Bioinformatics analysis of insulin-like growth factor 2-binding protein 2 in predicting prognosis of oral cancer

doi:10.3877/cma.j.issn.1674-1366.2025.02.002

Abstract

Abstract:

Objective

To investigate the role of insulin-like growth factor 2-binding protein 2（IGF2BP2），an important effector of N⁶-methyladenosine（m⁶A），in the development and progression of oral cancer.

Methods

The transcriptome data and clinical information related to oral cancer were selected from the cancer genome atlas（TCGA）and gene expression omnibus（GEO）databases from 2012-2024.Genome enrichment analysis（GSEA），Kyoto Encyclopedia of Genes and Genomes（KEGG）analysis，gene ontology（GO）analysis，correlation analysis，and Cox regression analysis were performed on the data using the R package.Pathological sections of oral cancer were obtained from Xiangya Stomatology Hospital，Central South University.The expression level of IGF2BP2 was verified by immunohistochemistry and immunofluorescence analysis，and the results were statistically analyzed based on t test.

Results

The dysregulation of m⁶A-related protein played an important role in the development of tumors.It was found that the higher the expression of the m⁶A-related molecule IGF2BP2，the lower the overall survival rate of patients with oral cancer（P＜0.05）.IGF2BP2 was the most upregulated m⁶A-related protein in oral cancer（P＜0.001），and the ROC curve showed that the coefficient of IGF2BP2 in predicting oral cancer was 0.839.Immunohistochemical and immunofluorescence analysis showed that the expression of IGF2BP2 in oral cancer was significantly higher than that in the normal oral tissues（P＜0.05）.High expression of IGF2BP2 was positively correlated with high grade（P＜0.05），stage（P＜0.05），and primary site（P＜0.05）of oral cancer.Univariate（P＜0.05）and multivariate（P=0.074）regression analysis showed that IGF2BP2 had independent prognostic value in oral cancer.GSEA，KEGG，GO，and correlation analysis further demonstrated that upregulated IGF2BP2 affected immunity by altering the distribution of macrophage M0 and regulatory T cells（Tregs）and interacting with immune checkpoint genes，thereby affecting the efficacy of immunotherapy.

Conclusions

Upregulated IGF2BP2 was positively correlated with higher tumor stage and poorer prognosis of oral cancer.IGF2BP2 played an important role in the occurrence and development of oral cancer.

Key words: Oral cancers, N⁶-methyladenosine, Insulin-like growth factor 2 binding protein 2, Prognosis, Immunotherapy

Xiangzhu Wang, Yuelin Ma, Xiaoli Xie, Haiye Jiang. Bioinformatics analysis of insulin-like growth factor 2-binding protein 2 in predicting prognosis of oral cancer[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2025, 19(02): 84-95.

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References 35

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临床特征	口腔癌组（n =320）	正常对照组（n =49）	检验值	P 值
平均年龄（IQR）	62（53，71）	61（54，67）	t =0.53	0.60^a
性别［例（%）］			χ ² =0.21	0.65^b
女性	107（33.43）	18（36.73）
男性	213（66.57）	31（63.27）
原发肿瘤灶［例（%）］			F =11.01	0.09^b
口腔	73（22.81）	16（32.65）
舌头	133（41.56）	26（53.06）
颊黏膜	23（7.19）	0
唇	3（0.94）	0
牙槽嵴	18（5.63）	0
硬腭	7（2.19）	1（2.04）
口底	63（19.69）	6（12.24）
饮酒［例（%）］			χ ² =0.46	0.50^b
是	206（63.70）	29（59.18）
否	114（36.30）	20（40.82）
肿瘤分级［例（%）］			-	-
T1	19（5.94）	-
T2	101（31.56）	-
T3	79（24.69）	-
T4	113（35.31）	-
TX	8（2.50）	-
淋巴结状态［例（%）］			-	-
N0	166（51.88）	-
N1 ～ N3	142（44.37）	-
NX	12（3.75）	-
肿瘤分期［例（%）］			-	-
Ⅰ	12（3.75）	-
Ⅱ	77（24.06）	-
Ⅲ	66（20.63）	-
Ⅳ	157（49.06）	-
X	8（2.50）	-

