Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: HRC

Gene summary for HRC

Gene summary.

Gene information	Species	Human
	Gene symbol	HRC
	Gene ID	3270
	Gene name	histidine rich calcium binding protein
	Gene Alias	HRC
	Cytomap	19q13.33
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	P23327

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
3270	HRC	Pt13.b	Human	Liver	HCC	2.35e-06	1.72e-01	0.0251
3270	HRC	S014	Human	Liver	HCC	5.22e-15	5.63e-01	0.2254
3270	HRC	S015	Human	Liver	HCC	3.91e-22	1.14e+00	0.2375
3270	HRC	S016	Human	Liver	HCC	4.86e-15	5.10e-01	0.2243

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:00219154	Liver	HCC	neural tube development	82/7958	152/18723	2.83e-03	1.33e-02	82
GO:00551191	Liver	HCC	relaxation of cardiac muscle	13/7958	17/18723	4.77e-03	2.02e-02	13
GO:00018384	Liver	HCC	embryonic epithelial tube formation	66/7958	121/18723	4.94e-03	2.07e-02	66
GO:00860642	Liver	HCC	cell communication by electrical coupling involved in cardiac conduction	17/7958	25/18723	8.94e-03	3.45e-02	17
GO:00721754	Liver	HCC	epithelial tube formation	70/7958	132/18723	9.29e-03	3.57e-02	70
GO:190184411	Liver	HCC	regulation of cell communication by electrical coupling involved in cardiac conduction	9/7958	11/18723	9.51e-03	3.60e-02	9
GO:0010882	Liver	HCC	regulation of cardiac muscle contraction by calcium ion signaling	18/7958	27/18723	9.75e-03	3.66e-02	18
GO:000164911	Liver	HCC	osteoblast differentiation	115/7958	229/18723	1.08e-02	3.99e-02	115
GO:00351484	Liver	HCC	tube formation	77/7958	148/18723	1.20e-02	4.39e-02	77
GO:0010881	Liver	HCC	regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	15/7958	22/18723	1.35e-02	4.80e-02	15
GO:005109820	Oral cavity	OSCC	regulation of binding	212/7305	363/18723	3.88e-14	2.15e-12	212
GO:004339318	Oral cavity	OSCC	regulation of protein binding	121/7305	196/18723	8.92e-11	2.73e-09	121
GO:005109920	Oral cavity	OSCC	positive regulation of binding	105/7305	173/18723	5.88e-09	1.26e-07	105
GO:001605510	Oral cavity	OSCC	Wnt signaling pathway	227/7305	444/18723	1.10e-07	1.87e-06	227
GO:019873810	Oral cavity	OSCC	cell-cell signaling by wnt	227/7305	446/18723	1.75e-07	2.86e-06	227
GO:003209210	Oral cavity	OSCC	positive regulation of protein binding	54/7305	85/18723	4.05e-06	4.71e-05	54
GO:000150310	Oral cavity	OSCC	ossification	203/7305	408/18723	5.54e-06	6.19e-05	203
GO:003011110	Oral cavity	OSCC	regulation of Wnt signaling pathway	165/7305	328/18723	1.87e-05	1.80e-04	165
GO:000184110	Oral cavity	OSCC	neural tube formation	60/7305	102/18723	3.90e-05	3.43e-04	60
GO:000164910	Oral cavity	OSCC	osteoblast differentiation	118/7305	229/18723	7.51e-05	5.85e-04	118

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

HRC

SNV

Missense_Mutation

novel

c.751G>A

p.Asp251Asn

p.D251N

P23327

protein_coding

tolerated(0.12)

possibly_damaging(0.685)

TCGA-A2-A0SY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

arimidex

HRC

SNV

Missense_Mutation

novel

c.1345N>C

p.Glu449Gln

p.E449Q

P23327

protein_coding

tolerated(0.3)

benign(0.067)

TCGA-A2-A3Y0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HRC

SNV

Missense_Mutation

c.1431N>C

p.Leu477Phe

p.L477F

P23327

protein_coding

tolerated(0.12)

benign(0.044)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HRC

SNV

Missense_Mutation

c.1758N>G

p.Ile586Met

p.I586M

P23327

protein_coding

deleterious(0)

possibly_damaging(0.854)

TCGA-AO-A1KR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

HRC

SNV

Missense_Mutation

novel

c.811N>T

p.His271Tyr

p.H271Y

P23327

protein_coding

tolerated(0.06)

probably_damaging(0.982)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HRC

SNV

Missense_Mutation

rs766836022

c.1951N>A

p.Glu651Lys

p.E651K

P23327

protein_coding

deleterious(0)

possibly_damaging(0.885)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

HRC

SNV

Missense_Mutation

novel

c.1600G>A

p.Glu534Lys

p.E534K

P23327

protein_coding

deleterious(0)

possibly_damaging(0.587)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

HRC

SNV

Missense_Mutation

c.68N>A

p.Pro23His

p.P23H

P23327

protein_coding

deleterious(0)

possibly_damaging(0.543)

TCGA-E2-A158-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

arimidex

HRC

SNV

Missense_Mutation

novel

c.704G>C

p.Gly235Ala

p.G235A

P23327

protein_coding

tolerated(0.51)

benign(0)

TCGA-C5-A1M6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HRC

SNV

Missense_Mutation

rs563550433

c.872G>A

p.Arg291His

p.R291H

P23327

protein_coding

tolerated(1)

benign(0)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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