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: IGHA1

Gene summary for IGHA1

Gene summary.

Gene information	Species	Human
	Gene symbol	IGHA1
	Gene ID	3493
	Gene name	immunoglobulin heavy constant alpha 1
	Gene Alias	IgA1
	Cytomap	14q32.33
	Gene Type	other
	GO ID	GO:0001775
	UniProtAcc	NA

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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
3493	IGHA1	CA_HPV_1	Human	Cervix	CC	1.35e-66	-1.51e+00	0.0264
3493	IGHA1	CA_HPV_2	Human	Cervix	CC	6.59e-80	-1.60e+00	0.0391
3493	IGHA1	CA_HPV_3	Human	Cervix	CC	5.86e-60	-1.53e+00	0.0414
3493	IGHA1	HSIL_HPV_1	Human	Cervix	HSIL_HPV	2.77e-32	-1.23e+00	0.0116
3493	IGHA1	HSIL_HPV_2	Human	Cervix	HSIL_HPV	3.23e-31	-9.70e-01	0.0208
3493	IGHA1	N_HPV_1	Human	Cervix	N_HPV	2.25e-16	-7.67e-01	0.0079
3493	IGHA1	N_HPV_2	Human	Cervix	N_HPV	3.98e-78	-1.59e+00	-0.0131
3493	IGHA1	CCI_1	Human	Cervix	CC	4.05e-30	-1.66e+00	0.528
3493	IGHA1	CCI_2	Human	Cervix	CC	4.11e-28	-1.66e+00	0.5249
3493	IGHA1	CCI_3	Human	Cervix	CC	4.38e-38	-1.66e+00	0.516
3493	IGHA1	CCII_1	Human	Cervix	CC	5.65e-50	-1.66e+00	0.3249
3493	IGHA1	Tumor	Human	Cervix	CC	1.01e-90	-1.66e+00	0.1241
3493	IGHA1	sample1	Human	Cervix	CC	4.98e-43	-1.66e+00	0.0959
3493	IGHA1	sample3	Human	Cervix	CC	1.69e-85	-1.65e+00	0.1387
3493	IGHA1	H2	Human	Cervix	HSIL_HPV	5.44e-66	-1.47e+00	0.0632
3493	IGHA1	L1	Human	Cervix	CC	9.32e-46	-1.60e+00	0.0802
3493	IGHA1	T1	Human	Cervix	CC	1.50e-77	-1.61e+00	0.0918
3493	IGHA1	T2	Human	Cervix	CC	1.72e-17	-1.37e+00	0.0709
3493	IGHA1	T3	Human	Cervix	CC	2.92e-80	-1.63e+00	0.1389
3493	IGHA1	HTA11_2951_2000001011	Human	Colorectum	AD	6.26e-26	1.49e+00	0.0216

