Genomic profile of pancreatic tumor in the coastal regions of Eastern China: A multicenter analysis of 40 cases

Jing WANG; Bin TAN; Zhijie ZHAO; Haochen ZHONG; Linlin QU

doi:10.3969/j.issn.1001-5256.2022.02.028

Volume 38 Issue 2

Feb. 2022

Turn off MathJax

Article Contents

Abstract

References

Supplements

Article Navigation > Journal of Clinical Hepatology > 2022 > 38(2): 409-414

PDF( 3577 KB)

Genomic profile of pancreatic tumor in the coastal regions of Eastern China: A multicenter analysis of 40 cases

DOI: 10.3969/j.issn.1001-5256.2022.02.028

Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China

Research funding:

Scientific Research Award Fund for Young and Middle-Aged Scientists in Shandong Province (BS2011YY004);

Chen Xiaoping Science and Technology Development Fund of Hubei Province (CXPJJH12000002-2020057);

Li Jieshou Intestinal Barrier Research Foundation of China International Medical Exchange Foundation in 2019 (Z-2017-24-2009)

More Information

Corresponding author: QU Linlin, taxue9455@sina.com
Received Date: 2021-07-07
Accepted Date: 2021-08-26
Published Date: 2022-02-20

Abstract

Abstract

Objective To investigate the gene mutations of Chinese patients with pancreatic cancer in the coastal regions of Eastern China, and to provide a basis for individualized treatment. Methods A total of 40 patients who were admitted and diagnosed with malignant pancreatic tumor after surgical treatment in The Affiliated Hospital of Qingdao University, Qingdao Municipal Hospital, Yantaishan Hospital, and Yantai Sino-France Friendship Hospital from January 2017 to June 2019 were enrolled. Next-generation sequencing (NGS) was used to detect gene mutations in tumor tissue and somatic cells, and the map of gene mutations was plotted to analyze genomic alterations. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison between groups. Results Among the 40 patients, 34 (85.0%) had pancreatic ductal adenocarcinoma, 3 (7.5%) had solid pseudopapillary neoplasm of the pancreas, 1 (2.5%) had pancreatic neuroendocrine tumor, and 2 (5.0%) had unclear typing. KRAS (80.0%, 32/40), TP53 (70.0%, 28/40), CDKN2A (32.5%, 13/40), SMAD4 (17.5%, 7/40), and AKT2 (17.5%, 7/40) were the most common mutations, and there was no significant difference in survival time between the patients with these five common gene mutations (all P > 0.05). Conclusion NGS technology can provide comprehensive and accurate information of genomic alterations and may provide novel potential biomarkers for the diagnosis and precise treatment of pancreatic cancer. The analysis of mutant genes also lays a foundation for the individualized treatment of pancreatic cancer.
- Pancreatic Neoplasms,
- Genome,
- Mutation

FullText(HTML)

References(28)

