The Relationship Between UBE2C and AGGF1 Overexpression and Tumor Angiogenesis in Non-Small Cell Lung Cancer

Figures & data

Table 1 Patients Characteristics

Patients Characteristics	Frequency (n)	Percentage (%)
Age (years)
<60	51	33.1
≥60	103	66.9
Gender
Female	50	32.5
Male	104	67.5
Smoking
No	88	57.1
Yes	66	42.9
Tumor size (cm)
≤3	77	50.0
> 3	77	50.0
Gross Type
Central	87	56.5
Peripheral	67	43.5
Histologic Type
SCC	76	49.4
Ade	78	50.6
Grade
Well	28	18.2
Moderate	85	55.2
Poor	41	26.6
LNM
No	71	46.1
Yes	83	53.9
TNM stage
I+II	93	60.4
III+IV	61	39.6

Abbreviations: SCC, squamous cell carcinoma; Ade, adenocarcinoma; LNM, lymph node metastasis; TNM, tumor-node-metastasis.

Table 2 The Correlation Between UBE2C, or AGGF1, or VM, or MVD and Clinicopathological Characteristics in NSCLC

Variables	UBE2C			AGGF1			VM				MVD
	Negative	Positive	P	Negative	Positive	P	Negative	Positive	P		Low	High	P
Age (years)			0.323			0.593			0.219				0.152
<60	19	32		19	32		29	22			25	26
≥60	47	56		43	60		69	34			63	40
Gender			0.842			0.272			0.515				0.112
Female	22	28		17	33		30	20			24	26
Male	44	60		45	59		68	36			64	40
Smoking			0.925			0.420			0.310				0.452
No	38	50		33	55		53	35			48	40
Yes	28	38		29	37		45	21			40	26
Gross Type			0.925			0.734			0.117				0.083
Central	37	50		34	53		60	27			55	32
Peripheral	29	38		28	39		38	29			33	34
Histologic Type			0.609			0.263			0.059				0.245
SCC	31	45		34	42		54	22			47	29
Ade	35	43		28	50		44	34			41	37
Grade			0.420			0.791			0.385				0.172
Well	13	15		10	18		21	7			20	8
Moderate	39	46		34	51		52	33			48	37
Poor	14	27		18	23		25	16			20	21
Tumor size (cm)			0.003^a			0.009^a			0.003^a				0.009^a
≤3	42	35		23	54		58	19			52	25
> 3	24	53		39	38		40	37			36	41
LNM			0.005^a			0.002^a			<0.001^b				0.002^a
No	39	32		38	33		59	12			50	21
Yes	27	56		24	59		39	44			38	45
TNM stage			0.001^a			0.028^a			0.001^a				0.009^a
I+II	50	43		44	49		69	24			61	32
III+IV	16	45		18	43		29	32			27	34

Note: ^aP < 0.05; ^bP < 0.001.

Abbreviations: NSCLC, non-small cell lung cancer; SCC, squamous cell carcinoma; Ade, adenocarcinoma; LNM, lymph node metastasis; TNM, tumor-node-metastasis; VM, vasculogenic mimicry; AGGF1, angiogenic factor with G patch and FHA domains 1; UBE2C, ubiquitin-conjugating enzyme E2C; MVD, the microvessel density.

Figure 1 Immunostaining of UBE2C, AGGF1, VM and MVD in NSCLC and control tissues. (A) Positive staining of UBE2C in NSCLC tissues (×400). (B) Negative staining of UBE2C in control tissues (×400). (C) Positive staining of AGGF1 in NSCLC tissues (×400). (D) Negative staining of AGGF1 in control tissues (×400). (E) Positive staining of VM in NSCLC tissues (×400). (F) Negative staining of VM in control tissues (×400). (G) High MVD in NSCLC tissues (×400). (H) Low MVD in control tissues (×400).

Abbreviations: NSCLC, non-small cell lung cancer; UBE2C, ubiquitin-conjugating enzyme E2C; AGGF1, angiogenic factor with Gpatch and FHA domains 1; VM, vasculogenic mimicry; MVD, the microvessel density.

Table 3 Correlation Among UBE2C, AGGF1, VM, and MVD in NSCLC

Variables	UBE2C				AGGF1				VM
	Negative	Positive	r	P	Negative	Positive	r	P	Negative	Positive	r	P
MVD			0.485	<0.001^b			0.363	<0.001^b			0.682	<0.001^b
Low	56	32			49	39			81	7
High	10	56			13	53			17	49
UBE2C							0.226	0.005^a			0.518	<0.001^b
Negative					35	31			61	5
Positive					27	61			37	51
AGGF1											0.318	<0.001^b
Negative									51	11
Positive									47	45

Notes: ^aP < 0.05; ^bP < 0.001.

Abbreviations: VM, vasculogenic mimicry; AGGF1, angiogenic factor with G patch and FHA domains 1; UBE2C, ubiquitin-conjugating enzyme E2C; MVD, the microvessel density.

Figure 2 Kaplan-Meier analysis of OS in NSCLC patients. (A) Correlation between OS and UBE2C (χ² = 49.521, P < 0.001). (B) Correlation between OS and AGGF1 (χ² = 23.383, P < 0.001). (C) Correlation between OS and VM (χ² = 86.409, P < 0.001). (D) Correlation between OS and MVD (χ² = 73.650, P < 0.001). (E) Correlation between OS and LNM (χ² = 43.688, P < 0.001). (F) Correlation between OS and TNM stage (χ² = 53.170, P < 0.001).

