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: HOPX

Gene summary for HOPX

Gene summary.

Gene information	Species	Human
	Gene symbol	HOPX
	Gene ID	84525
	Gene name	HOP homeobox
	Gene Alias	CAMEO
	Cytomap	4q12
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q9BPY8

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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
84525	HOPX	CA_HPV_1	Human	Cervix	CC	4.78e-02	-1.67e-01	0.0264
84525	HOPX	CA_HPV_3	Human	Cervix	CC	2.75e-42	9.65e-01	0.0414
84525	HOPX	N_HPV_2	Human	Cervix	N_HPV	3.42e-07	3.73e-01	-0.0131
84525	HOPX	CCII_1	Human	Cervix	CC	1.10e-03	-2.85e-01	0.3249
84525	HOPX	H2	Human	Cervix	HSIL_HPV	1.61e-10	5.04e-01	0.0632
84525	HOPX	T1	Human	Cervix	CC	3.50e-05	-2.71e-01	0.0918
84525	HOPX	LZE8T	Human	Esophagus	ESCC	2.32e-04	1.13e-02	0.067
84525	HOPX	LZE24T	Human	Esophagus	ESCC	7.89e-07	2.03e-01	0.0596
84525	HOPX	LZE6T	Human	Esophagus	ESCC	3.62e-04	6.92e-01	0.0845
84525	HOPX	P4T-E	Human	Esophagus	ESCC	3.70e-28	9.47e-01	0.1323
84525	HOPX	P5T-E	Human	Esophagus	ESCC	2.29e-23	6.80e-01	0.1327
84525	HOPX	P9T-E	Human	Esophagus	ESCC	2.58e-38	1.18e+00	0.1131
84525	HOPX	P11T-E	Human	Esophagus	ESCC	1.88e-02	1.29e+00	0.1426
84525	HOPX	P12T-E	Human	Esophagus	ESCC	1.33e-36	1.06e+00	0.1122
84525	HOPX	P15T-E	Human	Esophagus	ESCC	9.42e-04	3.15e-01	0.1149
84525	HOPX	P20T-E	Human	Esophagus	ESCC	8.59e-58	1.63e+00	0.1124
84525	HOPX	P21T-E	Human	Esophagus	ESCC	8.71e-82	4.36e+00	0.1617
84525	HOPX	P23T-E	Human	Esophagus	ESCC	3.40e-10	5.76e-01	0.108
84525	HOPX	P26T-E	Human	Esophagus	ESCC	3.63e-33	8.67e-01	0.1276
84525	HOPX	P27T-E	Human	Esophagus	ESCC	6.03e-38	9.38e-01	0.1055

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:005109810	Cervix	CC	regulation of binding	80/2311	363/18723	1.32e-07	6.42e-06	80
GO:00310996	Cervix	CC	regeneration	46/2311	198/18723	1.43e-05	2.84e-04	46
GO:00017018	Cervix	CC	in utero embryonic development	71/2311	367/18723	7.21e-05	1.00e-03	71
GO:00605375	Cervix	CC	muscle tissue development	76/2311	403/18723	9.76e-05	1.27e-03	76
GO:00459277	Cervix	CC	positive regulation of growth	53/2311	259/18723	1.33e-04	1.64e-03	53
GO:00165705	Cervix	CC	histone modification	84/2311	463/18723	1.70e-04	2.01e-03	84
GO:00147064	Cervix	CC	striated muscle tissue development	72/2311	384/18723	1.76e-04	2.07e-03	72
GO:00433939	Cervix	CC	regulation of protein binding	42/2311	196/18723	2.27e-04	2.55e-03	42
GO:00486386	Cervix	CC	regulation of developmental growth	61/2311	330/18723	7.69e-04	6.85e-03	61
GO:00426924	Cervix	CC	muscle cell differentiation	69/2311	384/18723	8.12e-04	7.09e-03	69
GO:0042246	Cervix	CC	tissue regeneration	19/2311	72/18723	9.11e-04	7.81e-03	19
GO:00434032	Cervix	CC	skeletal muscle tissue regeneration	12/2311	37/18723	1.15e-03	9.39e-03	12
GO:00303245	Cervix	CC	lung development	36/2311	177/18723	1.64e-03	1.26e-02	36
GO:00303235	Cervix	CC	respiratory tube development	36/2311	181/18723	2.46e-03	1.71e-02	36
GO:00018291	Cervix	CC	trophectodermal cell differentiation	7/2311	17/18723	2.72e-03	1.85e-02	7
GO:00605413	Cervix	CC	respiratory system development	39/2311	203/18723	3.18e-03	2.07e-02	39
GO:00511464	Cervix	CC	striated muscle cell differentiation	50/2311	283/18723	5.53e-03	3.19e-02	50
GO:00486395	Cervix	CC	positive regulation of developmental growth	33/2311	174/18723	7.65e-03	4.07e-02	33
GO:003109913	Cervix	HSIL_HPV	regeneration	20/737	198/18723	1.12e-04	2.33e-03	20
GO:001470611	Cervix	HSIL_HPV	striated muscle tissue development	28/737	384/18723	1.35e-03	1.55e-02	28

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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

HOPX

SNV

Missense_Mutation

novel

c.40N>A

p.Glu14Lys

p.E14K

Q9BPY8

protein_coding

tolerated_low_confidence(0.29)

benign(0.053)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HOPX

SNV

Missense_Mutation

c.301N>C

p.Phe101Leu

p.F101L

Q9BPY8

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.903)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

HOPX

SNV

Missense_Mutation

novel

c.205N>T

p.Asp69Tyr

p.D69Y

Q9BPY8

protein_coding

tolerated_low_confidence(0.89)

benign(0.092)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

HOPX

SNV

Missense_Mutation

novel

c.258A>C

p.Glu86Asp

p.E86D

Q9BPY8

protein_coding

tolerated_low_confidence(0.07)

possibly_damaging(0.558)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HOPX

SNV

Missense_Mutation

novel

c.295N>A

p.Asp99Asn

p.D99N

Q9BPY8

protein_coding

deleterious_low_confidence(0)

benign(0.003)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HOPX

SNV

Missense_Mutation

rs535907950

c.314N>T

p.Pro105Leu

p.P105L

Q9BPY8

protein_coding

deleterious_low_confidence(0)

benign(0.013)

TCGA-D1-A17D-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

HOPX

SNV

Missense_Mutation

novel

c.295N>A

p.Asp99Asn

p.D99N

Q9BPY8

protein_coding

deleterious_low_confidence(0)

benign(0.003)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

HOPX

SNV

Missense_Mutation

novel

c.53N>T

p.Thr18Ile

p.T18I

Q9BPY8

protein_coding

tolerated_low_confidence(0.11)

possibly_damaging(0.522)

TCGA-2Y-A9GZ-01

Liver

liver hepatocellular carcinoma

Female

>=65

I/II

Targeted Molecular therapy

sorafenib

HOPX

SNV

Missense_Mutation

c.170N>T

p.Glu57Val

p.E57V

Q9BPY8

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-43-5668-01

Lung

lung squamous cell carcinoma

Male

>=65

I/II

Other, specify in notesMAGE3-AS15-NSC-003

clinical

HOPX

SNV

Missense_Mutation

c.86A>T

p.Glu29Val

p.E29V

Q9BPY8

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.506)

TCGA-66-2793-01

Lung

lung squamous cell carcinoma

Male

>=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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