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Multi-omics characterization reveals the pathogenesis of liver focal nodular hyperplasia.

ABSTRACT: The molecular landscape and pathogenesis of focal nodular hyperplasia (FNH) have yet to be elucidated. We performed multi-omics approaches on FNH and paired normal liver tissues from 22 patients, followed by multi-level bioinformatic analyses and experimental validations. Generally, FNH had low mutation burden with low variant allele frequencies, and the mutation frequency significantly correlated with proliferation rate. Although no recurrently deleterious genomic events were found, some putative tumor suppressors or oncogenes were involved. Mutational signatures indicated potential impaired mismatch function and possible poison contact. Integrated analyses unveiled a group of FNH specific endothelial cells that uniquely expressed SOST and probably had strong interaction with fibroblasts through PDGFB/PDGFRB pathway to promote fibrosis. Notably, in one atypical FNH (patient No.11) with pronounced copy number variations, we observed a unique immune module. Most FNH are benign, but molecularly atypical FNH still exist; endothelial cell derived PDGFB probably promotes the fibrogenic process in FNH.

SUBMITTER: Liu Y

PROVIDER: S-EPMC9436768 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Multi-omics characterization reveals the pathogenesis of liver focal nodular hyperplasia.

Liu Yuming Y Zhang Jinmai J Wang Zhuo Z Ma Jiaqiang J Wang Ke K Rao Dongning D Zhang Mao M Lin Youpei Y Wu Yingcheng Y Yang Zijian Z Dong Liangqing L Ding Zhenbin Z Zhang Xiaoming X Fan Jia J Shi Yongyong Y Gao Qiang Q

iScience 20220811 9

The molecular landscape and pathogenesis of focal nodular hyperplasia (FNH) have yet to be elucidated. We performed multi-omics approaches on FNH and paired normal liver tissues from 22 patients, followed by multi-level bioinformatic analyses and experimental validations. Generally, FNH had low mutation burden with low variant allele frequencies, and the mutation frequency significantly correlated with proliferation rate. Although no recurrently deleterious genomic events were found, some putati ...[more]

PMID: 36060063

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Project description:ObjectivesNewly detected hepatic nodules during follow-up of cancer survivors receiving chemotherapy may pose a diagnostic dilemma. We investigated a series of hepatic focal nodular hyperplasia (FNH) diagnosed by either typical MRI features and follow-up or pathology in cancer survivors.MethodsThis retrospective study evaluated 38 patients with tumours who developed new hepatic FNH after cyclophosphamide-based (n = 19) and oxaliplatin-based (n = 19) chemotherapies. The main tumour types were breast cancer (n = 18) and colorectal cancer (n = 17). MRI findings, clinical features, and temporal evolution of all target hepatic lesions (n = 63) were reported. In addition, the two chemotherapy drug groups were compared.ResultsThe median interval between chemotherapy completion and FNH detection was 30.4 months (12.9, 49.4). Six patients underwent biopsy or surgery, while the remaining patients were diagnosed based on typical MRI features and long-term follow-up. Among the patients, 60.5% (23/38) presented with multiple nodules and 63 target lesions were detected. The median size of target lesions was 11.5 mm (8.4, 15.1). The median follow-up time was 32.5 months (21.2, 48.6), and 15 patients experienced changes in their lesions during the follow-up period (11 increased and 4 decreased). The cyclophosphamide-based treatment group had a younger population, a greater proportion of females, and a shorter time to discovery than the oxaliplatin-based chemotherapy group (all p ≤ 0.016).ConclusionsFNH may occur in cancer survivors after cyclophosphamide- or oxaliplatin-based chemotherapy. Considering a patient's treatment history and typical MRI findings can help avoid misdiagnosis and unnecessary invasive treatment.Clinical relevance statementWhen cancer survivors develop new hepatic nodules during follow-up, clinicians should think of the possibility of focal nodular hyperplasia in addition to liver metastasis, especially if the cancer survivors were previously treated with cyclophosphamide or oxaliplatin.Key pointsCancer survivors, after chemotherapy, can develop hepatic focal nodular hyperplasia. Cyclophosphamide and oxaliplatin are two chemotherapeutic agents that predispose to focal nodular hyperplasia development. Focal nodular hyperplasia occurs at shorter intervals in patients treated with cyclophosphamide.

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Multi-omics characterization reveals the pathogenesis of liver focal nodular hyperplasia.

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Multi-omics characterization reveals the pathogenesis of liver focal nodular hyperplasia.

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