临床特征	口腔癌组（n =320）	正常对照组（n =49）	检验值	P 值
平均年龄（IQR）	62（53，71）	61（54，67）	t =0.53	0.60^a
性别［例（%）］			χ ² =0.21	0.65^b
女性	107（33.43）	18（36.73）
男性	213（66.57）	31（63.27）
原发肿瘤灶［例（%）］			F =11.01	0.09^b
口腔	73（22.81）	16（32.65）
舌头	133（41.56）	26（53.06）
颊黏膜	23（7.19）	0
唇	3（0.94）	0
牙槽嵴	18（5.63）	0
硬腭	7（2.19）	1（2.04）
口底	63（19.69）	6（12.24）
饮酒［例（%）］			χ ² =0.46	0.50^b
是	206（63.70）	29（59.18）
否	114（36.30）	20（40.82）
肿瘤分级［例（%）］			-	-
T1	19（5.94）	-
T2	101（31.56）	-
T3	79（24.69）	-
T4	113（35.31）	-
TX	8（2.50）	-
淋巴结状态［例（%）］			-	-
N0	166（51.88）	-
N1 ～ N3	142（44.37）	-
NX	12（3.75）	-
肿瘤分期［例（%）］			-	-
Ⅰ	12（3.75）	-
Ⅱ	77（24.06）	-
Ⅲ	66（20.63）	-
Ⅳ	157（49.06）	-
X	8（2.50）	-

基因	免疫检查点基因	相关系数r 值	P 值
IGF2BP2	ADORA2A	-0.19	＜0.001
IGF2BP2	TNFRSF14	-0.22	＜0.001
IGF2BP2	IDO2	-0.32	＜0.001
IGF2BP2	CD276	0.35	＜0.001
IGF2BP2	CD48	-0.28	＜0.001
IGF2BP2	ICOSLG	-0.22	＜0.001
IGF2BP2	CD27	-0.31	＜0.001
IGF2BP2	CD40LG	-0.34	＜0.001
IGF2BP2	TIGIT	-0.22	＜0.001
IGF2BP2	BTLA	-0.29	＜0.001
IGF2BP2	CD44	0.52	＜0.001
IGF2BP2	CD28	-0.21	＜0.001
IGF2BP2	TNFRSF9	-0.19	＜0.001
IGF2BP2	TNFSF9	0.18	＜0.001
IGF2BP2	CD200R1	-0.20	＜0.001
IGF2BP2	CD244	-0.26	＜0.001
IGF2BP2	LGALS9	-0.21	＜0.001
IGF2BP2	NRP1	0.21	＜0.001
IGF2BP2	PDCD1	-0.22	＜0.001
IGF2BP2	TMIGD2	-0.25	＜0.001
IGF2BP2	HHLA2	0.18	＜0.001

基因	免疫检查点基因	相关系数r 值	P 值
IGF2BP2	ADORA2A	-0.19	＜0.001
IGF2BP2	TNFRSF14	-0.22	＜0.001
IGF2BP2	IDO2	-0.32	＜0.001
IGF2BP2	CD276	0.35	＜0.001
IGF2BP2	CD48	-0.28	＜0.001
IGF2BP2	ICOSLG	-0.22	＜0.001
IGF2BP2	CD27	-0.31	＜0.001
IGF2BP2	CD40LG	-0.34	＜0.001
IGF2BP2	TIGIT	-0.22	＜0.001
IGF2BP2	BTLA	-0.29	＜0.001
IGF2BP2	CD44	0.52	＜0.001
IGF2BP2	CD28	-0.21	＜0.001
IGF2BP2	TNFRSF9	-0.19	＜0.001
IGF2BP2	TNFSF9	0.18	＜0.001
IGF2BP2	CD200R1	-0.20	＜0.001
IGF2BP2	CD244	-0.26	＜0.001
IGF2BP2	LGALS9	-0.21	＜0.001
IGF2BP2	NRP1	0.21	＜0.001
IGF2BP2	PDCD1	-0.22	＜0.001
IGF2BP2	TMIGD2	-0.25	＜0.001
IGF2BP2	HHLA2	0.18	＜0.001

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