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: C2

Gene summary for C2

Gene summary.

Gene information	Species	Human
	Gene symbol	C2
	Gene ID	717
	Gene name	complement C2
	Gene Alias	ARMD14
	Cytomap	6p21.33
	Gene Type	protein-coding
	GO ID	GO:0002250
	UniProtAcc	P06681

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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
717	C2	HTA11_866_3004761011	Human	Colorectum	AD	9.60e-11	3.26e-01	0.096
717	C2	HTA11_99999970781_79442	Human	Colorectum	MSS	3.85e-17	5.04e-01	0.294
717	C2	HTA11_99999965062_69753	Human	Colorectum	MSI-H	6.80e-09	1.08e+00	0.3487
717	C2	HTA11_99999965104_69814	Human	Colorectum	MSS	2.21e-24	1.13e+00	0.281
717	C2	HTA11_99999973899_84307	Human	Colorectum	MSS	1.55e-14	6.46e-01	0.2585
717	C2	HTA11_99999974143_84620	Human	Colorectum	MSS	6.66e-14	4.41e-01	0.3005
717	C2	HCC1_Meng	Human	Liver	HCC	5.21e-104	9.88e-01	0.0246
717	C2	cirrhotic3	Human	Liver	Cirrhotic	3.95e-06	1.72e-01	0.0215
717	C2	HCC1	Human	Liver	HCC	2.70e-35	4.32e+00	0.5336
717	C2	HCC2	Human	Liver	HCC	8.30e-50	5.44e+00	0.5341
717	C2	HCC5	Human	Liver	HCC	6.08e-08	3.29e+00	0.4932
717	C2	Pt13.a	Human	Liver	HCC	5.10e-26	6.25e-01	0.021
717	C2	Pt13.b	Human	Liver	HCC	1.22e-38	6.06e-01	0.0251
717	C2	Pt13.c	Human	Liver	HCC	2.61e-20	8.58e-01	0.0076
717	C2	Pt14.a	Human	Liver	HCC	4.55e-04	3.22e-01	0.0169
717	C2	Pt14.b	Human	Liver	HCC	1.11e-07	3.28e-01	0.018
717	C2	Pt14.d	Human	Liver	HCC	5.54e-12	3.82e-01	0.0143
717	C2	S014	Human	Liver	HCC	6.48e-32	1.31e+00	0.2254
717	C2	S015	Human	Liver	HCC	3.75e-26	1.44e+00	0.2375
717	C2	S016	Human	Liver	HCC	7.07e-26	1.07e+00	0.2243

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:00061199	Breast	Precancer	oxidative phosphorylation	53/1080	141/18723	1.15e-29	2.04e-26	53
GO:00090608	Breast	Precancer	aerobic respiration	58/1080	189/18723	5.69e-27	7.62e-24	58
GO:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00453338	Breast	Precancer	cellular respiration	59/1080	230/18723	5.97e-23	5.32e-20	59
GO:00159808	Breast	Precancer	energy derivation by oxidation of organic compounds	70/1080	318/18723	8.33e-23	6.37e-20	70
GO:00196468	Breast	Precancer	aerobic electron transport chain	34/1080	87/18723	3.95e-20	2.64e-17	34
GO:00427738	Breast	Precancer	ATP synthesis coupled electron transport	35/1080	95/18723	1.08e-19	5.76e-17	35
GO:00427758	Breast	Precancer	mitochondrial ATP synthesis coupled electron transport	35/1080	95/18723	1.08e-19	5.76e-17	35
GO:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:00229048	Breast	Precancer	respiratory electron transport chain	35/1080	114/18723	8.51e-17	3.26e-14	35
GO:20012429	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway	41/1080	164/18723	6.48e-16	2.31e-13	41
GO:00229008	Breast	Precancer	electron transport chain	42/1080	175/18723	1.37e-15	4.59e-13	42
GO:19026008	Breast	Precancer	proton transmembrane transport	39/1080	157/18723	4.18e-15	1.18e-12	39
GO:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00159857	Breast	Precancer	energy coupled proton transport, down electrochemical gradient	16/1080	26/18723	4.15e-14	9.65e-12	16
GO:00159867	Breast	Precancer	ATP synthesis coupled proton transport	16/1080	26/18723	4.15e-14	9.65e-12	16
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa051714	Colorectum	MSS	Coronavirus disease - COVID-19	108/1875	232/8465	6.50e-17	1.67e-15	1.03e-15	108
hsa051715	Colorectum	MSS	Coronavirus disease - COVID-19	108/1875	232/8465	6.50e-17	1.67e-15	1.03e-15	108
hsa051716	Colorectum	MSI-H	Coronavirus disease - COVID-19	91/797	232/8465	2.21e-35	3.58e-33	3.00e-33	91
hsa051717	Colorectum	MSI-H	Coronavirus disease - COVID-19	91/797	232/8465	2.21e-35	3.58e-33	3.00e-33	91
hsa0517122	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
hsa046102	Liver	Cirrhotic	Complement and coagulation cascades	48/2530	86/8465	4.41e-07	5.44e-06	3.35e-06	48
hsa05133	Liver	Cirrhotic	Pertussis	37/2530	76/8465	4.17e-04	2.57e-03	1.58e-03	37
hsa04936	Liver	Cirrhotic	Alcoholic liver disease	60/2530	142/8465	1.07e-03	5.85e-03	3.61e-03	60
hsa0517132	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
hsa046103	Liver	Cirrhotic	Complement and coagulation cascades	48/2530	86/8465	4.41e-07	5.44e-06	3.35e-06	48
hsa051331	Liver	Cirrhotic	Pertussis	37/2530	76/8465	4.17e-04	2.57e-03	1.58e-03	37
hsa049361	Liver	Cirrhotic	Alcoholic liver disease	60/2530	142/8465	1.07e-03	5.85e-03	3.61e-03	60
hsa0517142	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167
hsa049362	Liver	HCC	Alcoholic liver disease	89/4020	142/8465	1.73e-04	8.53e-04	4.75e-04	89
hsa046104	Liver	HCC	Complement and coagulation cascades	57/4020	86/8465	3.19e-04	1.45e-03	8.04e-04	57
hsa051332	Liver	HCC	Pertussis	48/4020	76/8465	4.17e-03	1.27e-02	7.06e-03	48
hsa0517152	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167
hsa049363	Liver	HCC	Alcoholic liver disease	89/4020	142/8465	1.73e-04	8.53e-04	4.75e-04	89
hsa046105	Liver	HCC	Complement and coagulation cascades	57/4020	86/8465	3.19e-04	1.45e-03	8.04e-04	57
hsa051333	Liver	HCC	Pertussis	48/4020	76/8465	4.17e-03	1.27e-02	7.06e-03	48