Abbreviations: NSCLC, non-small cell lung cancer; UBE2C, ubiquitin-conjugating enzyme E2C; AGGF1, angiogenic factor with Gpatch and FHA domains 1; VM, vasculogenic mimicry; MVD, the microvessel density; OS, overall survival; LNM, lymph node metastasis; TNM, tumor-node-metastasis.

Figure 3 Kaplan-Meier analysis of DFS in NSCLC patients. (A) Correlation between DFS and UBE2C (χ² = 46.156, P < 0.001). (B) Correlation between DFS and AGGF1 (χ² = 20.113, P < 0.001). (C) Correlation between DFS and VM (χ² = 86.340, P < 0.001). (D) Correlation between DFS and MVD (χ² = 69.609, P < 0.001). (E) Correlation between DFS and LNM (χ² = 44.624, P < 0.001). (F) Correlation between DFS and TNM stage (χ² = 53.613, P < 0.001).

Abbreviations: NSCLC, non-small cell lung cancer; UBE2C, ubiquitin-conjugating enzyme E2C; AGGF1, angiogenic factor with Gpatch and FHA domains 1; VM, vasculogenic mimicry; MVD, the microvessel density; DFS, disease-free survival; LNM, lymph node metastasis; TNM, tumor-node-metastasis.

Table 4 Univariate and Multivariate Analysis of OS and Clinicopathological Variables

Variables	Number	Univariable Analysis		Multivariable Analysis
		HR (95% CI)	P	HR (95% CI)	P
UBE2C		4.059(2.676–6.158)	<0.001^b	1.946(1.202–3.150)	0.007^a
Negative	66
Positive	88
AGGF1		2.582(1.728–3.858)	<0.001^b	1.909(1.195–3.051)	0.007^a
Negative	62
Positive	92
VM		5.773(3.833–8.696)	<0.001^b	2.107(1.226–3.622)	0.007^a
Negative	98
Positive	56
MVD		5.124(3.408–7.704)	<0.001^b	2.490(1.473–4.210)	0.001^a
Low	88
High	66
Age (years)		0.739(0.502–1.088)	0.125	–	–
<60	51
≥60	103
Gender		1.214(0.823–1.791)	0.328	–	–
Female	50
Male	104
Smoking		1.074(0.740–1.558)	0.707	–	–
No	88
Yes	66
Gross Type		0.850(0.583–1.240)	0.399	–	–
Central	87
Peripheral	67
Histologic Type		1.033(0.713–1.497)	0.863	–	–
SCC	76
Ade	78
Grade		1.173(0.887–1.552)	0.263	–	–
Well	28
Moderate	85
Poor	41
Tumor size (cm)		1.690(1.165–2.451)	0.006^a	1.670(1.075–2.594)	0.023^a
≤3	77
> 3	77
LNM		3.593(2.398–5.383)	<0.001^b	1.846(1.162–2.934)	0.009^a
No	71
Yes	83
TNM stage		3.888(2.629–5.748)	<0.001^b	2.837(1.845–4.363)	<0.001^b
I+II	93
III+IV	61

Notes: ^aP < 0.05; ^bP < 0.001.

Abbreviations: SCC, squamous cell carcinoma; Ade, adenocarcinoma; LNM, lymph node metastasis; TNM, tumor-node-metastasis; VM, vasculogenic mimicry; AGGF1, angiogenic factor with G patch and FHA domains 1; UBE2C, ubiquitin-conjugating enzyme E2C; MVD, the microvessel density; OS, overall survival.

Table 5 Univariate and Multivariate Analysis of DFS and Clinicopathological Variables

Variables	Number	Univariable Analysis		Multivariable Analysis
		HR (95% CI)	P	HR (95% CI)	P
UBE2C		3.853(2.549–5.822)	<0.001^b	1.812(1.118–2.935)	0.016^a
Negative	66
Positive	88
AGGF1		2.388(1.609–3.546)	<0.001^b	1.778(1.116–2.835)	0.016^a
Negative	62
Positive	92
VM		5.802(3.848–8.747)	<0.001^b	2.286(1.333–3.920)	0.003^a
Negative	98
Positive	56
MVD		4.906(3.269–7.363)	<0.001^b	2.376(1.421–3.972)	0.001^a
Low	88
High	66
Age (years)		0.758(0.516–1.115)	0.160	–	–
<60	51
≥60	103
Gender		1.215(0.824–1.790)	0.326	–	–
Female	50
Male	104
Smoking		1.149(0.794–1.662)	0.462	–	–
No	88
Yes	66
Gross Type		0.843(0.579–1.228)	0.374	–	–
Central	87
Peripheral	67
Histologic Type		1.002(0.693–1.448)	0.992	–	–
SCC	76
Ade	78
Grade		1.165(0.882–1.539)	0.281	–	–
Well	28
Moderate	85
Poor	41
Tumor size (cm)		1.678(1.159–2.430)	0.006^a	1.666(1.073–2.588)	0.023^a
≤3	77
> 3	77
LNM		3.660(2.440–5.488)	<0.001^b	1.948(1.224–3.100)	0.005^a
No	71
Yes	83
TNM stage		3.934(2.657–5.825)	<0.001^b	2.800(1.822–4.301)	<0.001^b
I+II	93
III+IV	61

Notes: ^aP < 0.05; ^bP < 0.001.

Abbreviations: SCC, squamous cell carcinoma; Ade, adenocarcinoma; LNM, lymph node metastasis; TNM, tumor-node-metastasis; VM, vasculogenic mimicry; AGGF1, angiogenic factor with G patch and FHA domains 1; UBE2C, ubiquitin-conjugating enzyme E2C; MVD, the microvessel density; DFS, disease-free survival.