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: CXCL1

Gene summary for CXCL1

Gene summary.

Gene information	Species	Human
	Gene symbol	CXCL1
	Gene ID	2919
	Gene name	C-X-C motif chemokine ligand 1
	Gene Alias	FSP
	Cytomap	4q13.3
	Gene Type	protein-coding
	GO ID	GO:0002237
	UniProtAcc	P09341

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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
2919	CXCL1	GSM4909281	Human	Breast	IDC	1.99e-40	-1.07e+00	0.21
2919	CXCL1	GSM4909282	Human	Breast	IDC	4.03e-18	-9.02e-01	-0.0288
2919	CXCL1	GSM4909285	Human	Breast	IDC	7.36e-39	-1.08e+00	0.21
2919	CXCL1	GSM4909286	Human	Breast	IDC	3.55e-43	-1.09e+00	0.1081
2919	CXCL1	GSM4909287	Human	Breast	IDC	6.19e-35	-1.05e+00	0.2057
2919	CXCL1	GSM4909288	Human	Breast	IDC	1.10e-04	-8.47e-01	0.0988
2919	CXCL1	GSM4909289	Human	Breast	IDC	1.59e-07	-1.07e+00	0.1064
2919	CXCL1	GSM4909290	Human	Breast	IDC	1.60e-12	-8.30e-01	0.2096
2919	CXCL1	GSM4909291	Human	Breast	IDC	9.66e-27	-1.09e+00	0.1753
2919	CXCL1	GSM4909292	Human	Breast	IDC	3.01e-03	-1.03e+00	0.1236
2919	CXCL1	GSM4909293	Human	Breast	IDC	5.94e-34	-1.05e+00	0.1581
2919	CXCL1	GSM4909294	Human	Breast	IDC	5.79e-40	-1.08e+00	0.2022
2919	CXCL1	GSM4909295	Human	Breast	IDC	1.02e-09	-8.75e-01	0.0898
2919	CXCL1	GSM4909296	Human	Breast	IDC	6.42e-36	-1.06e+00	0.1524
2919	CXCL1	GSM4909297	Human	Breast	IDC	1.33e-31	-1.00e+00	0.1517
2919	CXCL1	GSM4909298	Human	Breast	IDC	3.55e-43	-1.09e+00	0.1551
2919	CXCL1	GSM4909299	Human	Breast	IDC	1.92e-26	-9.65e-01	0.035
2919	CXCL1	GSM4909300	Human	Breast	IDC	1.65e-05	-7.79e-01	0.0334
2919	CXCL1	GSM4909301	Human	Breast	IDC	1.29e-43	-1.09e+00	0.1577
2919	CXCL1	GSM4909302	Human	Breast	IDC	1.31e-39	-1.08e+00	0.1545

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗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:005076722	Skin	cSCC	regulation of neurogenesis	118/4864	364/18723	3.32e-03	1.81e-02	118
GO:004578529	Skin	cSCC	positive regulation of cell adhesion	139/4864	437/18723	3.39e-03	1.84e-02	139
GO:001097522	Skin	cSCC	regulation of neuron projection development	141/4864	445/18723	3.72e-03	1.99e-02	141
GO:005123527	Skin	cSCC	maintenance of location	106/4864	327/18723	5.17e-03	2.61e-02	106
GO:006156422	Skin	cSCC	axon development	146/4864	467/18723	5.50e-03	2.73e-02	146
GO:01403743	Skin	cSCC	antiviral innate immune response	9/4864	15/18723	5.52e-03	2.73e-02	9
GO:000315824	Skin	cSCC	endothelium development	49/4864	136/18723	6.00e-03	2.95e-02	49
GO:000961224	Skin	cSCC	response to mechanical stimulus	73/4864	216/18723	6.22e-03	3.04e-02	73
GO:00507729	Skin	cSCC	positive regulation of axonogenesis	31/4864	79/18723	6.63e-03	3.23e-02	31
GO:006056023	Skin	cSCC	developmental growth involved in morphogenesis	78/4864	234/18723	7.08e-03	3.40e-02	78
GO:005165128	Skin	cSCC	maintenance of location in cell	72/4864	214/18723	7.37e-03	3.47e-02	72
GO:000716224	Skin	cSCC	negative regulation of cell adhesion	98/4864	303/18723	7.45e-03	3.50e-02	98
GO:004592719	Skin	cSCC	positive regulation of growth	85/4864	259/18723	8.03e-03	3.73e-02	85
GO:190223021	Skin	cSCC	negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage	14/4864	29/18723	8.08e-03	3.74e-02	14
GO:199013823	Skin	cSCC	neuron projection extension	59/4864	172/18723	9.20e-03	4.20e-02	59
GO:200102122	Skin	cSCC	negative regulation of response to DNA damage stimulus	31/4864	81/18723	1.00e-02	4.40e-02	31
GO:005196213	Skin	cSCC	positive regulation of nervous system development	88/4864	272/18723	1.07e-02	4.66e-02	88
GO:0019730	Stomach	GC	antimicrobial humoral response	25/1159	122/18723	9.62e-08	6.08e-06	25
GO:0006959	Stomach	GC	humoral immune response	42/1159	317/18723	2.59e-06	1.10e-04	42
GO:0002237	Stomach	GC	response to molecule of bacterial origin	45/1159	363/18723	6.89e-06	2.57e-04	45

