Role of chromosome 1q copy number variation in hepatocellular carcinoma

Jacobs, Nathan R; Norton, Pamela A.

doi:10.4254/wjh.v13.i6.662

Cited by 1 publication

(2 citation statements)

References 63 publications

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“…We also found several significant alterations of molecular characteristics between HRisk and LRisk groups. Common somatic changes include mutations p53 and beta-catenin are frequently detected repeatedly in HCC, resulting in activation of the Wnt signaling pathway and dysregulation of the cell cycle, respectively ( Jacobs and Norton, 2021 ). TP53 is the most frequently mutated in HCC, and patients with TP53 mutations had a poorer prognosis compared with patients with wild-type TP53 ( Villanueva and Hoshida, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

“…Along with mutations, chromosomal abnormalities are frequent genetic events in HCC ( Schulze et al, 2016 ). In particular, broad genomic deletions have been noted for 1p, 4q, 6q, 8p, 13q, 16p, and 17q and gains for 1q, 6p, 8q, 17q, and 20q ( Jacobs and Norton, 2021 ). We found that HRisk had significantly higher copy number alterations than LRisk, suggesting that HRisk existed a deeper degree of chromosomal instability.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a DNA Damage Response and Repair-Related Gene-Pair Signature for Prognosis Stratification Analysis in Hepatocellular Carcinoma

et al. 2022

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Background: Nowadays, although the cause of hepatocellular carcinoma (HCC) mortality and recurrence remains at a high level, the 5-year survival rate is still very low. The DNA damage response and repair (DDR) pathway may affect HCC patients’ survival by influencing tumor development and therapeutic response. It is necessary to identify a prognostic DDR-related gene signature to predict the outcome of patients.Methods: Level 3 mRNA expression and clinical information were extracted from the TCGA website. The GSE14520 datasets, ICGC-LIRI datasets, and a Chinese HCC cohort were served as validation sets. Univariate Cox regression analysis and LASSO-penalized Cox regression analysis were performed to construct the DDR-related gene pair (DRGP) signature. Kaplan–Meier survival curves and time-dependent receiver operating characteristic (ROC) analysis curves were calculated to determine the predictive ability of this prognostic model. Then, a prognostic nomogram was established to help clinical management. We investigated the difference in biological processes between HRisk and LRisk by conducting several enrichment analyses. The TIDE algorithm and R package “pRRophetic” were applied to estimate the immunotherapeutic and chemotherapeutic response.Results: We constructed the prognostic signature based on 23 DDR-related gene pairs. The patients in the training datasets were divided into HRisk and LRisk groups at median cut-off. The HRisk group had significantly poorer OS than the LRisk group, and the signature was an independent prognostic indicator in HCC. Furthermore, a nomogram of the riskscore combined with TNM stage was constructed and detected by the calibration curve and decision curve. The LRisk group was associated with higher expression of HBV oncoproteins and metabolism pathways, while DDR-relevant pathways and cell cycle process were enriched in the HRisk group. Moreover, patients in the LRisk group may be more beneficial from immunotherapy. We also found that TP53 gene was more frequently mutated in the HRisk group. As for chemotherapeutic drugs commonly used in HCC, the HRisk group was highly sensitive to 5-fluorouracil, while the LRisk group presented with a significantly higher response to gefitinib and gemcitabine.Conclusion: Overall, we developed a novel DDR-related gene pair signature and nomogram to assist in predicting survival outcomes and clinical treatment of HCC patients. It also helps understand the underlying mechanisms of different DDR patterns in HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%