Predictive and prognostic implications of 4E-BP1, Beclin-1, and LC3 for cetuximab treatment combined with chemotherapy in advanced colorectal cancer with wild-type KRAS: Analysis from real-world data

Table 1 Correlations of Beclin1, LC3, and 4E-BP1 expression with clinicopathological characteristics in 68 advanced colorectal cancer patients n (%)

Variable	n = 68	Beclin1 expression			LC3 expression			4E-BP1 expression
		Low	High	P-value	Low	High	P-value	Low	High	P-value
Sex				0.061			0.372			0.571
Male	44 (64.7)	13	24		12	25		8	28
Female	24 (35.3)	2	17		4	15		3	16
Age (yr)				0.119			0.167			0.865
< 65	55 (80.9)	10	35		11	34		9	35
≥ 65	13 (19.1)	5	6		5	6		2	9
Family history of cancer				0.593			0.151			0.382
Yes	13 (19.1)	2	8		1	9		1	9
No	55 (80.9)	13	33		15	31		10	35
Location1				0.862			1.000			0.634
Left	50 (73.5)	11	31		12	30		2	33
Right	18 (26.5)	4	10		4	10		9	11
Pathological grade				0.349			0.349	8		0.897
1 + 2	44 (64.7)	8	30		8	30		8	29
3	18 (26.4)	5	10		5	10		3	12
NA	6 (8.9)
T stage				0.618			0.618			0.911
T1 + T2 + T3	41 (60.3)	9	24		9	24		6	26
T4	22 (32.4)	4	15		4	15		4	16
NA	5 (7.3)
N stage				0.058			0.058			0.654
No	22 (32.4)	6	9		6	9		4	12
N1 + N2	36 (52.9)	5	28		5	28		6	25
NA	10 (14.7)
Synchronous/metachronous metastasis				0.020			0.058			0.162
Synchronous metastasis	24 (35.3)	1	18		2	17		5	12
Metachronous metastasis	43 (63.2)	13	23		13	23		5	32
NA	1 (1.5)
KRAS				0.044			0.044			0.651
Wild type	45 (66.2)	13	24		13	24		7	30
Mutant type	10 (14.7)	0	9		0	9		2	6
NA	13 (19.1)

Location: The primary tumor location was classified as right-sided or left-sided according to the splenic flexure. CRC: Colorectal cancer; LC3: Microtubule-associated protein 1A/B-light chain 3; NA: Not applicable; 4E-BP1: 4E-binding protein 1.

Table 2 Relationships of Beclin1, LC3, and 4E-BP1 with short-term efficacy of first-line cetuximab-containing therapy in 25 patients with wild-type KRAS

Factor			DCR		ORR		PFS
		n (%)	n (%)	P-value	n (%)	P-value	Time (mo)	P-value
		25
Beclin1	High	12 (48.0)	7 (58.3)	0.325	5 (41.6)	1.000	8.80	0.843
	Low	8 (32.0)	7 (87.5)		4 (50.0)		4.70
	NA	5 (20.0)
LC3	High	12 (48.0)	7 (58.3)	0.325	4 (33.3)	0.362	4.70	0.167
	Low	8 (32.0)	7 (87.5)		5 (62.5)		9.96
	NA	5 (20.0)
4E-BP1	High	15 (60.0)	12 (80.0)	0.560	9 (60.0)	0.303	5.32	0.410
	Low	5 (20.0)	3 (60.0)		1 (20.0)		7.36
	NA	5 (20.0)

LC3: Microtubule-associated protein 1A/B-light chain 3; 4E-BP1: 4E-binding protein 1; NA: Not applicable; DCR: Disease control rate; ORR: Overall response rate; PFS: Primary-progression-free survival from the initiation of first-line treatment to tumor progression, death from any cause, or the last follow-up.

Table 3 Univariate and multivariate analyses of the influence of Beclin1, LC3, 4E-BP1, and clinicopathological factors on survival in 45 patients with wild-type KRAS who were treated with cetuximab

	OS
	Univariate analysis		Multivariate analysis
	HR (95%CI)	P-value	HR (95%CI)	P-value
Sex	0.860 (0.452, 1.636)	0.496
Age	2.050 (0.831, 5.056)	0.111
Family	1.568 (0.786, 3.128)	0.198
Tumor location	0.933 (0.463, 1.880)	0.353
Pathological grade	2.273 (1.549, 3.335)	0.000	2.421 (1.397, 4.197)	0.002
T stage	1.240 (0.977, 1.573)	0.072	1.749 (1.190, 2.569)	0.004
N stage	1.159 (0.611, 2.200)	0.409
Synchronous/metachronous metastasis	1.493 (0.793, 2.813)	0.081
Beclin1 expression	0.466 (0.223, 0.971)	0.037	0.209 (0.064, 0.685)	0.010
LC3 expression	0.541 (0.262, 1.122)	0.094
4E-BP1 expression	2.926 (1.110, 7.713)	0.024	6.385 (1.764, 23.112)	0.005

Bold values indicate P < 0.05; tumor location, left side or right side. CI: Confidence interval; CRC: Colorectal cancer; HR: Hazard ratio; LC3: Microtubule-associated protein 1A/B-light chain 3; 4E-BP1: 4E-binding protein 1.