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: ACIN1

Gene summary for ACIN1

Gene summary.

Gene information	Species	Human
	Gene symbol	ACIN1
	Gene ID	22985
	Gene name	apoptotic chromatin condensation inducer 1
	Gene Alias	ACINUS
	Cytomap	14q11.2
	Gene Type	protein-coding
	GO ID	GO:0002262
	UniProtAcc	Q9UKV3

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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
22985	ACIN1	HTA11_1938_2000001011	Human	Colorectum	AD	1.36e-03	3.62e-01	-0.0811
22985	ACIN1	HTA11_347_2000001011	Human	Colorectum	AD	2.83e-03	3.11e-01	-0.1954
22985	ACIN1	HTA11_1391_2000001011	Human	Colorectum	AD	4.42e-03	4.28e-01	-0.059
22985	ACIN1	HTA11_866_3004761011	Human	Colorectum	AD	5.40e-04	3.74e-01	0.096
22985	ACIN1	HTA11_7696_3000711011	Human	Colorectum	AD	2.59e-02	3.95e-01	0.0674
22985	ACIN1	HTA11_99999965104_69814	Human	Colorectum	MSS	2.47e-02	4.32e-01	0.281
22985	ACIN1	A015-C-203	Human	Colorectum	FAP	2.73e-25	1.41e-01	-0.1294
22985	ACIN1	A015-C-204	Human	Colorectum	FAP	1.71e-02	-2.13e-02	-0.0228
22985	ACIN1	A002-C-201	Human	Colorectum	FAP	2.05e-06	7.62e-02	0.0324
22985	ACIN1	A001-C-119	Human	Colorectum	FAP	1.30e-07	4.42e-01	-0.1557
22985	ACIN1	A001-C-108	Human	Colorectum	FAP	2.31e-14	2.30e-01	-0.0272
22985	ACIN1	A002-C-021	Human	Colorectum	FAP	3.66e-05	3.93e-01	0.1171
22985	ACIN1	A002-C-205	Human	Colorectum	FAP	4.30e-20	3.34e-01	-0.1236
22985	ACIN1	A001-C-104	Human	Colorectum	FAP	6.52e-06	3.10e-01	0.0184
22985	ACIN1	A015-C-006	Human	Colorectum	FAP	2.47e-11	1.79e-01	-0.0994
22985	ACIN1	A015-C-106	Human	Colorectum	FAP	2.33e-06	1.96e-01	-0.0511
22985	ACIN1	A002-C-114	Human	Colorectum	FAP	7.36e-14	2.14e-01	-0.1561
22985	ACIN1	A015-C-104	Human	Colorectum	FAP	1.67e-30	3.08e-01	-0.1899
22985	ACIN1	A001-C-014	Human	Colorectum	FAP	9.22e-07	2.65e-02	0.0135
22985	ACIN1	A002-C-016	Human	Colorectum	FAP	1.86e-14	-1.63e-01	0.0521

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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
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
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:00027616	Oral cavity	OSCC	regulation of myeloid leukocyte differentiation	61/7305	120/18723	5.52e-03	2.14e-02	61
GO:19021075	Oral cavity	OSCC	positive regulation of leukocyte differentiation	77/7305	157/18723	6.55e-03	2.43e-02	77
GO:19037085	Oral cavity	OSCC	positive regulation of hemopoiesis	77/7305	157/18723	6.55e-03	2.43e-02	77
GO:000838025	Oral cavity	EOLP	RNA splicing	115/2218	434/18723	2.24e-17	3.04e-14	115
GO:003009926	Oral cavity	EOLP	myeloid cell differentiation	91/2218	381/18723	2.87e-11	4.15e-09	91
GO:000226226	Oral cavity	EOLP	myeloid cell homeostasis	49/2218	157/18723	7.93e-11	9.51e-09	49
GO:190370624	Oral cavity	EOLP	regulation of hemopoiesis	85/2218	367/18723	6.61e-10	5.06e-08	85
GO:004887226	Oral cavity	EOLP	homeostasis of number of cells	68/2218	272/18723	1.20e-09	8.27e-08	68
GO:003410126	Oral cavity	EOLP	erythrocyte homeostasis	41/2218	129/18723	1.48e-09	9.76e-08	41
GO:002241121	Oral cavity	EOLP	cellular component disassembly	94/2218	443/18723	1.00e-08	4.89e-07	94
GO:003021825	Oral cavity	EOLP	erythrocyte differentiation	37/2218	120/18723	2.29e-08	9.66e-07	37
GO:190313114	Oral cavity	EOLP	mononuclear cell differentiation	88/2218	426/18723	1.07e-07	3.61e-06	88
GO:0045637110	Oral cavity	EOLP	regulation of myeloid cell differentiation	51/2218	210/18723	3.63e-07	1.05e-05	51
GO:190210514	Oral cavity	EOLP	regulation of leukocyte differentiation	62/2218	279/18723	6.18e-07	1.60e-05	62
GO:000257323	Oral cavity	EOLP	myeloid leukocyte differentiation	48/2218	208/18723	3.71e-06	7.88e-05	48
GO:004563916	Oral cavity	EOLP	positive regulation of myeloid cell differentiation	26/2218	103/18723	1.28e-04	1.41e-03	26
GO:190210713	Oral cavity	EOLP	positive regulation of leukocyte differentiation	34/2218	157/18723	3.32e-04	3.08e-03	34
GO:190370813	Oral cavity	EOLP	positive regulation of hemopoiesis	34/2218	157/18723	3.32e-04	3.08e-03	34
GO:000276114	Oral cavity	EOLP	regulation of myeloid leukocyte differentiation	26/2218	120/18723	1.57e-03	1.05e-02	26
GO:003022415	Oral cavity	EOLP	monocyte differentiation	10/2218	36/18723	7.42e-03	3.58e-02	10