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513414	Breast	Precancer	Legionellosis	19/684	57/8465	4.62e-08	9.12e-07	6.98e-07	19
hsa0516718	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0541718	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0465716	Breast	Precancer	IL-17 signaling pathway	20/684	94/8465	4.74e-05	4.54e-04	3.48e-04	20
hsa0532312	Breast	Precancer	Rheumatoid arthritis	19/684	93/8465	1.30e-04	1.14e-03	8.73e-04	19
hsa051206	Breast	Precancer	Epithelial cell signaling in Helicobacter pylori infection	14/684	70/8465	1.21e-03	7.99e-03	6.12e-03	14
hsa0513415	Breast	Precancer	Legionellosis	19/684	57/8465	4.62e-08	9.12e-07	6.98e-07	19
hsa0516719	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0541719	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0465717	Breast	Precancer	IL-17 signaling pathway	20/684	94/8465	4.74e-05	4.54e-04	3.48e-04	20
hsa0532313	Breast	Precancer	Rheumatoid arthritis	19/684	93/8465	1.30e-04	1.14e-03	8.73e-04	19
hsa0512013	Breast	Precancer	Epithelial cell signaling in Helicobacter pylori infection	14/684	70/8465	1.21e-03	7.99e-03	6.12e-03	14
hsa0513422	Breast	IDC	Legionellosis	19/867	57/8465	1.89e-06	3.07e-05	2.29e-05	19
hsa0516723	Breast	IDC	Kaposi sarcoma-associated herpesvirus infection	38/867	194/8465	5.87e-05	5.96e-04	4.46e-04	38
hsa0532321	Breast	IDC	Rheumatoid arthritis	21/867	93/8465	3.69e-04	3.15e-03	2.36e-03	21
hsa0541724	Breast	IDC	Lipid and atherosclerosis	35/867	215/8465	3.67e-03	2.29e-02	1.71e-02	35
hsa0465721	Breast	IDC	IL-17 signaling pathway	18/867	94/8465	6.39e-03	3.30e-02	2.47e-02	18
hsa0513432	Breast	IDC	Legionellosis	19/867	57/8465	1.89e-06	3.07e-05	2.29e-05	19
hsa0516733	Breast	IDC	Kaposi sarcoma-associated herpesvirus infection	38/867	194/8465	5.87e-05	5.96e-04	4.46e-04	38
hsa0532331	Breast	IDC	Rheumatoid arthritis	21/867	93/8465	3.69e-04	3.15e-03	2.36e-03	21

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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
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	Breast	Precancer
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	Cervix	ADJ
CXCL1	CXCR2	CXCL1_CXCR2	CXCL	Cervix	ADJ
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	Cervix	CC
CXCL1	CXCR1	CXCL1_CXCR1	CXCL	Cervix	CC
CXCL1	CXCR2	CXCL1_CXCR2	CXCL	Cervix	CC
CXCL1	CXCR1	CXCL1_CXCR1	CXCL	Cervix	Healthy
CXCL1	CXCR2	CXCL1_CXCR2	CXCL	Cervix	Healthy
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	Cervix	Precancer
CXCL1	CXCR1	CXCL1_CXCR1	CXCL	Cervix	Precancer
CXCL1	CXCR2	CXCL1_CXCR2	CXCL	Cervix	Precancer
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	Endometrium	AEH
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	Endometrium	EEC
CXCL1	CXCR2	CXCL1_CXCR2	CXCL	Endometrium	EEC
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	Esophagus	Healthy
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	GC	Healthy
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	HNSCC	ADJ
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	HNSCC	Healthy
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	Liver	Precancer
CXCL1	ACKR1	CXCL1_ACKR1	CXCL	Lung	AIS

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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

CXCL1

SNV

Missense_Mutation

novel

c.125G>A

p.Arg42His

p.R42H

P09341

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CXCL1

SNV

Missense_Mutation

c.217G>A

p.Glu73Lys

p.E73K

P09341

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CXCL1

SNV

Missense_Mutation

novel

c.190N>C

p.Ser64Pro

p.S64P

P09341

protein_coding

tolerated(1)

benign(0.001)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CXCL1

SNV

Missense_Mutation

novel

c.293A>G

p.Glu98Gly

p.E98G

P09341

protein_coding

tolerated(0.05)

benign(0.007)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

CXCL1

SNV

Missense_Mutation

c.217G>A

p.Glu73Lys

p.E73K

P09341

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A5-A0GP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CXCL1

SNV

Missense_Mutation

novel

c.260N>G

p.Asn87Ser

p.N87S

P09341

protein_coding

deleterious(0.02)

probably_damaging(0.963)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CXCL1

SNV

Missense_Mutation

rs773534431

c.245G>A

p.Arg82Gln

p.R82Q

P09341

protein_coding

tolerated(1)

benign(0)

TCGA-AJ-A23O-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CXCL1

SNV

Missense_Mutation

c.217G>A

p.Glu73Lys

p.E73K

P09341

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

CXCL1

SNV

Missense_Mutation

c.152N>A

p.Gly51Glu

p.G51E

P09341

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-B5-A11N-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CXCL1

SNV

Missense_Mutation

c.297G>T

p.Lys99Asn

p.K99N

P09341

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

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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