References

[1]	SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69(1): 7-34. DOI: 10.3322/caac.21551.
[2]	STEUER CE, RAMALINGAM SS. Tumor mutation burden: Leading immunotherapy to the era of precision medicine?[J]. J Clin Oncol, 2018, 36(7): 631-632. DOI: 10.1200/JCO.2017.76.8770.
[3]	von HOFF DD, ERVIN T, ARENA FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine[J]. N Engl J Med, 2013, 369(18): 1691-1703. DOI: 10.1056/NEJMoa1304369.
[4]	CONROY T, PAILLOT B, FRANÇOIS E, et al. Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer—a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study[J]. J Clin Oncol, 2005, 23(6): 1228-1236. DOI: 10.1200/JCO.2005.06.050.
[5]	FRANCO J, WITKIEWICZ AK, KNUDSEN ES. CDK4/6 inhibitors have potent activity in combination with pathway selective therapeutic agents in models of pancreatic cancer[J]. Oncotarget, 2014, 5(15): 6512-6525. DOI: 10.18632/oncotarget.2270.
[6]	OSHIMA M, OKANO K, MURAKI S, et al. Immunohistochemically detected expression of 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4) strongly predicts survival in patients with resectable pancreatic cancer[J]. Ann Surg, 2013, 258(2): 336-346. DOI: 10.1097/SLA.0b013e3182827a65.
[7]	BIANKIN AV, WADDELL N, KASSAHN KS, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes[J]. Nature, 2012, 491(7424): 399-405. DOI: 10.1038/nature11547.
[8]	KAWAGUCHI K, IGARASHI K, MIYAKE K, et al. MEK inhibitor trametinib in combination with gemcitabine regresses a patient-derived orthotopic xenograft (PDOX) pancreatic cancer nude mouse model[J]. Tissue Cell, 2018, 52: 124-128. DOI: 10.1016/j.tice.2018.05.003.
[9]	BOURNET B, BUSCAIL C, MUSCARI F, et al. Targeting KRAS for diagnosis, prognosis, and treatment of pancreatic cancer: Hopes and realities[J]. Eur J Cancer, 2016, 54: 75-83. DOI: 10.1016/j.ejca.2015.11.012.
[10]	MORTON JP, TIMPSON P, KARIM SA, et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer[J]. Proc Natl Acad Sci U S A, 2010, 107(1): 246-251. DOI: 10.1073/pnas.0908428107.
[11]	Cancer Genome Atlas Research Network. Integrated genomic characterization of pancreatic ductal adenocarcinoma[J]. Cancer Cell, 2017, 32(2): 185-203. DOI: 10.1016/j.ccell.2017.07.007.
[12]	WADDELL N, PAJIC M, PATCH AM, et al. Whole genomes redefine the mutational landscape of pancreatic cancer[J]. Nature, 2015, 518(7540): 495-501. DOI: 10.1038/nature14169.
[13]	ORMANNS S, HAAS M, REMOLD A, et al. The impact of SMAD4 loss on outcome in patients with advanced pancreatic cancer treated with systemic chemotherapy[J]. Int J Mol Sci, 2017, 18(5): 1094. DOI: 10.3390/ijms18051094.
[14]	XIA X, WU W, HUANG C, et al. SMAD4 and its role in pancreatic cancer[J]. Tumour Biol, 2015, 36(1): 111-119. DOI: 10.1007/s13277-014-2883-z.
[15]	CRANE CH, VARADHACHARY GR, YORDY JS, et al. Phase Ⅱ trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: Correlation of Smad4(Dpc4) immunostaining with pattern of disease progression[J]. J Clin Oncol, 2011, 29(22): 3037-3043. DOI: 10.1200/JCO.2010.33.8038.
[16]	OTTENHOF NA, MORSINK FH, TEN KATE F, et al. Multivariate analysis of immunohistochemical evaluation of protein expression in pancreatic ductal adenocarcinoma reveals prognostic significance for persistent Smad4 expression only[J]. Cell Oncol (Dordr), 2012, 35(2): 119-126. DOI: 10.1007/s13402-012-0072-x.
[17]	SHIN SH, KIM HJ, HWANG DW, et al. The DPC4/SMAD4 genetic status determines recurrence patterns and treatment outcomes in resected pancreatic ductal adenocarcinoma: A prospective cohort study[J]. Oncotarget, 2017, 8(11): 17945-17959. DOI: 10.18632/oncotarget.14901.
[18]	CHENG JQ, RUGGERI B, KLEIN WM, et al. Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA[J]. Proc Natl Acad Sci U S A, 1996, 93(8): 3636-3641. DOI: 10.1073/pnas.93.8.3636.
[19]	RUGGERI BA, HUANG L, WOOD M, et al. Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas[J]. Mol Carcinog, 1998, 21(2): 81-86.
[20]	CUI Y, WANG Q, WANG J, et al. Knockdown of AKT2 expression by RNA interference inhibits proliferation, enhances apoptosis, and increases chemosensitivity to the anticancer drug VM-26 in U87 glioma cells[J]. Brain Res, 2012, 1469: 1-9. DOI: 10.1016/j.brainres.2012.06.043.
[21]	NITULESCU GM, MARGINA D, JUZENAS P, et al. Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review)[J]. Int J Oncol, 2016, 48(3): 869-885. DOI: 10.3892/ijo.2015.3306.
[22]	CHEN D, NIU M, JIAO X, et al. Inhibition of AKT2 enhances sensitivity to gemcitabine via regulating PUMA and NF-κB signaling pathway in human pancreatic ductal adenocarcinoma[J]. Int J Mol Sci, 2012, 13(1): 1186-1208. DOI: 10.3390/ijms13011186.
[23]	LIU Q, TURNER KM, ALFRED YUNG WK, et al. Role of AKT signaling in DNA repair and clinical response to cancer therapy[J]. Neuro Oncol, 2014, 16(10): 1313-1323. DOI: 10.1093/neuonc/nou058.
[24]	KORINEK V, BARKER N, MORIN PJ, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC^-/- colon carcinoma[J]. Science, 1997, 275(5307): 1784-1787. DOI: 10.1126/science.275.5307.1784.
[25]	LOGAN CY, NUSSE R. The Wnt signaling pathway in development and disease[J]. Annu Rev Cell Dev Biol, 2004, 20: 781-810. DOI: 10.1146/annurev.cellbio.20.010403.113126.
[26]	CLEVERS H. Wnt/beta-catenin signaling in development and disease[J]. Cell, 2006, 127(3): 469-480. DOI: 10.1016/j.cell.2006.10.018.
[27]	SINGHI AD, GEORGE B, GREENBOWE JR, et al. Real-time targeted genome profile analysis of pancreatic ductal adenocarcinomas identifies genetic alterations that might be targeted with existing drugs or used as biomarkers[J]. Gastroenterology, 2019, 156(8): 2242-2253. DOI: 10.1053/j.gastro.2019.02.037.
[28]	WEISS GJ, BLAYDORN L, BECK J, et al. Phase Ib/Ⅱ study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma[J]. Invest New Drugs, 2018, 36(1): 96-102. DOI: 10.1007/s10637-017-0525-1.

