Construction and validation of a gastric cancer prognostic model based on disulfidptosis-related genes_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Shuo ^1,2,3 , ZHU Lihui ^2,3,4 , LIAO Tianyi ^1,2,3 , ZHANG Xiang ^1,2,3 ,  CAI Hui ^1,2,3,4

1. First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China;
2. Clinical Center of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, P. R. China;
3. Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Lanzhou 730000, P. R. China;
4. School of Clinical Medicine, Ningxia Medical University, Yinchuan 750000, P. R. China;

Corresponding author：

CAI Hui, Email: caialonteam@163.com

Keywords：

gastric cancer; disulfidptosis; prognostic model; risk score

DOI：

10.7507/1007-9424.202307041

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To onstructe a prognostic model for gastric cancer based on disulfidoptosis-related genes. Methods Firstly, transcriptome data and clinical data were obtained from the TCGA and GEO databases to explore the expression of disulfidoptosis-related genes in gastric cancer tissues and normal tissues, as well as their impact on the overall survival (OS) of gastric cancer patients. Subsequently, two clusters of disulfidoptosis-related gene were determined by consensus clustering, key genes were further selected by using LASSO regression, and a multivariate Cox proportional hazards regression model was constructed to predict OS. Results Among the 24 kinds of disulfidoptosis-associated genes, 16 exhibited statistically significant differences in expression between gastric cancer tissues and normal tissues (P<0.05), and results of univariate Cox proportional hazards regression model showed that 9 kinds of disulfidoptosis-associated genes were associated with OS (P<0.05). The 24 kinds of disulfidoptosis-associated genes were grouped into 2 clusters by using the consensus clustering algorithm, with 299 differentially expressed genes between the two clusters. In the training set, 14 genes were determined by using LASSO regression to construct the OS prediction model, and risk scores were calculated. The OS of the high-risk group was significantly worse than that of the low-risk group (P<0.05), and this prediction model also had a high area under the curve value in the validation set. Conclusions The OS prediction model based on disulfidoptosis-associated genes can predict the prognosis of gastric cancer patients.

Citation： LIU Shuo, ZHU Lihui, LIAO Tianyi, ZHANG Xiang, CAI Hui. Construction and validation of a gastric cancer prognostic model based on disulfidptosis-related genes. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(11): 1333-1340. doi: 10.7507/1007-9424.202307041 Copy

