which can advance a better understanding of the biology of ACC.

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Section: Resultsmentioning

confidence: 99%

EXPRESSION OF CONCERN: Intratumoral microbiota is associated with prognosis in patients with adrenocortical carcinoma

Zhang

Wang

et al. 2023

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“…We analyzed Overlap36’s potential in stratification of poor OS of SKCM. We first matched 34 of the 36 murine genes to the human SKCM PanCancer Atlas dataset (for simplicity, these 34 genes are referred to as Overlap36) and merged them into a megagene (Overlap36 risk score) using coefficients generated by multivariate Cox analysis following our system [ 85 , 86 ] as described in Fig. 1 .…”

Section: Resultsmentioning

confidence: 99%

PCSK9 facilitates melanoma pathogenesis via a network regulating tumor immunity

Lin

Dong

et al. 2023

J Exp Clin Cancer Res

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Background PCSK9 regulates cholesterol homeostasis and promotes tumorigenesis. However, the relevance of these two actions and the mechanisms underlying PCSK9’s oncogenic roles in melanoma and other cancers remain unclear. Methods PCSK9’s association with melanoma was analysed using the TCGA dataset. Empty vector (EV), PCSK9, gain-of-function (D374Y), and loss-of-function (Q152H) PCSK9 mutant were stably-expressed in murine melanoma B16 cells and studied for impact on B16 cell-derived oncogenesis in vitro and in vivo using syngeneic C57BL/6 and Pcsk9−/− mice. Intratumoral accumulation of cholesterol was determined. RNA-seq was performed on individual tumor types. Differentially-expressed genes (DEGs) were derived from the comparisons of B16 PCSK9, B16 D374Y, or B16 Q152H tumors to B16 EV allografts and analysed for pathway alterations. Results PCSK9 expression and its network negatively correlated with the survival probability of patients with melanoma. PCSK9 promoted B16 cell proliferation, migration, and growth in soft agar in vitro, formation of tumors in C57BL/6 mice in vivo, and accumulation of intratumoral cholesterol in a manner reflecting its regulation of the low-density lipoprotein receptor (LDLR): Q152H, EV, PCSK9, and D374Y. Tumor-associated T cells, CD8 + T cells, and NK cells were significantly increased in D374Y tumors along with upregulations of multiple immune checkpoints, IFNγ, and 143 genes associated with T cell dysfunction. Overlap of 36 genes between the D374Y DEGs and the PCSK9 DEGs predicted poor prognosis of melanoma and resistance to immune checkpoint blockade (ICB) therapy. CYTH4, DENND1C, AOAH, TBC1D10C, EPSTI1, GIMAP7, and FASL (FAS ligand) were novel predictors of ICB therapy and displayed high level of correlations with multiple immune checkpoints in melanoma and across 30 human cancers. We observed FAS ligand being among the most robust biomarkers of ICB treatment and constructed two novel and effective multigene panels predicting response to ICB therapy. The profiles of allografts produced by B16 EV, PCSK9, D374Y, and Q152H remained comparable in C57BL/6 and Pcsk9−/− mice. Conclusions Tumor-derived PCSK9 plays a critical role in melanoma pathogenesis. PCSK9’s oncogenic actions are associated with intratumoral cholesterol accumulation. PCSK9 systemically affects the immune system, contributing to melanoma immune evasion. Novel biomarkers derived from the PCSK9-network effectively predicted ICB therapy responses.

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Comprehensive analysis of a tryptophan metabolism-related model in the prognostic prediction and immune status for clear cell renal carcinoma

Yao,

Zhang,

Wang

et al. 2024

Eur J Med Res

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Background Clear cell renal cell carcinoma (ccRCC) is characterized as one of the most common types of urological cancer with high degrees of malignancy and mortality. Due to the limited effectiveness of existing traditional therapeutic methods and poor prognosis, the treatment and therapy of advanced ccRCC patients remain challenging. Tryptophan metabolism has been widely investigated because it significantly participates in the malignant traits of multiple cancers. The functions and prognostic values of tryptophan metabolism-related genes (TMR) in ccRCC remain virtually obscure. Methods We employed the expression levels of 40 TMR genes to identify the subtypes of ccRCC and explored the clinical characteristics, prognosis, immune features, and immunotherapy response in the subtypes. Then, a model was constructed for the prediction of prognosis based on the differentially expressed genes (DEGs) in the subtypes from the TCGA database and verified using the ICGC database. The prediction performance of this model was confirmed by the receiver operating characteristic (ROC) curves. The relationship of Risk Score with the infiltration of distinct tumor microenvironment cells, the expression profiles of immune checkpoint genes, and the treatment benefits of immunotherapy and chemotherapy drugs were also investigated. Results The two subtypes revealed dramatic differences in terms of clinical characteristics, prognosis, immune features, and immunotherapy response. The constructed 6-gene-based model showed that the high Risk Score was significantly connected to poor overall survival (OS) and advanced tumor stages. Furthermore, increased expression of CYP1B1, KMO, and TDO2 was observed in ccRCC tissues at the translation levels, and an unfavorable prognosis for these patients was also found. Conclusion We identified 2 molecular subtypes of ccRCC based on the expression of TMR genes and constructed a prognosis-related model that may be used as a powerful tool to guide the prediction of ccRCC prognosis and personalized therapy. In addition, CYP1B1, KMO, and TDO2 can be regarded as the risk prognostic genes for ccRCC.

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Prediction of Adrenocortical Carcinoma Relapse and Prognosis with a Set of Novel Multigene Panels

Cited by 4 publications

References 98 publications

EXPRESSION OF CONCERN: Intratumoral microbiota is associated with prognosis in patients with adrenocortical carcinoma

EXPRESSION OF CONCERN: Intratumoral microbiota is associated with prognosis in patients with adrenocortical carcinoma

PCSK9 facilitates melanoma pathogenesis via a network regulating tumor immunity

Comprehensive analysis of a tryptophan metabolism-related model in the prognostic prediction and immune status for clear cell renal carcinoma

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