Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb 18;22(1):186.
doi: 10.1186/s12885-022-09279-9.

The genetic landscape of pancreatic head ductal adenocarcinoma in China and prognosis stratification

Yefan Yang #  1 , Ying Ding #  1 , Yuxi Gong  1 , Sha Zhao  1 , Mingna Li  1 , Xiao Li  1 , Guoxin Song  1 , Boya Zhai  1 , Jin Liu  2 , Yang Shao  3 , Liuqing Zhu  3 , Jiaohui Pang  3 , Yutong Ma  3 , Qiuxiang Ou  3 , Xue Wu  3 , Zhihong Zhang  4
Affiliations

The genetic landscape of pancreatic head ductal adenocarcinoma in China and prognosis stratification

Yefan Yang et al. BMC Cancer. .

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is the major subtype of pancreatic cancer and head PDACs show distinct characteristics from body/tail PDACs. With limited studies based on Asian population, the mutational landscape of Asian PDAC remains unclear.

Methods: One hundred fifty-one Chinese patients with head PDAC were selected and underwent targeted 425-gene sequencing. Genomic alterations, tumor mutational burden, and microsatellite instability were analyzed and compared with a TCGA cohort.

Results: The genomic landscape of Chinese and Western head PDAC had identical frequently-mutated genes including KRAS, TP53, SMAD4, and CDKN2A. KRAS hotspot in both cohorts was codon 12 but Chinese PDACs containing more G12V but fewer G12R variants. Potentially pathogenic fusions, CHD2-BRAF and KANK1-MET were identified in two KRAS wild-type patients. Serum cancer antigens CA125 and CA19-9 were positively associated with SMAD4 alterations while high CEA was enriched in wild-type CDKN2A subgroup. The probability of vascular invasion was lower in patients with RNF43 alterations. The nomogram developed including histology grade, the mutation status of SMAD4, TGFBR2, and PREX2 could calculate the risk score of prognoses validated by Chinese and TCGA cohort.

Conclusions: Chinese head PDAC contained more KRAS G12V mutation than Western population. The well-performed nomogram may improve post-operation care in real-world practice.

Keywords: Genomic landscape; NGS; Pancreatic cancer; Prognosis prediction.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Concurrent mutations in Chinese cohort and incidence comparison with TCGA cohort. A The oncoprint of all patients in the Chinese head PDAC cohort. The top panel includes the most frequently mutated genes. The genes in the middle and the bottom panel are DNA damage repair pathway related and other oncogenic genes, respectively. The alteration frequency of each gene is labled on the left side. B The alteration frequency comparison between the cohort in this study and the TCGA cohort with a coloured scale. The P-value less than 0.05 is statistically significant and highlighted in red. C A bar plot shows the proportion of each KRAS alteration subtype in this study and the TCGA cohort
Fig. 2
Fig. 2
Nomogram for risk score calculation and its performance validation. A The nomogram calculating the risk score of one-year mortality probability based on the selected four features. The status of each feature corresponds to the score on the top panel. The risk score is the sum of the scores corresponding to each feature which then represents the one-year mortality probability according to the scale bars. The risk score of 15 is the cutoff of the high and low risk groups. The overall survival (OS) curves of patients with high (> 15, red) and low (≤ 15, blue) in the Chinese training cohort (B), Chinese validation cohort (C), and the TCGA cohort (D) are shown. Median OS (MOS), HR (95% CI), and P-value are labeled on the right-up corner of each figure
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30. - PubMed
    1. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–132. - PubMed
    1. Haeberle L, Esposito I. Pathology of pancreatic cancer. Transl Gastroenterol Hepatol. 2019;4:50. - PMC - PubMed
    1. Slack JM. Developmental biology of the pancreas. Development. 1995;121:1569–1580. - PubMed
    1. Artinyan A, Soriano PA, Prendergast C, Low T, Ellenhorn JD, Kim J. The anatomic location of pancreatic cancer is a prognostic factor for survival. HPB (Oxford) 2008;10:371–376. - PMC - PubMed

MeSH terms