The idea of "6 points + gene family" without experiment~

Introduction

Protein lysine demethylase KDM5 Family epigenetic abnormalities are associated with a variety of cancers .

Background introduction

Today, Xiaobian brings you a pure letter article about gene family , All results can be easily reproduced in online tools or software . The title of the article is Expression, Prognostic Value, and Functional Mechanism of the KDM5 Family in Pancreatic Cancer, Published in Front. Cell Dev. Biol. On , Influencing factors 6.6 branch .

Data is introduced

The data come from TCGA, But it is mentioned in the original text , The analysis is done by online tools , Include

cBioPortal：https://www.cbioportal.org/

Kaplan-Meier Plotter：http://kmplot.com/analysis/

TIMER：http://timer.cistrome.org/

LinkedOmics：http://www.linkedomics.org/login.php

STRING：https://string-db.org/

GeneCards：https://www.genecards.org/

Metascape：https://metascape.org/gp/index.html

TISIDB：http://cis.hku.hk/TISIDB/

GSCA Lite：http://bioinfo.life.hust.edu.cn/web/GSCALite/

Result analysis

01

KDM5 Family expression in pancreatic cancer

Compared with normal tissue ,KDM5A/B/C stay PAAD、 Mammary cancer （BRCA） And gastric adenocarcinoma （STAD） etc. 12 The expression was significantly up-regulated in tumor tissues （ chart 1A–C）. by comparison ,KDM5D stay 24 The expression in the tumor tissues decreased significantly , for example PAAD,BRCA And prostate cancer （PRAD）（ chart 1D）. Sum up ,KDM5A/B/C Include PAAD It is obviously overexpressed in a variety of tumor tissues , and KDM5D The expression of is obviously down regulated , indicate KDM5 The expression of family members is closely related to the occurrence and development of a variety of malignant tumors, including pancreatic cancer .

chart 1

02

KDM5 Family mutations and prognosis in pancreatic cancer

Author use cBioPortal Online tools analyze KDM5 Family mutations .KDM5 The family comes from patients with pancreatic cancer 17 Samples （11%） There are two or more types of genetic variation in （ chart 2A）. The most common variation occurs in KDM5A/B In gene （5%）. The main types of mutation are amplification and missense mutation . Besides ,2.7% The variation of occurs in KDM5C in , The most common type of variation is deep deletion , And in the KDM5D No related mutation was detected in the gene .

chart 2

The author analyzes KDM5 Clinical and pathological features of patients with familial gene mutations and patients without mutations . Results show , Patients with a history of alcohol consumption and mucinous adenocarcinoma of pancreatic cancer are more likely to develop KDM5 Familial gene mutations （ chart 2B-C）. majority KDM5A Patients with gene mutations have a family history of breast cancer and melanoma or pathological pancreatic cancer subtype of pancreatic mucinous adenocarcinoma （ chart 2D-E）. majority KDM5B People with genetic mutations have a history of drinking （ chart 2F）, majority KDM5C Patients with gene mutations have a family history of breast cancer , The history of chronic pancreatitis and the tumor grade of pancreatic cancer were higher （ chart 2G-I）.

In the face of KDM5 In the analysis of prognostic characteristics of patients with familial gene mutations and patients without mutations , Not found KDM5 Effect of familial gene mutations on patients with pancreatic cancer OS and DFS Have a significant impact on , This may be related to the small sample size of patients . in summary , Patients with pancreatic cancer KDM5A/B/C The incidence of gene mutation is high , And have a history of drinking 、 Family history of breast cancer 、 Patients with a family history of melanoma or a history of chronic pancreatitis KDM5A/B/C Mutations are more likely .

03

KDM5 Prognosis of family gene expression

KDM5A The high expression of CD34 was significantly correlated with poor therapeutic effect and higher tumor grade .KDM5B High expression and age ≤65 year , No history of diabetes , Higher tumor grade , More advanced clinical stages and more advanced T There is a significant correlation between stages .KDM5C The high expression of E .KDM5D There was a significant correlation between male and smoking history .KDM5A and KDM5B The high level of expression of β - lactamase can increase the malignant degree of pancreatic cancer , The prognosis of patients is worse , Further confirmation KDM5 Members of the family may be proto oncogenes of pancreatic cancer .

Author use Kaplan Meier The curve analyses KDM5 Correlation between family gene expression and prognosis of patients with pancreatic cancer . It turns out that ,KDM5A The up-regulated expression of OS and RFS of .KDM5D Down regulation of expression and shorter OS and RFS relevant .KDM5B and KDM5C The overexpression of is different from that of short OS And shorter RFS significant correlation （ chart 3A,B）.

The above results show that ,KDM5 Abnormal family expression can be used as a biomarker to predict the prognosis of patients with pancreatic cancer .

chart 3

04

KDM5 The enrichment of family genes

In order to explore pancreatic cancer KDM5 Interactions between family genes and their co expressed genes , from LinkedOmics From the database KDM5 The family's 800 Co expression genes , And mapped the pattern of KDM5 Volcanic map of families and coexpressed genes （ chart 4A). Use Metascape The database analyzes this 800 Gene GO and KEGG access .

