Construction and validation of a risk model for colorectal cancer prognosis based on N6-methyladenosine modification and immune infiltration

YANG Jingjing; GUO Huaijuan; MAO Jingxian; WANG Jiaxin; WANG Ying; YAN Xuebing; PAN Xiaoping

doi:10.7619/jcmp.20240201

Journal of Clinical Medicine in Practice > 2024 > 28(7): 1-8. > DOI: 10.7619/jcmp.20240201

YANG Jingjing, GUO Huaijuan, MAO Jingxian, WANG Jiaxin, WANG Ying, YAN Xuebing, PAN Xiaoping. Construction and validation of a risk model for colorectal cancer prognosis based on N6-methyladenosine modification and immune infiltration[J]. Journal of Clinical Medicine in Practice, 2024, 28(7): 1-8. DOI: 10.7619/jcmp.20240201

Citation:

PDF (5432 KB)

Construction and validation of a risk model for colorectal cancer prognosis based on N6-methyladenosine modification and immune infiltration

1.
Department of Oncology, the Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, 225000
2.
Health Management Center, the Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, 225000

More Information

Received Date: January 10, 2024
Revised Date: March 10, 2024
Available Online: April 21, 2024

Graphical Abstract

Abstract

Abstract

Objective
To investigate the prognostic value of N6-methyladenosine (m⁶A) modification related genes and immune infiltration in colorectal cancer (CRC) and construct a risk model for predicting outcome of patients.
Methods
The transcriptome data and matched clinical information of CRC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The prognostic value of m⁶A modification related genes and immune infiltration were investigated using the consensus clustering method and single sample gene set enrichment analysis. The weighted gene co-expression network analysis (WGCNA) was used to identify prognostic genes related with m⁶A modification and immune infiltration. Lasso regression analysis was used to construct a multi-gene risk model. The expression differences of prognostic genes identified were further validated through expression differential analysis in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, the Kaplan-Meier was used to evaluate the predicting performance of the model in different subgroups and external validation cohorts.
Results
Both the m⁶A modification and immune infiltration phenotype could effectively stratify the prognosis of CRC patients from the TCGA cohort. Most m⁶A modification related genes were significantly correlated with immune infiltration in CRC tissues. Four following prognostic genes were selected using the WGCNA method combined with Lasso regression analysis: intelectin-1, lymphocyte antigen 6 complex locus G6D, atonal homolog 1 and matrix metalloproteinase 28. In colorectal cancer tissues, the expression levels of lymphocyte antigen 6 complex locus G6D and matrix metalloproteinase 28 exhibited significant differences compared to adjacent non-cancerous tissues (P < 0.05). The risk model constructed based on the above prognostic genes can effectively identify the potential risk population with poor prognosis in different clinical subgroups of the TCGA cohort and the GEO validated cohort.
Conclusion
A risk model based on m⁶A modification and immune infiltration could effectively predict the clinical outcome of CRC patients, and related prognostic genes have potential to be developed as molecular targets for CRC therapy.
- colorectal cancer,
- N6-methyladenosine modification,
- immune infiltration,
- biomarker,
- prognosis

FullText(HTML)

References (25)

