Expression and prognostic value of prohibitin in gastrointestinal cancers based on bioinformatics

Xiaofeng LI; Xixi LIU; Ziqing SONG; Mingzheng TANG; Hui CAI; Lingyun ZHANG

doi:10.16016/j.2097-0927.202306086

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Expression and prognostic value of prohibitin in gastrointestinal cancers based on bioinformatics

Basic Medicine | 更新时间：2026-01-09

- Expression and prognostic value of prohibitin in gastrointestinal cancers based on bioinformatics
- Journal of Army Medical University Vol. 46, Issue 16, Pages: 1838-1848(2024)
- 作者机构：
  
  1.730000 兰州，甘肃中医药大学第一临床医学院
  2.730000 兰州，甘肃省人民医院普外科
  3.730050 兰州，甘肃省中医院外科临床中心
- 作者简介：
- 基金信息：
  
  the Natural Science Foundation of Gansu Province(20JR5RA159);the Project of Postgraduate Innovation and Entre preneurship Fund of Gansu University of Chinese Medicine in 2023(32号)
- DOI：10.16016/j.2097-0927.202306086
  CLC： R341;R730.23;R735
- Received：24 June 2023，
  
  Revised：2023-11-13，
  
  Published：30 August 2024
- 稿件说明：
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Xiaofeng LI, Xixi LIU, Ziqing SONG, et al. Expression and prognostic value of prohibitin in gastrointestinal cancers based on bioinformatics[J]. Journal of Army Medical University, 2024, 46(16): 1838-1848.
DOI：

Xiaofeng LI, Xixi LIU, Ziqing SONG, et al. Expression and prognostic value of prohibitin in gastrointestinal cancers based on bioinformatics[J]. Journal of Army Medical University, 2024, 46(16): 1838-1848. DOI： 10.16016/j.2097-0927.202306086.

摘要

目的

探索肿瘤组织中抑制素(prohibitin

PHB

)的表达情况

分析其对消化系统恶性肿瘤(digestive system malignant tumor

DT)患者预后的影响以及作用机制。

方法

① 使用癌

症基因组图谱(the Cancer Genome Atlas

TCGA)和基因型-组织表达(Genotype-Tissue Expression

GTEx)数据库比较肿瘤组织和正常组织中

PHB

的表达差异。②收集2023年10月甘肃省人民医院诊治的5对胃癌及癌旁组织和5对结肠癌及癌旁组织

RT-qPCR检测

PHB

mRNA表达水平。③采用RT-qPCR和Western blot检测正常胃黏膜细胞(GES-1)和胃癌细胞(AGS、MKN45和HGC27)、正常结肠细胞NCM-460和人结肠癌细胞株SW480中

PHB

的表达差异。④利用R语言分析

PHB

对DT患者预后、肿瘤微环境、肿瘤突变负荷和微卫星不稳定性的影响。⑤采用CIBERSORT算法分析肿瘤组织中

PHB

表达与肿瘤免疫细胞浸润之间的相关性。基因集富集分析(Gene Set Enrichment Analysis

GSEA)探讨

PHB

的生物学功能。⑥利用R语言分析

PHB

与药物敏感性的关系。

结果

①

PHB

在结肠癌、胆管癌、食管癌、肝癌、直肠癌和胃癌组织中均显著高表达(

0.01)。②RT-qPCR和Western blot检测结果显示

PHB

在胃癌和结肠癌组织和细胞中高表达(

0.01)。③

PHB

的差异表达与肝癌(

=0.002)预后不良相关。在胆管癌、胃癌、胰腺癌、肝癌和食管癌中

PHB

与肿瘤突变负荷和微卫星不稳定性呈正相关(

0.05)。④

PHB

的表达在结肠癌中与M2型巨噬细胞呈正相关(

=0.03);在胆管癌中与活化CD4

记忆T细胞呈正相关(

0.05);在食管癌中与活化肥大细胞呈正相关(

=0.03);在肝癌中与M0、M2型巨噬细胞和单核细胞呈正相关(

0.05);在直肠癌中与静息树突状细胞、嗜酸性粒细胞和活化CD4

记忆T细胞呈正相关(

0.05);在胃癌中与M0型巨噬细胞、活化肥大细胞、中性粒细胞、静息自然杀伤细胞、活化CD4

记忆T细胞和滤泡辅助性T细胞呈正相关(

0.05)。⑤

PHB

在Ⅰ类受体、PPAR和钙离子信号通路中主要富集(

0.05)。⑥

PHB

的表达与氨萘非特、普拉西诺特和阿比特龙等13种药物敏感性呈正相关(

0.05)。

结论

PHB

表达与DT中多种免疫细胞浸润及不良预后有关

其可能成为新型DT生物标志物及潜在的免疫调节靶点。

Abstract

Objective

To explore the expression of prohibitin (PHB) in tumor tissues and analyze its effect on the prognosis of patients with digestive system malignant tumor (DT) and its mechanism.

Methods

① The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database were used to compare the expression of PHB in tumor tissues and normal tissues.②Five pairs of gastric cancer and adjacent tissues and 5 pairs of colon cancer and adjacent tissues were collected

and RT-qPCR was used to verify the mRNA expression levels.③RT-qPCR and Western blotting were used to verify the differential expression of PHB in normal gastric mucosa cells (GES-1)

gastric cancer cells (AGS

MKN45 and HGC27)

normal colon cells NCM-460 and human colon cancer cell line SW480.④R language was used to analyze the effect of PHB on the prognosis

tumor microenvironment

tumor mutation burden and microsatellite instability of DT patients.⑤CIBERSORT algorithm was used to study the correlation between PHB expression in tumor tissues and tumor immune cell infiltration.Gene Set Enrichment Analysis (GSEA) was used to explore the biological function of PHB.⑥R language was used to analyze the relationship between PHB and drug sensitivity.

Results

① PHB was highly expressed in colon cancer

cholangiocarcinoma

esophageal cancer

liver cancer

rectal cancer and gastric cancer (

0.01).②RT-qPCR and Western blotting showed that PHB was highly expressed in the tissues and cell lines of gastric cancer (

0.01) and colon cancer (

0.01).③The differential expression of PHB was associated with poor prognosis of hepatocellular carcinoma (

=0.002).In cholangiocarcinoma

gastric cancer

pancreatic cancer

liver cancer and esophageal cancer

PHB was positively correlated with tumor mutation burden and microsatellite instability (

0.05).④PHB was positively correlated with M2 macrophages in colon cancer (

=0.03).In cholangiocarcinoma

it was positively correlated with activated CD4

memory T cells (

0.05).In esophageal carcinoma

it was positively correlated with activated hypertrophy (

=0.03).It was positively correlated with M0 and M2 macrophages and monocytes in hepatocellu

lar carcinoma (

0.05).It was positively correlated with resting dendritic cells

eosinophils and activated CD4

memory T cells in rectal cancer (

0.05).It was positively correlated with M0 macrophages

activated mast cells

neutrophils

resting natural killer cells

activated CD4

memory T cells and follicular helper T cells in gastric cancer (

0.05).⑤PHB was mainly enriched in class I receptors

PPAR and calcium signaling pathways (

0.05).⑥ The expression of PHB was positively correlated with the sensitivity of 13 drugs

including ammonafide

prasinolide and abiraterone (

0.05).

Conclusion

The expression of PHB is significantly related to the infiltration of various immune cells in DT and poor prognosis in DT patients

which may become a new biomarker and potential immunomodulatory target of DT.

关键词

Keywords

references

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