Evidence map›Paper›PMID 40145314›Full record

ArticleCancer medicine2025

Decoding Genomic Diversity to Guide Tumor Lesion-Specific Treatment of Multifocal Hepatocellular Carcinoma.

Kenji Amemiya, Yosuke Hirotsu, Yuji Iimuro, Ryosuke Tajiri, Toshio Oyama, Shuntaro Obi, Hitoshi Mochizuki, Masao Omata

Abstract read
In one paragraph

Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Kenji AmemiyaGenome Analysis Center, Yamanashi Central Hospital, Kofu, Yamanashi, Japan.ORCID https://orcid.org/0000-0003-4223-0528
Yosuke HirotsuGenome Analysis Center, Yamanashi Central Hospital, Kofu, Yamanashi, Japan.ORCID https://orcid.org/0000-0002-8002-834X
Yuji IimuroDepartment of Surgery, Yamanashi Central Hospital, Kofu, Yamanashi, Japan.
Ryosuke TajiriDepartment of Pathology, Yamanashi Central Hospital, Kofu, Yamanashi, Japan.
Toshio OyamaDepartment of Pathology, Yamanashi Central Hospital, Kofu, Yamanashi, Japan.
Shuntaro ObiDepartment of Gastroenterology, Yamanashi Central Hospital, Kofu, Yamanashi, Japan.
Hitoshi MochizukiGenome Analysis Center, Yamanashi Central Hospital, Kofu, Yamanashi, Japan.
Masao OmataDepartment of Gastroenterology, Yamanashi Central Hospital, Kofu, Yamanashi, Japan.

Funding

Grant-in-Aid for Scientific Research (B) 20H03668Grant-in-Aid for Scientific Research (B) 23H02955Grant-in-Aid for the Genome Research Project from Yamanashi PrefectureJapan Society for the Promotion of Science (JSPS) KAKENHI Early-Career Scientists JP18K16292Japan Society for the Promotion of Science (JSPS) KAKENHI Early-Career Scientists JP23K14497Kato Memorial Bioscience FoundationResearch Grant for Young ScholarsTakeda Science FoundationUehara Memorial FoundationYASUDA Medical Foundation
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is a primary liver cancer often associated with chronic liver disease and characterized by multifocal tumor lesions with synchronous and metachronous lesions, which poses treatment challenges due to potential genomic heterogeneity. This study aims to assess the consistency of actionable mutation profiles across synchronous and metachronous lesions in HCC patients.

methodsThis study analyzed 68 patients with multifocal HCC, including 193 tumor lesions (82 synchronous, 111 metachronous). Genomic profiling of 72 HCC-related genes was performed using next-generation sequencing. We collected clinical and pathological data, including tumor size, grade, fibrosis, and etiology. Patients were categorized into two groups based on the consistency of actionable mutations among multifocal HCC. Statistical analyses compared clinicopathological features between these groups.

resultsA total of 252 and 445 somatic mutations were identified in synchronous and metachronous tumors, respectively. Synchronous tumors had an average of 3.1 somatic mutations and 0.7 actionable mutations per lesion. Metachronous tumors had 4.0 somatic mutations and 1.0 actionable mutations per lesion. Actionable variants were found in 12 (36.4%) of 33 patients and 20 (24.4%) of 82 nodules in the synchronous tumors, and 23 (65.7%) of 35 patients and 42 (37.8%) of 111 nodules in the metachronous tumors. Compared to synchronous tumors, metachronous tumors exhibited significantly aberrant signaling pathways including the Wnt/β-catenin (p = 0.009) and KEAP1/NRF2 (p = 0.022) pathways. There was no correlation with significant clinical differences in tumor characteristics between the consistent and divergent actionable mutation groups. Notably, divergent actionable mutations were identified in 45.6% of patients, which may be beneficial for changing potential therapies for individual tumors.

conclusionThe study shows substantial inter-tumoral heterogeneity in multifocal HCC, indicating the necessity for comprehensive molecular profiling for tailored treatment strategies. Divergent actionable mutations across lesions suggest that a uniform treatment approach may not be effective in some patients with multifocal HCC.

Indexed as

Biomarkers, TumorCarcinoma, HepatocellularLiver NeoplasmsNeoplasms, Multiple PrimaryNeoplasms, Second PrimaryAdultAgedFemaleGenomicsHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedMutationBiomarkers, Tumorgenomic diversitymultifocal HCCsNGSprecision medicine

Identifiers

PMID40145314
PMCPMC11947740

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.