POM121 overexpression is related to a poor prognosis in colorectal cancer

Figures & data

Figure 1. POM121 mRNA expression in CRC tissues and normal colorectal tissues. qRT-PCR demonstrated that the levels of POM121 mRNA in the 29 CRC samples (T)were higher than those in normal colorectal samples (N) (**p < 0.001).

Figure 2. IHC staining for POM121 expression in colorectal samples. (a),(b)Positive IHC staining of POM121 in well-differentiated adenocarcinoma. (c), (d)Positive IHC staining of POM121 in moderately differentiated adenocarcinoma. (e), (f)Positive IHC staining of POM121 in poorly-differentiated adenocarcinoma.(g), (h) Negative IHC staining of POM121 in normal colorectal tissue. (Original images×4, scale bars500 μm; enlarged images×40, scale bars 50 μm).

Table 1. POM121 expression in colorectal tissues.

		POM121 expression(%)
Characteristic	n	Low or no	High	χ^2	Bonferroni P-value
colonitis	78	59 (75.64)	19 (24.36)	104.542	0.000*
carcinoma	581	194 (33.39)	37 (66.61)
Pericarcinomatous	112	85 (75.89)	27 (24.11)

POM121 protein expression incolonitis, carcinoma and pericarcinomatous tissue were detected by immunohistochemical staining. *According to the Bonferroni correction, there was a significant difference between the three groups: p < 0.0167.

Table 2. POM121 expression level and CRC patients’ clinicopathological characteristics.

		POM121 expression (%)
Characteristics	n	Low or no	High	Pearson χ^2	Bonferroni P-value
Total	581	194 (33.39)	387 (66.61)
Gender				0.546	0.460
Male	420	144 (34.29)	276 (65.71)
Female	161	50 (31.06)	111 (68.94)
Age				0.118	0.732
<60	213	73 (34.27)	140 (65.73)
≥60	368	121 (32.88)	247 (67.12)
location				2.885	0.410
Right	126	42 (33.33)	84 (66.67)
Transverse	96	32 (33.33)	64 (66.67)
Left	148	42 (28.38)	106 (71.62)
Sigmoid	211	78 (36.97)	133 (63.03)
Histological type				1.117	0.291
Adenocarcinoma	509	166 (32.61)	343 (67.39)
Mucinous/SRCC^a	72	28 (38.89)	44 (61.11)
Differentiation				1.838	0.399
Well	162	61 (37.65)	101 (62.35)
Moderate	223	71 (31.84)	152 (68.16)
Poor	196	62 (31.63)	134 (68.37)
Tumor size				5.9379	0.115
T1	18	4 (22.22)	14 (77.78)
T2	82	36 (43.90)	46 (56.10)
T3	347	108 (31.12)	239 (68.88)
T4	134	46 (34.33)	88 (65.67)
Lymph node metastasis				13.2883	0.001*
N0	255	95 (37.25)	160 (62.75)
N1	193	72 (37.31)	121 (62.69)
N2	133	27 (20.30)	106 (79.70)
Distant metastasis				8.987	0.003*
M0	490	176 (35.92)	314 (64.08)
M1	91	18 (19.78)	73 (80.22)
AJCC stage				10.289	0.006*
Ⅰ	138	59 (42.75)	79 (57.25)
Ⅱ	289	96 (33.22)	193 (66.78)
Ⅲ	105	25 (23.81)	80 (76.19)
Ⅳ	49	14 (28.57)	35 (71.43)
Venous invasion				3.877	0.049*
Negative	501	175 (34.93)	326 (65.07)
Positive	80	19 (23.75)	61 (76.25)
Perineural invasion				40.581	0.000*
Negative	495	191(38.59)	304 (61.41)
Positive	86	3 (3.49)	83 (96.51)
Preoperative CEA,ng/ml				26.916	0.000*
<5	254	108 (42.52)	146 (57.48)
≥5	288	67 (23.26)	221 (76.74)
Unknown	39	19 (48.72)	20 (51.28)
Preoperative CA199,ng/ml				14.010	0.001*
≤37	251	98 (39.04)	153 (60.96)
>37	291	77 (26.46)	214 (73.54)
Unknown	39	19 (48.72)	20 (51.28)
Ki67				32.348	0.000*
Negative	180	90 (50.00)	90 (50.00)
Positive	401	104 (25.94)	297 (74.06)

* According to the Bonferroni correction, we adjusted the p-value and set a significant difference between the two groups: p < 0.05; there was a significant difference between the three groups: p < 0.0167; there was significant difference between the four groups: p < 0.0083.

a: Mucinous carcinoma is 57 cases; SRCC (signet-ring cell carcinoma) is 15 cases.

b: No clear differentiation stage diagnosis.

Figure 3. Survival curves of CRC patients using Kaplan-Meier plots. (a) Overall survival rates in patients with low POM121 expression(blue line)and high POM121 expression (green line).(b) Overall survival rates of patients in TNM 0 + I(blue line), TNMII(green line), TNM III (gray line)and TNM IV (purple line).(c) Overall survival rates in patients with positive venous invasion (blue line) and negative venous invasion (green line). (d) Overall survival curves by distant metastases: M0 (blue line) and M1 (green line).

Table 3. Univariate and multivariable analysis of prognostic factors for overall survival in CRC.

	Univariate analysis			Multivariate analysis
	HR	P -value	95CI	HR	P-value	95%CI
POM121 expression
High vs Low or no	1.005	0.000*	1.004 1.007	1.005	0.000*	1.003 1.006
Age(year)
<60 vs ≥60	1.406	0.003*	1.120 1.766	1.228	0.128	0.943 1.598
Gender
Male vs Female	1.154	0.223	0.916 1.453
Tumor size
High vs Low or no	1.055	0.439	0.922 1.207
Lymph node metastasis
N0 vs N1 + N2	1.021	0.759	0.893 1.167
Distant metastasis
M0 vs M1	5.367	0.000*	4.142 6.905	5.472	0.000*	4.416 7.191
TNM stage
I + II vs III + IV	1.136	0.040*	1.006 1.283	1.915	0.009*	1.811 3.032
Venous invasion
Negative vs Positive	1.242	0.002*	1.083 1.423	1.188	0.436	0.770 1.832
Ki67
High vs Low or no	1.240	0.000*	1.128 1.363	1.076	0.642	0.790 1.466

*P < 0.05

HR: Hazard ratio; CI: Confidence interval.

Figure 4. The main enriched KEGG pathways and the protein interaction network. (a)Gene expression levels in patients with high and low POM121expressionwere compared through GSEA. Gene sets involved in the cell cycle, spliceosome, basal transcription factors, DNA replication, mismatch repair and base excision repair were enriched in the POM121-high expression phonotype. (b) MYC, CCNA1, and44 other proteins were confirmed to interact with POM121. (c) MYC andCCNA1 showed a significant relationship with POM121 expression in CRC.

Table 4. Enriched pathways for differential expression POM121 in CRC.

KEGG pathway	ES	NES	Normal p-value	FDR q-value
spliceosome	0.47	1.96	0.006	0.050
nucleotide excision repair	0.67	1.95	0.000	0.033
basal transcription factors	0.55	1.77	0.010	0.108
DNA replication	0.73	1.76	0.002	0.095
cell cycle	0.57	1.74	0.002	0.086
homologous recombination	0.69	1.73	0.010	0.079
mismatch repair	0.65	1.72	0.008	0.067
base excision repair	0.54	1.71	0.012	0.063
ubiquitin mediated proteolysis	0.38	1.58	0.022	0.163

ES: enrichment score; NES: normal enrichment score; FDR: false discovery rate; FWER: family wise error rate.