Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica.

Autor: Liu Z; Zhejiang Cancer Institute, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, People's Republic of China., Hong LL; Zhejiang Cancer Institute, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, People's Republic of China., Zheng JS; Zhejiang Cancer Institute, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, People's Republic of China., Ling ZN; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People's Republic of China., Zhang ZL; Department of Oncology, The Second Clinical Medical College of Zhejiang, Chinese Medicine University, Hangzhou, Zhejiang Province, People's Republic of China., Qi YN; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China., Zhang XY; Department of Oncology, The Second Clinical Medical College of Zhejiang, Chinese Medicine University, Hangzhou, Zhejiang Province, People's Republic of China., Zhu TY; Department of Digestive Oncology, The First Affiliated Hospital of Wenzhou Medical University, The First Provincial Wenzhou Hospital of Zhejiang, Wenzhou, 325000, China., Wang JL; Zhejiang Cancer Institute, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, People's Republic of China., Han J; Zhejiang Cancer Institute, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, People's Republic of China., Chen XL; Zhejiang Cancer Institute, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, People's Republic of China.; Department of Gastric Surgery, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, People's Republic of China., Yu QM; Department of Gastric Surgery, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, People's Republic of China., Wang S; Department of Endoscopy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China., Li P; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China., Ling ZQ; Zhejiang Cancer Institute, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, People's Republic of China. lingzq@zjcc.org.cn.
Jazyk: angličtina
Zdroj: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association [Gastric Cancer] 2023 Mar; Vol. 26 (2), pp. 203-219. Date of Electronic Publication: 2022 Nov 30.
DOI: 10.1007/s10120-022-01353-2
Abstrakt: Background: Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined.
Methods: We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP.
Results: Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity.
Conclusions: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.
(© 2022. The Author(s).)
Databáze: MEDLINE
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