Does the Autophagy Related Gene 7 (ATG7) Have a Role in Non-Melanoma Skin Cancer?

Figures & data

Table 1 Demographic and Clinical Data of the SCC and BCC

Item	SCC (n=27), n (%)	BCC (n=77), n (%)
Age (years)
X±SD	54.2±20.3	59.7±18.2
Median	54	60
Range	6–77	15–90
Gender
Male	15 (55.6)	35 (45.5)
Female	12 (44.4)	42 (54.5)
Localization
Head and neck	18 (66.7)	65 (84.4)
Trunk	6 (22.2)	12 (15.6)
Extremities	3 (11.1)	0 (0)
Clinical presentation
Ulcer	10 (37)	43 (55.8)
Mass	17 (63)	34 (44.2)
Margin
Not assessed	6 (22.2)	29 (37.7)
Not involved	19 (70.4)	44 (57.1)
Involved	2 (7.4)	4 (5.2)
Size
Mean±SD	3.7±3.4	3.2±2.5
Min–Max	0.5–15	0.2–12
Median	2.5 (2–3.5)	3 (1.9–4)
LVI
Present	0 (0)	0 (0)
Absent	27 (100)	77 (100)
Perineural invasion
Present	0 (0)	0 (0)
Absent	27 (100)	77 (100)

Abbreviations: LVI, lymphovascular invasion; n, number; X, mean; SD, standard deviation.

Figure 1 A case of SCC. (A) Moderate-to-strong nucleocytoplasmic expression of ATG7 both in tumor and the surrounding stoma. (B) High power view of previous case. (C) Mild-to-moderate nucleocytoplasmic immunohistochemical expression of ATG7 in sebaceous gland (ATG7 IHC ×200 for A and C and ×400 for B).

Figure 2 A case of BCC. (A) Strong nucleocytoplasmic expression of ATG7 both in tumor and surrounding stroma. (B) High power view of previous case. (C) Strong immunohistochemical expression of ATG7 in cut section of hair follicle (ATG7 IHC ×200 for A and B and ×400 for C).

Figure 3 Normal skin. (A) Epidermis showed mild to moderate cytoplasmic expression of ATG7. (B) Dermis showed mild nucleocytoplasmic expression of ATG7 in hair follicle and eccrine sweat glands (ATG7 IHC ×200 for A and B).

Table 2 Comparison Between Studied Groups Regarding ATG7 Expressions

Epithelium	BCC (n=77)	SCC (n=27)	Control (n=20)	Test	P-value
	n (%)	n (%)	n (%)
Epithelium
Status
Positive	77 (100)	27 (100)	20 (100)	NA	—
Negative	0 (0)	0 (0.0)	0 (0)
Localization
Cytoplasmic	0 (0)	0 (0)	11 (55)	χ^2=62.8	<0.001
Nucleocytoplasmic	77 (100)	27 (100)	9 (45)
H score
X±SD	251.7±43.2	207.04±44.6	85±32.2	K=61.8	<0.001
Median	260	200	80
Range	140 – 300	120 – 300	30 – 130
H groups
Low	2 (2.6)	2 (7.4)	20 (100)	χ^2=99.7	<0.001
High	75 (97.4)	25 (92.6)	0 (0)
Stroma
Status
Positive	77 (100)	27 (100)	20 (100)	NA	—
Negative	0 (0)	0 (0.0)	0 (0)
Localization
Cytoplasmic	0 (0)	0 (0)	10 (50)	χ^2=56.6	<0.001
Nucleocytoplasmic	77 (100)	27 (100)	10 (50)
H-score
X±SD	234.3±55.6	169.4±54	49±27.7	K=64.9	<0.001
Median	250	160	45
Range	60–300	80–300	10–100
H groups
Low	6 (7.8)	7 (25.9)	20 (100)	χ^2=69.1	<0.001
High	71 (92.2)	20 (74.1)	0 (0)

Abbreviations: X, mean; SD, standard deviation; K, Kruskal Wallis test; n, number; χ², chi-square test; NA, not applicable.