Relative Articles

[1]	Jialuo WANG, Yufeng ZHENG, Qingfang XIONG, Yongfeng YANG. Etiology spectrum， clinical features， and gene mutations of unexplained intrahepatic cholestasis： An analysis of 62 cases[J]. Journal of Clinical Hepatology, 2025, 41(2): 307-313. doi: 10.12449/JCH250217
[2]	Xiaoyao LI, Jianfeng DUAN, Dacheng WANG, Xiancheng CHEN, Beiyuan ZHANG, Wenkui YU. Recurrent hypertriglyceridemic acute pancreatitis in an adult patient caused by the de novo mutation of p.K327N in the GPD1 gene： A case report[J]. Journal of Clinical Hepatology, 2024, 40(2): 361-364. doi: 10.12449/JCH240222
[3]	Sa LYU, Bing ZHU, Tianjiao XU, Shaoli YOU. The extreme reduction in cholinesterase caused by compound heterozygous mutations in the BCHE gene： A case report[J]. Journal of Clinical Hepatology, 2024, 40(10): 2075-2078. doi: 10.12449/JCH241023
[4]	Shuduo WU, Yibo ZHAN, Xinhua LI, Changlei XU, Minling CAO, Xiaoling CHI. Hereditary hemochromatosis with multiple organ damage caused by HJV gene mutation in adults: A case report[J]. Journal of Clinical Hepatology, 2022, 38(11): 2571-2574. doi: 10.3969/j.issn.1001-5256.2022.11.026
[5]	Dan YANG, Cuiwei ZHANG, Mingming DENG. A compound heterozygous mutation in the ATP7B gene with acute fatty liver of pregnancy: A case report[J]. Journal of Clinical Hepatology, 2022, 38(1): 167-169. doi: 10.3969/j.issn.1001-5256.2022.01.027
[6]	Bo YI, Xue LI, Shanhong TANG. Research advances in the mechanism of abnormal bile acid metabolism caused by gene mutation[J]. Journal of Clinical Hepatology, 2022, 38(9): 2136-2140. doi: 10.3969/j.issn.1001-5256.2022.09.036
[7]	Lei HUA, Quan SUN, Wenbin XU, Long ZHANG, Gongqiang WANG. ABCB4 gene mutation-associated liver cirrhosis misdiagnosed as Wilson's disease: A case report[J]. Journal of Clinical Hepatology, 2021, 37(6): 1419-1420. doi: 10.3969/j.issn.1001-5256.2021.06.039
[8]	Chengyu ZHU, Qi CHEN, Zhongxin FENG. Hereditary hemochromatosis caused by mutation in the SLC40A1 gene: A case report[J]. Journal of Clinical Hepatology, 2021, 37(5): 1180-1182. doi: 10.3969/j.issn.1001-5256.2021.05.041
[9]	Yuhang WENG, Yongfeng YANG. Association between genotype and phenotype of ABCB4 gene mutation[J]. Journal of Clinical Hepatology, 2021, 37(11): 2723-2726. doi: 10.3969/j.issn.1001-5256.2021.11.052
[10]	Yong ZHANG, Zhengfa MAO. Association of tuberous sclerosis gene 1/2 mutations with the progression of hepatocellular carcinoma and prognosis[J]. Journal of Clinical Hepatology, 2021, 37(1): 84-88. doi: 10.3969/j.issn.1001-5256.2021.01.017
[11]	Yang Fan, Wang YiRou, Yu XiaoDan, Ma Xiong, Wang XiuMin. Congenital hepatic fibrosis with retinitis pigmentosa caused by mutations of the TMEM67 gene and CNGB1 gene: A case report[J]. Journal of Clinical Hepatology, 2020, 36(7): 1593-1595. doi: 10.3969/j.issn.1001-5256.2020.07.029