References

[1]	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
[2]	JIANG X H, JIN Z Y, YANG Y Z, et al. m6A modification on the fate of colorectal cancer: functions and mechanisms of cell proliferation and tumorigenesis[J]. Front Oncol, 2023, 13: 1162300. doi: 10.3389/fonc.2023.1162300
[3]	胡茹, 李东霖, 严雪冰. 甲基转移酶样蛋白14与肿瘤[J]. 国际肿瘤学杂志, 2022, 49(8): 478-483. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYX202405003.htm
[4]	ELEMAM N M, TALAAT I M, ASSAL R A, et al. Editorial: understanding the crosstalk between immune cells and the tumor microenvironment in cancer and its implications for immunotherapy[J]. Front Med, 2023, 10: 1202581. doi: 10.3389/fmed.2023.1202581
[5]	ZHENG Z W, WIEDER T, MAUERER B, et al. T cells in colorectal cancer: unravelling the function of different T cell subsets in the tumor microenvironment[J]. Int J Mol Sci, 2023, 24(14): 11673. doi: 10.3390/ijms241411673
[6]	PERICLEOUS S, BHOGAL R H, MAVROEIDIS V K. The role of circulating biomarkers in the early detection of recurrent colorectal cancer following resection of liver metastases[J]. Front Biosci, 2022, 27(6): 189. doi: 10.31083/j.fbl2706189
[7]	任燕珍, 李蕊仙, 陈建娥, 等. 解偶联蛋白2的表达与结直肠癌患者临床病理特征和预后的关系[J]. 实用临床医药杂志, 2022, 26(23): 20-25. doi: 10.7619/jcmp.20222104
[8]	LIN Y, SHI H J, WU L P, et al. Research progress of N6-methyladenosine in colorectal cancer: a review[J]. Medicine, 2023, 102(47): e36394. doi: 10.1097/MD.0000000000036394
[9]	QU X, TAN H H, MAO J X, et al. Identification of a novel prognostic signature correlated with epithelial-mesenchymal transition, N6-methyladenosine modification, and immune infiltration in colorectal cancer[J]. Cancer Med, 2023, 12(5): 5926-5938. doi: 10.1002/cam4.5384
[10]	ZHANG Z, MEI Y, HOU M X. Knockdown RBM15 inhibits colorectal cancer cell proliferation and metastasis via N6-methyladenosine (m6A) modification of MyD88 mRNA[J]. Cancer Biother Radiopharm, 2022, 37(10): 976-986.
[11]	ZHANG Z, WANG L, ZHAO L, et al. N6-methyladenosine demethylase ALKBH5 suppresses colorectal cancer progression potentially by decreasing PHF20 mRNA methylation[J]. Clin Transl Med, 2022, 12(8): e940. doi: 10.1002/ctm2.940
[12]	LI M C, LIU Z H, HOU Z, et al. Oncogenic zinc finger protein ZNF687 accelerates lung adenocarcinoma cell proliferation and tumor progression by activating the PI3K/AKT signaling pathway[J]. Thorac Cancer, 2023, 14(14): 1223-1238. doi: 10.1111/1759-7714.14856
[13]	JIANG T, XING L S, ZHAO L P, et al. Comprehensive analysis of m6A related gene mutation characteristics and prognosis in colorectal cancer[J]. BMC Med Genomics, 2023, 16(1): 105. doi: 10.1186/s12920-023-01509-8
[14]	SUN C L, CHEN J, XING Z W, et al. METTL14 suppresses cancer stem cell phenotype of colorectal cancer via regulating of β-catenin/NANOG[J]. J Cancer, 2023, 14(8): 1407-1416. doi: 10.7150/jca.82158
[15]	XU Y Q, BAO Y X, QIU G Z, et al. METTL3 promotes proliferation and migration of colorectal cancer cells by increasing SNHG1 stability[J]. Mol Med Rep, 2023, 28(5): 217. doi: 10.3892/mmr.2023.13104
[16]	BEILMANN-LEHTONEN I, KASURINEN J, HAGSTRÖ M J, et al. High tissue expression of TLRs combined with high density of tumor infiltrating lymphocytes predicts a better prognosis in colorectal cancer patients[J]. PLoS One, 2023, 18(1): e0280085. doi: 10.1371/journal.pone.0280085
[17]	KARJULA T, ELOMAA H, NISKAKANGAS A, et al. CD3+ and CD8+ T-cell-based immune cell score and PD-(L)1 expression in pulmonary metastases of microsatellite stable colorectal cancer[J]. Cancers, 2022, 15(1): 206. doi: 10.3390/cancers15010206
[18]	SHEMBREY C, FOROUTAN M, HOLLANDE F. A new natural killer cell-specific gene signature predicting recurrence in colorectal cancer patients[J]. Front Immunol, 2022, 13: 1011247.
[19]	ZHAO X J, LIU J Z, LIU S Z, et al. Construction and validation of an immune-related prognostic model based on TP53 status in colorectal cancer[J]. Cancers, 2019, 11(11): 1722. doi: 10.3390/cancers11111722
[20]	GE J, LIU S L, ZHENG J X, et al. RNA demethylase ALKBH5 suppresses tumorigenesis via inhibiting proliferation and invasion and promoting CD8+ T cell infiltration in colorectal cancer[J]. Transl Oncol, 2023, 34: 101683. doi: 10.1016/j.tranon.2023.101683
[21]	CHEN H R, PAN Y S, ZHOU Q M, et al. METTL3 inhibits antitumor immunity by targeting m6A-BHLHE41-CXCL1/CXCR2 axis to promote colorectal cancer[J]. Gastroenterology, 2022, 163(4): 891-907. doi: 10.1053/j.gastro.2022.06.024
[22]	KATSUYA N, SENTANI K, SEKINO Y, et al. Clinicopathological significance of intelectin-1 in colorectal cancer: Intelectin-1 participates in tumor suppression and favorable progress[J]. Pathol Int, 2020, 70(12): 943-952. doi: 10.1111/pin.13027
[23]	CORRALES L, HIPP S, MARTIN K, et al. LY6G6D is a selectively expressed colorectal cancer antigen that can be used for targeting a therapeutic T-cell response by a T-cell engager[J]. Front Immunol, 2022, 13: 1008764. doi: 10.3389/fimmu.2022.1008764
[24]	SAJADI M, FAZILTI M, NAZEM H, et al. The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis[J]. Cancer Cell Int, 2022, 22(1): 339. doi: 10.1186/s12935-022-02751-3
[25]	DRURY J, RYCHAHOU P G, KELSON C O, et al. Upregulation of CD36, a fatty acid translocase, promotes colorectal cancer metastasis by increasing MMP28 and decreasing E-cadherin expression[J]. Cancers, 2022, 14(1): 252. doi: 10.3390/cancers14010252

