P53-associated lncRNAs regulate immune functions and RNA-modifiers in gastric cancer
Zhao Huanjie,
Ihtisham Bukhari,
Li Fazhan,
Huijuan Wen,
Jingyun Wang,
Wu Wanqing,
Fu Yuming,
Tang Youcai,
Reem M. AlJowaie,
Ibrahim M. Aziz,
Chu Xiufeng,
Mi Yang,
Zheng Pengyuan
Affiliations
Zhao Huanjie
Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
Ihtisham Bukhari
Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China; Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
Li Fazhan
Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
Huijuan Wen
Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
Jingyun Wang
Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China; Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
Wu Wanqing
Department of Gastrointestinal Surgery, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
Fu Yuming
Department of Gastrointestinal Surgery, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
Tang Youcai
Department of Pediatrics, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
Reem M. AlJowaie
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
Ibrahim M. Aziz
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
Chu Xiufeng
Department of Oncology, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China; Corresponding author.
Mi Yang
Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China; Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China; Academy of Medical Science, Zhengzhou University, Zhongyuan, 450001, Zhengzhou, Henan China, China; Institute of Rehabilitation Medicine, Henan Academy of Innovations in Medical Sciences, Zhengzhou, Henan, China; Corresponding author.
Zheng Pengyuan
Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China; Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China; Academy of Medical Science, Zhengzhou University, Zhongyuan, 450001, Zhengzhou, Henan China, China; Institute of Rehabilitation Medicine, Henan Academy of Innovations in Medical Sciences, Zhengzhou, Henan, China; Corresponding author.
TP53, a guardian of the genome, suppresses or enhances tumors through various regulatory pathways. However, the role of p53-related long non-coding RNAs (lncRNAs) in immune regulation of tumor microenvironment and prognosis of gastric cancer (GC) is so far unelucidated. We analyzed the role of TP53-associated lncRNAs (obtained from the TP53LNC-DB database) in immune regulation, immune cell infiltration and RNA modification in gastric cancer. Firstly, using multivariate COX regression analysis, we identified eight lncRNAs related to the prognosis of GC. Furthermore, based on the expression of the lncRNA signature and risk score, the GC patients were divided into high-risk and low-risk groups. We found that M2-macrophages have significantly higher infiltration in the high-risk group. Similarly, significant differences in immune function (APC_co_stimulation, CCR, and checkpoint) and m6A modification (FTO, ZC3H13, YTHDC1, and RBM15), and m5C modification (NOP2 and TET1) between both groups were also observed. These signature lncRNAs were also positively associated with oxidative stress-related genes (MPO, MAPK14, HMOX1, and APP). Additionally, we found that high expression of GAS5 and low expression of MALAT1 in Helicobacter pylori (H-pylori) positive GC patients. Finally, GC patients in the low-risk group showed higher resistance to immunotherapy while patients in the high-risk group were more sensitive to various chemotherapy drugs. Based on these findings, we conclude that p53-associated lncRNAs signature could potentially predict the immune status and overall survival, and may also be used for risk management and planning immunotherapy for gastric cancer patients.