[12]	Liang Chen, Bai Li, Zheng SuJun. Research advances in mutation characteristics of the UGT1A1 gene in Gilbert syndrome and its influence on intrahepatic and extrahepatic systems[J]. Journal of Clinical Hepatology, 2019, 35(7): 1632-1635. doi: 10.3969/j.issn.1001-5256.2019.07.046
[13]	Li Ning, Zhang Xin, Li Rui, Jiao Lin. Hepatolenticular degeneration with MTHFR gene mutation: A case report[J]. Journal of Clinical Hepatology, 2019, 35(11): 2549-2550. doi: 10.3969/j.issn.1001-5256.2019.11.033
[14]	Zhou HuaBang, Hu HePing. Challenges in precise treatment for primary liver cancer based on gene mutation[J]. Journal of Clinical Hepatology, 2017, 33(7): 1209-1210. doi: 10.3969/j.issn.1001-5256.2017.07.001
[15]	Pang Ting, Xing HuiChun. Correlation between drug-resistance gene mutations and hepatocellular carcinoma in patients with hepatitis B virus infection[J]. Journal of Clinical Hepatology, 2017, 33(1): 82-86. doi: 10.3969/j.issn.1001-5256.2017.01.017
[16]	Lu: TingXia, Zhang Wei, Li XiaoJin, Xu AnJian, Zhao XinYan, Ou XiaoJuan, Huang Jian. Characteristics of gene mutation in Chinese patients with hereditary hemochromatosis[J]. Journal of Clinical Hepatology, 2016, 32(8): 1571-1574. doi: 10.3969/j.issn.1001-5256.2016.08.028
[17]	Hu AiRong, Hu Ting. Common mutations of hepatitis B virus and their clinical significance[J]. Journal of Clinical Hepatology, 2016, 32(8): 1463-1467. doi: 10.3969/j.issn.1001-5256.2016.08.006
[18]	Mao WeiWu, Du Peng, Zhang WenJie, Li Jing, Qu Yan, Shi HuaiYuan, Wang YanXia. Impact of HCV 5′NCR genetic mutation on standard program of anti-HCV therapy[J]. Journal of Clinical Hepatology, 2015, 31(4): 585-587. doi: 10.3969/j.issn.1001-5256.2015.04.026
[19]	Guo HongMei, Zheng BiXia, Li Mei. Neonatal intrahepatic cholestasis caused by citrin deficiency due to SLC25A13 gene mutations: a clinical analysis of 21cases in Nanjing, China[J]. Journal of Clinical Hepatology, 2014, 30(11): 1127-1131. doi: 10.3969/j.issn.1001-5256.2014.11.008

Supplements(1)

Supplements

王晶-华东沿海地区多中心40例胰腺肿瘤患者基因组图谱分析-附录1.pdf

Cited By

Cited by
Periodical cited type(1)
1. 王淼东，彭佩纯，陈泽山，邓鑫. 基于生物信息学研究肝癌脂肪酸代谢lncRNA预后免疫反应及药物敏感性分析. 中国免疫学杂志. 2024(12): 2565-2573 .
Other cited types(0)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(4)

Get Citation

PDF

XML

Article Metrics

Article views (664) PDF downloads(40)

Genomic profile of pancreatic tumor in the coastal regions of Eastern China: A multicenter analysis of 40 cases

DOI: 10.3969/j.issn.1001-5256.2022.02.028

Abstract

References

Relative Articles

Supplements

Cited by

Periodical cited type(1)

Other cited types(0)

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Genomic profile of pancreatic tumor in the coastal regions of Eastern China: A multicenter analysis of 40 cases

DOI: 10.3969/j.issn.1001-5256.2022.02.028

Abstract

References

Relative Articles

Supplements

Cited by

Periodical cited type(1)

Other cited types(0)

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content