Table 3 Relation Between ATG7 H Score and Clinical Parameters of the Patients

Items H Score	All Patients (n=104) Mean±SD	Test of Sig.	P-value
Epithelium
Localization
Head and neck	242.8±45.5	Kruskal Wallis=4.5	0.11
Trunk	236.7±55.5
Extremities	183.3±15.3
Clinical presentation
Ulcer	243.6±46.7	Mann Whitney=0.71	0.48
Mass	236.3±48.7
Margin
Not assessed	232.1±9.1	Kruskal Walis=3.2	0.20
Not involved	246.8±42.4
Involved	213.3±51.6
Size	r=0.17	P=0.08
Stroma
Localization
Head and neck	220.6±62.1	Kruskal Wallis=3.4	0.19
Trunk	211.7±63.5
Extremities	165±13.2
Clinical presentation
Ulcer	220.8±54.3	Mann Whitney=0.29	0.77
Mass	214.1±69.3
Margin
Not assessed	215.6±67.4	Kruskal Wallis=0.96	0.62
Not involved	220.6±58.9
Involved	195±64.7
Size	r=0.12	P=0.21

Note: r, correlation coefficient.

Abbreviations: Sig., significant; SD, standard deviation.

Table 4 Relationship Between ATG7 H Score (Epithelial and Stromal) and Clinical Parameters in SCC Patients

Items	SCC Epithelial H Score Mean±SD	SCC Stromal H Score Mean±SD	Test of Sig.	P-value
Localization
Head and neck	212.8±38.2	172.2±52.1	F=0.59*	P1=0.56
Trunk	236.7±55.5	163.3±76.1	Kruskal Wallis=0.59**	P2=0.81
Extremities	183.3±15.3	165±13.2
Clinical presentation
Ulcer	215±36.3	178±44.4	Mann Whitney=0.88*	P1=0.38
Mass	202.4±49.3	164.4±59.6	t=0.62**	P2=0.53
Margin
Not assessed	185±21.7	150±28.4	F=1.4*	P1=0.26
Not involved	216.3±49.1	177.9±60.5	F=0.78**	P2=0.47
Involved	185±21.2	145±35.4
Size	r=−0.09		P1=0.64 P2=0.64
Staging group
I (11)	206.4±13.7	180.9±64.7	F=0.07*	P1=0.93
II (12)	210±49.5	50.8±37.8	F=1.4**	P2=0.26
III (4)	200±35.6	193.8±58.5

Notes: F, one way Anova test; r, correlation coefficient; t, Student’s test; P1, relationship between epithelial H score and clinical parameters; P2, relationship between stromal H score and clinical parameters; *significance between SCC epithelial H score and clinical parameters; **significance between SCC stromal H score and clinical parameters.

Abbreviation: SD, standard deviation.

Table 5 Relationship Between ATG7 H Score (Epithelial and Stromal) and Clinical Parameters in BCC Patients

Items	BCC Epithelial H Score Mean±SD	BCC Stromal H Score Mean±SD	Test of Sig.	P-value
Localization
Head and neck	251.1±44.1	234±58.1	Mann Whitney=0.007*	P1=0.99 (>0.05)
Trunk	254.2±39.6	235.8±41	Mann Whitney=0.33**	P2=0.74 (>0.05)
Clinical presentation
Ulcer	250.2±46.7	230.7±51.9	Mann Whitney=0.05*	P1=0.96 (>0.05)
Mass	253.2±38.9	238.8±60.4	Mann Whitney=1.04**	P2=0.29 (>0.05)
Margin
Not assessed	242.1±53.7	228.9±65.4	Kruskal Wallis=1.7*	P1=0.42
Not involved	260±31.5	239.1±48.2	Kruskal Wallis=0.42**	P2=0.81
Involved	227.5±59.1	220±63.8
Size	r=0.25	r=0.16	P1=0.027 P2=0.16

Notes: r, correlation coefficient; P1, relationship between BCC epithelial H score and clinical parameters; P2, relationship between BCC stromal H score and clinical parameters; *significance between BCC epithelial H score and clinical parameters; **significance between BCC stromal H score and clinical parameters.

Abbreviation: SD, standard deviation.

Figure 4 (A) A significant positive correlation between H score (epithelial & stromal) of ATG7 in all patients (r=+0.48, P=0.00). (B) A significant positive correlation between H score (epithelial & stromal) of ATG7 in BCC patients (r=+0.29, P=0.009). (C) A significant positive correlation between H score (epithelial & stromal) of ATG7 in SCC patients (r=+0.61, P=0.00).

Notes: “r” describes the direction of correlation as either positive or negative, otherwise P-value shows a statistically significant correlation between studied groups. *Significant P-value; **highly significant P-value.