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: SEC16B

Gene summary for SEC16B

Gene summary.

Gene information	Species	Human
	Gene symbol	SEC16B
	Gene ID	89866
	Gene name	SEC16 homolog B, endoplasmic reticulum export factor
	Gene Alias	LZTR2
	Cytomap	1q25.2
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q96JE7

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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
89866	SEC16B	NAFLD1	Human	Liver	NAFLD	2.38e-08	7.62e-01	-0.04
89866	SEC16B	S43	Human	Liver	Cirrhotic	7.63e-07	-1.51e-01	-0.0187
89866	SEC16B	HCC1_Meng	Human	Liver	HCC	1.79e-40	-9.42e-02	0.0246
89866	SEC16B	HCC2_Meng	Human	Liver	HCC	2.47e-10	-5.03e-02	0.0107
89866	SEC16B	cirrhotic1	Human	Liver	Cirrhotic	5.38e-04	-1.68e-01	0.0202
89866	SEC16B	Pt13.a	Human	Liver	HCC	2.26e-04	-1.54e-01	0.021
89866	SEC16B	S028	Human	Liver	HCC	6.16e-06	3.94e-01	0.2503
89866	SEC16B	S029	Human	Liver	HCC	8.21e-10	7.85e-01	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:00481936	Liver	NAFLD	Golgi vesicle transport	66/1882	296/18723	3.66e-10	9.30e-08	66
GO:0007030	Liver	NAFLD	Golgi organization	36/1882	157/18723	1.76e-06	7.68e-05	36
GO:00512227	Liver	NAFLD	positive regulation of protein transport	55/1882	303/18723	1.07e-05	3.35e-04	55
GO:19049517	Liver	NAFLD	positive regulation of establishment of protein localization	55/1882	319/18723	4.79e-05	1.14e-03	55
GO:00068885	Liver	NAFLD	endoplasmic reticulum to Golgi vesicle-mediated transport	26/1882	130/18723	4.78e-04	6.78e-03	26
GO:00903166	Liver	NAFLD	positive regulation of intracellular protein transport	29/1882	160/18723	1.24e-03	1.41e-02	29
GO:00325273	Liver	NAFLD	protein exit from endoplasmic reticulum	12/1882	48/18723	2.30e-03	2.19e-02	12
GO:00331576	Liver	NAFLD	regulation of intracellular protein transport	37/1882	229/18723	2.55e-03	2.36e-02	37
GO:0070861	Liver	NAFLD	regulation of protein exit from endoplasmic reticulum	8/1882	27/18723	3.97e-03	3.34e-02	8
GO:00323866	Liver	NAFLD	regulation of intracellular transport	49/1882	337/18723	5.34e-03	4.11e-02	49
GO:00323886	Liver	NAFLD	positive regulation of intracellular transport	32/1882	202/18723	6.42e-03	4.69e-02	32
GO:004819311	Liver	Cirrhotic	Golgi vesicle transport	153/4634	296/18723	1.02e-23	6.43e-21	153
GO:000688811	Liver	Cirrhotic	endoplasmic reticulum to Golgi vesicle-mediated transport	77/4634	130/18723	5.78e-17	7.56e-15	77
GO:003238611	Liver	Cirrhotic	regulation of intracellular transport	147/4634	337/18723	1.84e-14	1.72e-12	147
GO:003315711	Liver	Cirrhotic	regulation of intracellular protein transport	108/4634	229/18723	1.23e-13	1.04e-11	108
GO:190495112	Liver	Cirrhotic	positive regulation of establishment of protein localization	135/4634	319/18723	3.20e-12	2.28e-10	135
GO:00709724	Liver	Cirrhotic	protein localization to endoplasmic reticulum	45/4634	74/18723	4.79e-11	2.73e-09	45
GO:005122212	Liver	Cirrhotic	positive regulation of protein transport	126/4634	303/18723	6.85e-11	3.77e-09	126
GO:003238811	Liver	Cirrhotic	positive regulation of intracellular transport	92/4634	202/18723	8.60e-11	4.66e-09	92
GO:009031611	Liver	Cirrhotic	positive regulation of intracellular protein transport	77/4634	160/18723	1.17e-10	6.21e-09	77

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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

SEC16B

SNV

Missense_Mutation

novel

c.1458N>C

p.Met486Ile

p.M486I

Q96JE7

protein_coding

deleterious(0.04)

possibly_damaging(0.525)

TCGA-A7-A26H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

SEC16B

SNV

Missense_Mutation

rs12074076

c.2180C>T

p.Ser727Leu

p.S727L

Q96JE7

protein_coding

tolerated(0.27)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC16B

SNV

Missense_Mutation

novel

c.1128G>T

p.Gln376His

p.Q376H

Q96JE7

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC16B

SNV

Missense_Mutation

rs12074076

c.2180C>T

p.Ser727Leu

p.S727L

Q96JE7

protein_coding

tolerated(0.27)

benign(0)

TCGA-BH-A203-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC16B

SNV

Missense_Mutation

c.883N>T

p.Pro295Ser

p.P295S

Q96JE7

protein_coding

deleterious(0.04)

probably_damaging(0.995)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

SEC16B

SNV

Missense_Mutation

novel

c.2932N>A

p.Gly978Ser

p.G978S

Q96JE7

protein_coding

deleterious(0.05)

benign(0.43)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

SEC16B

SNV

Missense_Mutation

novel

c.3055N>T

p.Pro1019Ser

p.P1019S

Q96JE7

protein_coding

tolerated(0.07)

probably_damaging(0.996)

TCGA-D8-A73U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SEC16B

SNV

Missense_Mutation

c.2189G>A

p.Gly730Glu

p.G730E

Q96JE7

protein_coding

tolerated(1)

benign(0.001)

TCGA-E2-A1B1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Other, specify in notesbiphosphonate

zoledronic

SEC16B

SNV

Missense_Mutation

rs777631840

c.3160N>T

p.Arg1054Cys

p.R1054C

Q96JE7

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-E2-A1LG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SEC16B

SNV

Missense_Mutation

c.953N>A

p.Ser318Tyr

p.S318Y

Q96JE7

protein_coding

deleterious(0.01)

possibly_damaging(0.492)

TCGA-E9-A295-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

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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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