Results show BP The term “ Peptide metabolism process ”,“ Chromatin tissue ” and “ Cell pair DNA Responses to injury stimuli ” Significantly enriched （ chart 4B）. Enriched CC Items mainly include “ Cytoplasmic ribosomes ”,“ Transferase complex ” and “ Mitochondrial envelope ”（ chart 4C）. Enriched MF The terms mainly include “ The structural components of ribosomes ”,“ Chromatin binding ” and “ Transcription factor binding ”（ chart 4D）.KEGG Path analysis shows that , Target genes are mainly related to terminology “ Ribosome ”,“ Chemical carcinogenesis - Reactive oxygen species ” and “ Transcriptional disorders in cancer ” of （ chart 4E）.

chart 4

For further analysis KDM5 Family and the mechanism of its coexpressive genes , The front... Is visualized in the heat map 50 Positive correlation genes （ chart 5A） And the former 50 Negative correlation genes （ chart 5B）. The functions of related genes include transcriptional regulation , Protein modification ,DNA Damage repair , Cell cycle regulation and cell migration regulation .GeneCards For comments and KDM5A/B/C Express positively related pre - 10 Genes and their association with KDM5D Express negatively correlated pre - 10 A gene . The functions of genes include transcriptional regulation 、 Protein modification 、 Translation regulation 、 cell cycle regulation 、 Cell migration regulation 、 Regulation of cell proliferation and apoptosis .

KRAS It can induce transcriptional silencing of tumor suppressor genes , Its mutation produces a modified protein that drives the occurrence and development of pancreatic cancer .KRAS Genes and KDM5B There is a positive correlation between the expression of （ chart 5A）. meanwhile ,KDM5A/B/C The expression level of KRAS、BRCA1、BRCA2、ATM、SLC16A4 and RABL3 There is a positive correlation between the expression of .

Last , Use TIMER The database analyzes KDM5 The relationship between family members , The results showed that the expression of each member was significantly positively correlated ：KDM5A and KDM5B The correlation is the strongest （cor = 0.594）（ chart 5D）.

Sum up ,KDM5 Members of the family can be associated with a variety of pathogenic genes in pancreatic cancer 、 Transcriptional regulators 、 Protein modifying factors 、DNA Damage repair factor 、 Cell cycle regulators 、 Cell migration regulators, etc , Include and “ Chemical carcinogenesis — Reactive oxygen species ” and “ Cancer transcription disorders ” Related factors , Participate in the occurrence and development of pancreatic cancer .

chart 5

05

PPI Network and enrichment

Author use STRING Analysis of the KDM5 Protein expression of family members and related genes , And KDM5 Family protein protein interactions （PPI） The strongest 9 A gene .PPI The network includes 9 Gene nodes and 24 One side （ chart 6A）. It turns out that ,KDM5A/B/C Protein expression and HDAC1 Is closely related to protein expression .

Next , The author analyzes the relation between KDM5 The family proteins have the strongest interactions 9 Gene GO and KEGG Enrichment pathways （ chart 6B）.GO Analysis results show that BP term “ Histone lysine demethylation ”,“ Histone demethylation ” and “ Protein demethylation ” Significantly enriched .CC Items mainly include “ Histone methyltransferase complex ”、“ Methyltransferase complex ” and “Sin3 compound ”.MF Items mainly include “ Histone demethylase activity ”、“ Demethylase activity ” and “ Nuclear pressor activity ”.KEGG Path analysis shows that , The target genes are mainly related to “ Longevity regulation pathway ”、“ Notch signaling pathway ” and “ Amphetamine addiction ” And so on .

Sum up ,KDM5 Family proteins may be associated with HDAC1 And other proteins have strong interactions , Modify histones H3 Lysine , Acting in many ways , Include “ Longevity regulation pathway ” and “ Notch signaling pathway ”, These play a regulatory role in the proliferation of pancreatic cancer cells .

chart 6

06

KDM5 Familial immune infiltration

The author uses TIMER Database exploration KDM5 Relationship between family gene expression and lymphocyte infiltration level .KDM5A/B/C Up regulation of expression and B cells 、CD8 T cells 、 Macrophages 、 Neutrophils 、 Dendritic cells are associated with increased infiltration of other infiltrating lymphocytes （ chart 7A–C）,KDM5D Up regulation of expression and B cells 、CD8 T cells 、 Macrophages 、 Neutrophils 、 Dendritic cells were not associated with increased infiltration of other infiltrating lymphocytes （ chart 7D).

Author use TISIDB Database analysis of pancreatic cancer KDM5 Family expression and immunostimulatory molecules （ chart 7E）, Immunosuppressive molecules （ chart 7F）,MHC molecular （ chart 7G）, Chemokines （ chart 7H） And chemokine receptors （ chart 7I） The correlation between . It turns out that ,KDM5A/B/C The up-regulated expression of NT5E、TNFSF4 and TNFSF15 And other immune stimulating molecules 、CD274 and TGFBR1 And other immunosuppressive molecules 、TAP2 etc. MHC molecular 、CCL24 And other chemokines CCR8 and CCR9 It is related to the increased expression of chemokine receptors （ chart 7E–I）.

Last , Use GSCALite Tools to analyze KDM5 The relationship between the expression of family genes and the sensitivity of current immune or targeted therapy in pancreatic cancer （ chart 7J）. It turns out that ,KDM5A and KDM5C The expression level is related to many targeted or chemotherapeutic drugs in pancreatic cancer （ Including acitinib and gemcitabine ） The sensitivity of . therefore ,KDM5 Family may be a new target for predicting drug sensitivity and developing multi-target combination therapy for pancreatic cancer .

chart 7

Editor's summary

This paper analyzes KDM5 Family expression in pancreatic cancer 、 mutation 、 Existence 、 Enrichment pathway 、 Immune infiltration and drug sensitivity , Use only online tools and software , It was published without supplementary experiments 6 Divide the article , It's worth learning ！