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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
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
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
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:00027644	Cervix	CC	immune response-regulating signaling pathway	97/2311	468/18723	1.49e-07	7.07e-06	97
GO:00018949	Cervix	CC	tissue homeostasis	57/2311	268/18723	2.43e-05	4.21e-04	57
GO:00602498	Cervix	CC	anatomical structure homeostasis	63/2311	314/18723	6.03e-05	8.68e-04	63
GO:00457306	Cervix	CC	respiratory burst	14/2311	37/18723	6.97e-05	9.81e-04	14
GO:00022533	Cervix	CC	activation of immune response	72/2311	375/18723	8.26e-05	1.11e-03	72
GO:0002768	Cervix	CC	immune response-regulating cell surface receptor signaling pathway	59/2311	315/18723	6.64e-04	6.11e-03	59
GO:00026967	Cervix	CC	positive regulation of leukocyte activation	72/2311	409/18723	1.13e-03	9.31e-03	72
GO:00512516	Cervix	CC	positive regulation of lymphocyte activation	65/2311	362/18723	1.15e-03	9.39e-03	65
GO:00508676	Cervix	CC	positive regulation of cell activation	73/2311	420/18723	1.50e-03	1.16e-02	73
GO:00197308	Cervix	CC	antimicrobial humoral response	27/2311	122/18723	1.70e-03	1.29e-02	27
GO:00602634	Cervix	CC	regulation of respiratory burst	7/2311	17/18723	2.72e-03	1.85e-02	7
GO:00018957	Cervix	CC	retina homeostasis	19/2311	79/18723	2.94e-03	1.94e-02	19
GO:00024603	Cervix	CC	adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	62/2311	356/18723	3.09e-03	2.03e-02	62
GO:0002443	Cervix	CC	leukocyte mediated immunity	73/2311	440/18723	5.01e-03	2.98e-02	73
GO:0006909	Cervix	CC	phagocytosis	53/2311	308/18723	7.49e-03	4.01e-02	53
GO:00069597	Cervix	CC	humoral immune response	54/2311	317/18723	8.57e-03	4.42e-02	54
GO:00103243	Cervix	CC	membrane invagination	28/2311	144/18723	9.50e-03	4.72e-02	28
GO:000695912	Cervix	HSIL_HPV	humoral immune response	39/737	317/18723	2.88e-10	7.02e-08	39
GO:000269611	Cervix	HSIL_HPV	positive regulation of leukocyte activation	44/737	409/18723	1.58e-09	3.04e-07	44
GO:005086711	Cervix	HSIL_HPV	positive regulation of cell activation	44/737	420/18723	3.59e-09	5.76e-07	44

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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

IGHA1

SNV

Missense_Mutation

rs587723177

c.820N>A

p.Glu274Lys

p.E274K

P01876

IG_C_gene

tolerated(0.19)

benign(0.276)

TCGA-BH-A0W4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

IGHA1

SNV

Missense_Mutation

rs771398040

c.403N>A

p.Glu135Lys

p.E135K

P01876

IG_C_gene

deleterious(0.01)

probably_damaging(0.984)

TCGA-C8-A130-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

IGHA1

SNV

Missense_Mutation

rs768421910

c.419N>A

p.Gly140Asp

p.G140D

P01876

IG_C_gene

tolerated(0.07)

possibly_damaging(0.575)

TCGA-E2-A14S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

IGHA1

SNV

Missense_Mutation

novel

c.390C>A

p.His130Gln

p.H130Q

P01876

IG_C_gene

tolerated(0.8)

benign(0.006)

TCGA-E9-A228-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

IGHA1

SNV

Missense_Mutation

novel

c.859N>A

p.Gln287Lys

p.Q287K

P01876

IG_C_gene

tolerated(0.12)

benign(0.17)

TCGA-LL-A5YP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

IGHA1

SNV

Missense_Mutation

rs1128904

c.361N>C

p.Ser121Pro

p.S121P

P01876

IG_C_gene

tolerated(0.33)

benign(0)

TCGA-DS-A1OA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

IGHA1

SNV

Missense_Mutation

novel

c.808N>A

p.Glu270Lys

p.E270K

P01876

IG_C_gene

tolerated(0.1)

possibly_damaging(0.498)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IGHA1

SNV

Missense_Mutation

novel

c.972C>A

p.Phe324Leu

p.F324L

P01876

IG_C_gene

deleterious(0)

probably_damaging(0.999)

TCGA-JW-A69B-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IGHA1

SNV

Missense_Mutation

novel

c.1042N>A

p.Val348Met

p.V348M

P01876

IG_C_gene

deleterious(0.04)

possibly_damaging(0.617)

TCGA-UC-A7PG-06

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

IGHA1

SNV

Missense_Mutation

rs587723177

c.820G>A

p.Glu274Lys

p.E274K

P01876

IG_C_gene

tolerated(0.19)

benign(0.276)

TCGA-AZ-4313-01

Colorectum

colon adenocarcinoma

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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