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: SPG7

Gene summary for SPG7

Gene summary.

Gene information	Species	Human
	Gene symbol	SPG7
	Gene ID	6687
	Gene name	SPG7 matrix AAA peptidase subunit, paraplegin
	Gene Alias	CAR
	Cytomap	16q24.3
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	Q9UQ90

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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
6687	SPG7	LZE2D	Human	Esophagus	HGIN	3.25e-04	3.13e-01	0.0642
6687	SPG7	LZE2T	Human	Esophagus	ESCC	5.74e-14	6.72e-01	0.082
6687	SPG7	LZE4T	Human	Esophagus	ESCC	2.89e-14	4.17e-01	0.0811
6687	SPG7	LZE5T	Human	Esophagus	ESCC	2.28e-07	4.73e-01	0.0514
6687	SPG7	LZE7T	Human	Esophagus	ESCC	4.95e-13	8.03e-01	0.0667
6687	SPG7	LZE8T	Human	Esophagus	ESCC	2.15e-12	3.11e-01	0.067
6687	SPG7	LZE20T	Human	Esophagus	ESCC	1.39e-10	5.36e-01	0.0662
6687	SPG7	LZE21D1	Human	Esophagus	HGIN	2.70e-06	5.60e-01	0.0632
6687	SPG7	LZE22D1	Human	Esophagus	HGIN	1.16e-05	2.26e-01	0.0595
6687	SPG7	LZE22T	Human	Esophagus	ESCC	9.39e-10	3.50e-01	0.068
6687	SPG7	LZE24T	Human	Esophagus	ESCC	7.60e-21	5.89e-01	0.0596
6687	SPG7	LZE21T	Human	Esophagus	ESCC	1.08e-05	6.60e-01	0.0655
6687	SPG7	P1T-E	Human	Esophagus	ESCC	2.94e-27	1.13e+00	0.0875
6687	SPG7	P2T-E	Human	Esophagus	ESCC	4.69e-39	6.42e-01	0.1177
6687	SPG7	P4T-E	Human	Esophagus	ESCC	7.11e-28	5.98e-01	0.1323
6687	SPG7	P5T-E	Human	Esophagus	ESCC	1.84e-20	3.62e-01	0.1327
6687	SPG7	P8T-E	Human	Esophagus	ESCC	3.48e-49	8.01e-01	0.0889
6687	SPG7	P9T-E	Human	Esophagus	ESCC	2.61e-19	3.97e-01	0.1131
6687	SPG7	P10T-E	Human	Esophagus	ESCC	1.12e-35	6.01e-01	0.116
6687	SPG7	P11T-E	Human	Esophagus	ESCC	4.22e-19	8.09e-01	0.1426

