Page 84 - GPD-2-1

Gene & Protein in Disease A pan-cancer analysis of HMGB1

HMG-box domains (N-terminal A and center B), expression data transformed by log2 (TPM [Transcripts
which constitute the non-specific DNA binding region per million] + 1) were used for violin or box plots.
of HMGB1 and an acidic C-terminal tail . In general, The UALCAN (http://ualcan.path.uab.edu/analysis-
[6]
HMGB1 exists in the nucleus and helps maintain the prot.html) was used to analyze cancer omics data,
stability of the nucleus as a DNA chaperone. It plays a allowing us to analyze the protein expression of the
key role in DNA replication, V(D)J recombination, Clinical Proteomic Tumor Analysis Consortium (CPTAC)
transcription and chromatin remodeling. However, dataset . We investigated the expression level of HMGB1,
[12]
the expression of HMGB1 has also been found in either total protein or phosphoprotein, between primary
mitochondria, cytosol, and cell surface membranes, and tumor or normal tissues.
the protein can be released into the extracellular space .
[7]
Cytoplasmic HMGB1 participates in immune responses 2.2. Survival analysis
by regulating mitochondrial function, inhibiting
apoptosis, and increasing autophagy . On the membrane, To gain significant map data for overall survival (OS)
[8]
HMGB1 can activate platelets, promote neurite growth and disease-free survival (DFS) of HMGB1 in overall
and axonal sprouting, and induce cell migration. HMGB1 TCGA tumors, GEPIA2 was used in the analysis. Cutoff-
can be secreted into the extracellular environment as a low (50%) and cutoff-high (50%) values were used as
cytokine, and participates in many immune reactions expression thresholds to separate low and high expression
[11]
by promoting the maturation and activation of immune cohorts . The log-rank test was used in the hypothesis
cells and the production of cytokine . In addition, testing. Through the “Survival Analysis” plate of GEPIA2,
[9]
extracellular HMGB1 is able to interact with chemokines survival plots were obtained.
to advance immune responses . In a word, HMGB1, as 2.3. Genetic variation analysis
[10]
a multifunctional protein, plays different biological roles
under different circumstances, and more investigations Using the cBioPortal (https://www.cbioportal.org/) web [13-15] ,
are required to illustrate the potential effects. In pan- we collected the protein structure data, including
cancer analysis, to probe the expression profile of variation frequency, mutated site information, mutation
HMGB1 in different tumor types, databases (TGCA type, three-dimensional (3D) structure, and copy
and GEO) were used. Except for comparing HMGB1 number alteration (CNA) in overall TCGA tumors.
expression profiles in different tumor types, a number of We also obtained survival data, including progression-
factors such as survival status, genetic alteration, protein free survival, OS, disease-specific survival, and DFS
phosphorylation, and related cellular pathways were differences for the overall TCGA cancer types, regardless
also taken into account. This comprehensive analysis of whether there is HMGB1 genetic variation.
uncovers potential molecular mechanism of HMGB1 in
the pathogenesis and clinical prognosis of a variety of 2.4. Immune infiltration analysis
human cancers. TIMER2 was used to observe the relationship between
HMGB1expression and immune infiltrates among TCGA
2. Materials and methods tumors. Cancer-associated fibroblast was selected for
2.1. Gene expression analysis detailed analysis. The EPIC, MCPCOUNTER, XCELL, and
TIDE algorithms were used for estimations. The data was
To observe HMGB1 expression differences between tumor visualized as heatmaps and scatter plots.
and adjacent normal tissues, we put HMGB1 into the
“Gene_DE” section of tumor immune estimation resource, 2.5. HMGB1 enrichment analysis
version2 (TIMER2) web (http://timer.cistrome.org/). With STRING (https://string-db.org/) web was used for protein-
regard to some tumors without corresponding adjacent protein interaction network analysis. We set the following
normal tissues as a control (e.g., TCGA-Mesothelioma main parameters: minimum required interaction score
[MESO], TCGA-Sarcoma [SARC]), the “Expression
analysis-Box plot” plate of the Gene Expression Profiling (“low confidence [0.150]”), meaning of network edges
(“evidence”), maximum number of interactors to be
Interactive Analysis, version 2 (GEPIA2) web server displayed (“no more than 50 interactors” in first shell), and
(http://gepia2.cancer-pku.cn/#analysis) was used to active interaction sources (“experiments”).
[11]
obtain box plots of the Genotype-Tissue Expression
(GTEx) database, with log2FC (fold change) cutoff = 1, On the basis of the datasets of all TCGA tumors and
P-value cutoff = 0.01, and “Match TCGA normal and GTEx normal tissues, GEPIA2 was used to obtain the top 100
data.” HEPIA2 was applied to analyze HMGB1 expression HMGB1-related genes. We performed a pairwise Pearson’s
in different pathological stages of all TCGA cancers. The correlation analysis between HMGB1 and selected

Volume 2 Issue 1 (2023) 2 https://doi.org/10.36922/gpd.301