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa03040	Colorectum	AD	Spliceosome	73/2092	217/8465	1.73e-03	9.68e-03	6.18e-03	73
hsa03015	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030401	Colorectum	AD	Spliceosome	73/2092	217/8465	1.73e-03	9.68e-03	6.18e-03	73
hsa030151	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030402	Colorectum	MSS	Spliceosome	66/1875	217/8465	2.58e-03	1.27e-02	7.81e-03	66
hsa030403	Colorectum	MSS	Spliceosome	66/1875	217/8465	2.58e-03	1.27e-02	7.81e-03	66
hsa030152	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030153	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa0304018	Esophagus	HGIN	Spliceosome	79/1383	217/8465	3.22e-13	7.00e-12	5.56e-12	79
hsa030159	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa030137	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa0304019	Esophagus	HGIN	Spliceosome	79/1383	217/8465	3.22e-13	7.00e-12	5.56e-12	79
hsa0301514	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa0301312	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa030407	Liver	Cirrhotic	Spliceosome	102/2530	217/8465	5.69e-08	9.47e-07	5.84e-07	102
hsa030154	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0304012	Liver	Cirrhotic	Spliceosome	102/2530	217/8465	5.69e-08	9.47e-07	5.84e-07	102
hsa0301511	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66

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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

ACIN1

SNV

Missense_Mutation

c.1982C>G

p.Ser661Cys

p.S661C

Q9UKV3

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.987)

TCGA-5L-AAT0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ACIN1

SNV

Missense_Mutation

c.2549N>A

p.Arg850His

p.R850H

Q9UKV3

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ACIN1

SNV

Missense_Mutation

novel

c.253G>A

p.Glu85Lys

p.E85K

Q9UKV3

protein_coding

deleterious_low_confidence(0.04)

probably_damaging(0.996)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ACIN1

SNV

Missense_Mutation

rs201004575

c.2135N>T

p.Pro712Leu

p.P712L

Q9UKV3

protein_coding

deleterious_low_confidence(0)

benign(0.122)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ACIN1

SNV

Missense_Mutation

c.1775G>T

p.Arg592Ile

p.R592I

Q9UKV3

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.974)

TCGA-C8-A26X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

ACIN1

SNV

Missense_Mutation

rs768412898

c.529G>A

p.Glu177Lys

p.E177K

Q9UKV3

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.931)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

ACIN1

SNV

Missense_Mutation

novel

c.119N>T

p.Arg40Leu

p.R40L

Q9UKV3

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.995)

TCGA-GI-A2C8-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

Adriamycin

ACIN1

insertion

Nonsense_Mutation

novel

c.1161_1162insCCCTACACAGAGATGGAGGATTAAGCAAGATCTTC

p.Ser388ProfsTer8

p.S388Pfs*8

Q9UKV3

protein_coding

TCGA-A8-A079-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

ACIN1

insertion

Nonsense_Mutation

novel

c.1869_1870insTTTCCCTAGTTCCCTAGTTACTACCTGTCATTAAGCTA

p.Arg624PhefsTer3

p.R624Ffs*3

Q9UKV3

protein_coding

TCGA-A8-A07I-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

ACIN1

insertion

Nonsense_Mutation

novel

c.3123_3124insATCTGACCGCCTTGGCCTCCCAAAGTGCTGGGATTACAGGCGTGA

p.Glu1041_Ala1042insIleTerProProTrpProProLysValLeuGlyLeuGlnAlaTer

p.E1041_A1042insI*PPWPPKVLGLQA*

Q9UKV3

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

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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