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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:000683920	Esophagus	HGIN	mitochondrial transport	74/2587	254/18723	1.32e-10	1.32e-08	74
GO:000700618	Esophagus	HGIN	mitochondrial membrane organization	37/2587	116/18723	4.61e-07	2.07e-05	37
GO:005160417	Esophagus	HGIN	protein maturation	68/2587	294/18723	9.77e-06	2.86e-04	68
GO:003070517	Esophagus	HGIN	cytoskeleton-dependent intracellular transport	45/2587	195/18723	3.07e-04	5.15e-03	45
GO:00164857	Esophagus	HGIN	protein processing	49/2587	225/18723	7.04e-04	9.52e-03	49
GO:00109707	Esophagus	HGIN	transport along microtubule	35/2587	155/18723	2.01e-03	2.12e-02	35
GO:00469029	Esophagus	HGIN	regulation of mitochondrial membrane permeability	17/2587	63/18723	4.29e-03	3.82e-02	17
GO:19026869	Esophagus	HGIN	mitochondrial outer membrane permeabilization involved in programmed cell death	12/2587	40/18723	6.22e-03	4.95e-02	12
GO:0006839110	Esophagus	ESCC	mitochondrial transport	187/8552	254/18723	8.35e-20	9.81e-18	187
GO:000700619	Esophagus	ESCC	mitochondrial membrane organization	93/8552	116/18723	2.16e-14	1.11e-12	93
GO:005160418	Esophagus	ESCC	protein maturation	189/8552	294/18723	7.64e-11	2.39e-09	189
GO:003070518	Esophagus	ESCC	cytoskeleton-dependent intracellular transport	133/8552	195/18723	1.48e-10	4.27e-09	133
GO:001097013	Esophagus	ESCC	transport along microtubule	107/8552	155/18723	3.17e-09	6.80e-08	107
GO:000808810	Esophagus	ESCC	axo-dendritic transport	58/8552	75/18723	2.09e-08	4.02e-07	58
GO:004690217	Esophagus	ESCC	regulation of mitochondrial membrane permeability	49/8552	63/18723	1.91e-07	2.97e-06	49
GO:00905599	Esophagus	ESCC	regulation of membrane permeability	58/8552	78/18723	2.38e-07	3.61e-06	58
GO:00357948	Esophagus	ESCC	positive regulation of mitochondrial membrane permeability	36/8552	43/18723	2.90e-07	4.20e-06	36
GO:00989304	Esophagus	ESCC	axonal transport	49/8552	64/18723	4.54e-07	6.15e-06	49
GO:190268614	Esophagus	ESCC	mitochondrial outer membrane permeabilization involved in programmed cell death	33/8552	40/18723	1.80e-06	2.11e-05	33
GO:19057108	Esophagus	ESCC	positive regulation of membrane permeability	37/8552	48/18723	8.99e-06	8.65e-05	37

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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

SPG7

SNV

Missense_Mutation

novel

c.367N>A

p.Glu123Lys

p.E123K

Q9UQ90

protein_coding

tolerated(0.33)

benign(0.024)

TCGA-AC-A6IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPG7

SNV

Missense_Mutation

novel

c.2233N>A

p.Ala745Thr

p.A745T

Q9UQ90

protein_coding

tolerated(0.29)

possibly_damaging(0.491)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPG7

SNV

Missense_Mutation

novel

c.1553N>T

p.Gly518Val

p.G518V

Q9UQ90

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SPG7

SNV

Missense_Mutation

novel

c.877N>A

p.Ala293Thr

p.A293T

Q9UQ90

protein_coding

deleterious(0.01)

possibly_damaging(0.677)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SPG7

insertion

Nonsense_Mutation

novel

c.359_360insCTA

p.Ala120_Pro121insTer

p.A120_P121ins*

Q9UQ90

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPG7

insertion

Frame_Shift_Ins

novel

c.360_361insAACT

p.Pro121AsnfsTer3

p.P121Nfs*3

Q9UQ90

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPG7

insertion

In_Frame_Ins

novel

c.698_699insCCTGCTCCTCACTGAAGTGACCTCAGCGAATGAAGTGTG

p.Leu233_Asn234insLeuLeuLeuThrGluValThrSerAlaAsnGluValTrp

p.L233_N234insLLLTEVTSANEVW

Q9UQ90

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SPG7

insertion

Frame_Shift_Ins

novel

c.1431_1432insCCCTCAGCCTCCTCAGAGCGTTCAAGGTCCTGTCCTAAGAACATGG

p.Asp478ProfsTer28

p.D478Pfs*28

Q9UQ90

protein_coding

TCGA-BH-A0B4-01

Breast

breast invasive carcinoma

Male

>=65

III/IV

Hormone Therapy

tamoxiphen

SPG7

insertion

Frame_Shift_Ins

rs760818649

c.1053dupC

p.Gly352ArgfsTer44

p.G352Rfs*44

Q9UQ90

protein_coding

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPG7

SNV

Missense_Mutation

novel

c.953N>G

p.Lys318Arg

p.K318R

Q9UQ90

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C5-A2M2-01

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
6687	SPG7	PROTEASE, ENZYME		docetaxel	DOCETAXEL	20038957
6687	SPG7	PROTEASE, ENZYME		anthracyclines and related substances		23441093,21900104
6687	SPG7	PROTEASE, ENZYME		thalidomide	THALIDOMIDE	20038957

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