[1]	SHEN Yi, JING Ying. Efficacy of Aiyu Capsule combined with FOLFOX4 chemotherapy in treatment of median or advanced rectum cancer and its impacts on cellular immunity and survival[J]. Journal of Clinical Medicine in Practice, 2024, 28(23): 58-64. DOI: 10.7619/jcmp.20242114
[2]	HUANG Xiaoli, HUANG Xiaoyan, SONG Shuhui, ZHANG Ying. Correlations of prognostic nutritional index and modified Glasgow prognostic score with prognosis in patients with cervical cancer[J]. Journal of Clinical Medicine in Practice, 2024, 28(20): 12-17. DOI: 10.7619/jcmp.20233927
[3]	GAO Qingling, CHANG Yan, WANG Jingni, ZHANG Jing, SUN Qingke. Effects of individual or combination medication of epidermal growth factor receptor tyrosine kinase inhibitor combined with chemotherapy on progression-free survival in advanced non-small cell lung cancer patients with epidermal growth factor receptor mutation[J]. Journal of Clinical Medicine in Practice, 2023, 27(24): 1-6. DOI: 10.7619/jcmp.20233042
[4]	WU Yang, YUAN Chengjia, YANG Die, ZHANG Xiaochun. Effect of Shenmai Injection on survival of patients with gastric cancer in phase Ⅱ to Ⅲ based on propensity score matching[J]. Journal of Clinical Medicine in Practice, 2023, 27(14): 46-50, 57. DOI: 10.7619/jcmp.20231064
[5]	LIU Shenxiang, XU Yongcheng, YAN Xuebing, MAO Haiyan, YE Qian. Influence of clinicopathological characteristics of elderly patients with left and right colon cancer on prognosis[J]. Journal of Clinical Medicine in Practice, 2023, 27(4): 113-116, 122. DOI: 10.7619/jcmp.20223286
[6]	WU Haoming, FU Guangbo. Clinical significance of long non-coding RNA SChLAP1 expression in prostate cancer tissue and its relationship with prognosis[J]. Journal of Clinical Medicine in Practice, 2022, 26(5): 30-33. DOI: 10.7619/jcmp.20214427
[7]	WU Xin, LIANG Bo. Construction of a postoperative survival nomogram for breast cancer based on ultrasound and cancer indicators[J]. Journal of Clinical Medicine in Practice, 2021, 25(23): 62-68. DOI: 10.7619/jcmp.20213928
[8]	XING Haiyang, ZHANG Yandi, WANG Kexin. Analysis on effect of radiotherapy on the survival of cervical cancer based on SEER database[J]. Journal of Clinical Medicine in Practice, 2020, 24(6): 15-19. DOI: 10.7619/jcmp.202006005
[9]	ZHANG Wei. Application of TIME-H principles in holistic nursing for patients with chronic venous ulcers in lower limbs[J]. Journal of Clinical Medicine in Practice, 2016, (14): 56-58. DOI: 10.7619/jcmp.201614018
[10]	XING Ze, WANG Hua, HU Qun, ZHAO Haiyan, SU Wuyun. Risk factors and survival analysis of locally advanced non-small cell lung cancer with brain metastasis[J]. Journal of Clinical Medicine in Practice, 2015, (23): 24-27. DOI: 10.7619/jcmp.201523008

Cited By

Cited by

Periodical cited type(3)

1.	费晓舟，金淦，马玉亮. 利伐沙班对腹腔镜疝修补术后出血和血栓形成的影响. 中国药物应用与监测. 2024(04): 438-441 .
2.	王琳，尚文强，李艳蔚. 肩关节镜不同入路方式在创伤性肩关节脱位中的应用效果及安全性. 临床误诊误治. 2023(01): 90-94 .
3.	邵超，高文灿，张军，沈滨，许建伟，殷凯. 普通外科术后下肢深静脉血栓形成预测模型的建立. 实用临床医药杂志. 2022(22): 12-15+19 . 本站查看

Other cited types(1)

Get Citation

PDF

XML

Article views (231) PDF downloads (37) Cited by(4)

Turn off MathJax

Article Contents

Abstract

References

Construction and validation of a risk model for colorectal cancer prognosis based on N6-methyladenosine modification and immune infiltration