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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
HLA-E	KLRC2	HLA-E_KLRC2	MHC-I	Breast	ADJ
ANGPTL4	SDC2	ANGPTL4_SDC2	ANGPTL	Breast	ADJ
MDK	SDC2	MDK_SDC2	MK	Breast	ADJ
MDK	SDC2	MDK_SDC2	MK	Breast	DCIS
PTN	SDC2	PTN_SDC2	PTN	Breast	DCIS
ANGPTL4	SDC2	ANGPTL4_SDC2	ANGPTL	Breast	DCIS
MDK	SDC2	MDK_SDC2	MK	Breast	Healthy
ANGPTL4	SDC2	ANGPTL4_SDC2	ANGPTL	Breast	Healthy
PTN	SDC2	PTN_SDC2	PTN	Breast	Healthy
HLA-E	KLRC2	HLA-E_KLRC2	MHC-I	Breast	IDC
MDK	SDC2	MDK_SDC2	MK	Breast	IDC
ANGPTL4	SDC2	ANGPTL4_SDC2	ANGPTL	Breast	IDC
ANGPTL4	SDC2	ANGPTL4_SDC2	ANGPTL	Breast	Precancer
MDK	SDC2	MDK_SDC2	MK	Breast	Precancer
HLA-E	KLRC2	HLA-E_KLRC2	MHC-I	Cervix	ADJ
MDK	SDC2	MDK_SDC2	MK	Cervix	ADJ
PTN	SDC2	PTN_SDC2	PTN	Cervix	ADJ
HLA-E	KLRC2	HLA-E_KLRC2	MHC-I	Cervix	CC
MDK	SDC2	MDK_SDC2	MK	Cervix	CC
PTN	SDC2	PTN_SDC2	PTN	Cervix	CC

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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

SNV

Missense_Mutation

novel

c.1050N>A

p.Met350Ile

p.M350I

P06681

protein_coding

tolerated(0.19)

possibly_damaging(0.511)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SNV

Missense_Mutation

c.346G>A

p.Glu116Lys

p.E116K

P06681

protein_coding

tolerated(0.06)

benign(0.215)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

novel

c.803N>G

p.Asn268Ser

p.N268S

P06681

protein_coding

tolerated(0.77)

benign(0)

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SNV

Missense_Mutation

rs567227615

c.256N>T

p.Pro86Ser

p.P86S

P06681

protein_coding

tolerated(0.13)

benign(0.028)

TCGA-BH-A18Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SNV

Missense_Mutation

rs764034564

c.185N>A

p.Arg62Gln

p.R62Q

P06681

protein_coding

deleterious(0.02)

benign(0.366)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

insertion

Frame_Shift_Ins

novel

c.2056_2057insCATGTCTGGCTAATTTTTGTATTTTT

p.Glu686AlafsTer21

p.E686Afs*21

P06681

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

deletion

Frame_Shift_Del

novel

c.729_739delNNNNNNNNNNN

p.Lys244ProfsTer22

p.K244Pfs*22

P06681

protein_coding

TCGA-BH-A1F6-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SNV

Missense_Mutation

rs766407308

c.394C>T

p.Arg132Cys

p.R132C

P06681

protein_coding

deleterious(0.02)

benign(0.012)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SNV

Missense_Mutation

c.1315N>G

p.Leu439Val

p.L439V

P06681

protein_coding

tolerated(0.43)

benign(0.26)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

SNV

Missense_Mutation

c.811C>G

p.Leu271Val

p.L271V

P06681

protein_coding

tolerated(0.24)

benign(0)

TCGA-LP-A4AV-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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