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7.	Zhao S, Wang L, Ding W, et al. Crosstalk of disulfidptosis-related subtypes, establishment of a prognostic signature and immune infiltration characteristics in bladder cancer based on a machine learning survival framework. Front Endocrinol (Lausanne), 2023, 14: 1180404. doi: 10.3389/fendo.2023.1180404.
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10.	Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res, 2015, 43(7): e47. doi: 10.1093/nar/gkv007.
11.	Yu G, Wang LG, Han Y, et al. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS, 2012, 16(5): 284-287.
12.	Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer. CA Cancer J Clin, 2021, 71(3): 264-279.
13.	Wang Y, Zhang L, Yang Y, et al. Progress of gastric cancer surgery in the era of precision medicine. Int J Biol Sci, 2021, 17(4): 1041-1049.
14.	Xie J, Fu L, Jin L. Immunotherapy of gastric cancer: past, future perspective and challenges. Pathol Res Pract, 2021, 218: 153322. doi: 10.1016/j.prp.2020.153322.
15.	姜志超, 周爱萍. 晚期胃癌一线免疫治疗的现状与进展. 中国肿瘤临床, 2023, 50(4): 206-211.
16.	蒋金玲, 周尘飞, 王超, 等. 2022年度胃癌研究和诊疗新进展. 中国癌症杂志, 2023, 33(4): 303-314.
17.	Meng Y, Chen X, Deng G. Disulfidptosis: a new form of regulated cell death for cancer treatment. Mol Biomed, 2023, 4(1): 18. doi: 10.1186/s43556-023-00132-4.
18.	Kim S, Jana B, Go EM, et al. Intramitochondrial disulfide polymerization controls cancer cell fate. ACS Nano, 2021, 15(9): 14492-14508.
19.	Yang S, Li D, Chen L, et al. Coupling metal organic frameworks with molybdenum disulfide nanoflakes for targeted cancer theranostics. Biomater Sci, 2021, 9(9): 3306-3318.
20.	Zhang AZ, Yuan X, Liang WH, et al. Immune infiltration in gastric cancer microenvironment and its clinical significance. Front Cell Dev Biol, 2022, 9: 762029. doi: 10.3389/fcell.2021.762029.
21.	Liu X, Olszewski K, Zhang Y, et al. Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. Nat Cell Biol, 2020, 22(4): 476-486.
22.	Feng Z, Zhao Q, Ding Y, et al. Identification a unique disulfidptosis classification regarding prognosis and immune landscapes in thyroid carcinoma and providing therapeutic strategies. J Cancer Res Clin Oncol, 2023, 149(13): 11157-11170.
23.	Chen Y, Jin C, Cui J, et al. Single-cell sequencing and bulk RNA data reveal the tumor microenvironment infiltration characteristics of disulfidptosis related genes in breast cancer. J Cancer Res Clin Oncol, 2023, 149(13): 12145-12164.
24.	Wang T, Guo K, Zhang D, et al. Disulfidptosis classification of hepatocellular carcinoma reveals correlation with clinical prognosis and immune profile. Int Immunopharmacol, 2023, 120: 110368. doi: 10.1016/j.intimp.2023.110368.
25.	Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol, 2013, 13(4): 227-242.
26.	史建伟, 李永吉, 高铁铭, 等. 胃癌组织中FLNa、VEGF和MVD的相关性. 医学研究与教育, 2019, 36(2): 17-22.
27.	Feng Z, Hom ME, Bearrood TE, et al. Targeting colorectal cancer with small-molecule inhibitors of ALDH1B1. Nat Chem Biol, 2022, 18(10): 1065-1075.
28.	Chen X, Huang J, Yu C, et al. A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis. Nat Commun, 2022, 13(1): 6318. doi: 10.1038/s41467-022-34096-w.
29.	Taniguchi S, Elhance A, Van Duzer A, et al. Tumor-initiating cells establish an IL-33-TGF-β niche signaling loop to promote cancer progression. Science, 2020, 369(6501): eaay1813. doi: 10.1126/science.aay1813.
30.	Zheng L, Li S, Zheng X, et al. AHNAK2 is a novel prognostic marker and correlates with immune infiltration in papillary thyroid cancer: Evidence from integrated analysis. Int Immunopharmacol, 2021, 90: 107185. doi: 10.1016/j.intimp.2020.107185.
31.	Zhang N, Li L, Luo J, et al. Inhibiting microRNA-424 in bone marrow mesenchymal stem cells-derived exosomes suppresses tumor growth in colorectal cancer by upregulating TGFBR3. Arch Biochem Biophys, 2021, 709: 108965. doi: 10.1016/ j.abb.2021.108965.
32.	Hou X, Yang L, Wang K, et al. HELLS, a chromatin remodeler is highly expressed in pancreatic cancer and downregulation of it impairs tumor growth and sensitizes to cisplatin by reexpressing the tumor suppressor TGFBR3. Cancer Med, 2021, 10(1): 350-364.
33.	Zhang X, Huang T, Li Y, et al. Upregulation of THBS1 is related to immunity and chemotherapy resistance in gastric cancer. Int J Gen Med, 2021, 14: 4945-4957.
34.	Yang L, Yang Z, Zuo C, et al. Epidemiological evidence for associations between variants in CHRNA genes and risk of lung cancer and chronic obstructive pulmonary disease. Front Oncol, 2022, 12: 1001864. doi: 10.3389/fonc.2022.1001864.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Zeng Y, Jin RU. Molecular pathogenesis, targeted therapies, and future perspectives for gastric cancer. Semin Cancer Biol, 2022, 86(Pt 3): 566-582.
3. Boehm JS, Garnett MJ, Adams DJ, et al. Cancer research needs a better map. Nature, 2021, 589(7843): 514-516.
4. Liu X, Nie L, Zhang Y, et al. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. Nat Cell Biol, 2023, 25(3): 404-414.
5. Hogg PJ. Biological regulation through protein disulfide bond cleavage. Redox Rep, 2002, 7(2): 71-77.
6. Daly EB, Wind T, Jiang XM, et al. Secretion of phosphoglycerate kinase from tumour cells is controlled by oxygen-sensing hydroxylases. Biochim Biophys Acta, 2004, 1691(1): 17-22.
7. Zhao S, Wang L, Ding W, et al. Crosstalk of disulfidptosis-related subtypes, establishment of a prognostic signature and immune infiltration characteristics in bladder cancer based on a machine learning survival framework. Front Endocrinol (Lausanne), 2023, 14: 1180404. doi: 10.3389/fendo.2023.1180404.
8. Wilkerson MD, Hayes DN. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics, 2010, 26(12): 1572-1573.
9. Zhao S, Zhang X, Gao F, et al. Identification of copper metabolism-related subtypes and establishment of the prognostic model in ovarian cancer. Front Endocrinol (Lausanne), 2023, 14: 1145797. doi: 10.3389/fendo.2023.1145797.
10. Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res, 2015, 43(7): e47. doi: 10.1093/nar/gkv007.
11. Yu G, Wang LG, Han Y, et al. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS, 2012, 16(5): 284-287.
12. Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer. CA Cancer J Clin, 2021, 71(3): 264-279.
13. Wang Y, Zhang L, Yang Y, et al. Progress of gastric cancer surgery in the era of precision medicine. Int J Biol Sci, 2021, 17(4): 1041-1049.
14. Xie J, Fu L, Jin L. Immunotherapy of gastric cancer: past, future perspective and challenges. Pathol Res Pract, 2021, 218: 153322. doi: 10.1016/j.prp.2020.153322.
15. 姜志超, 周爱萍. 晚期胃癌一线免疫治疗的现状与进展. 中国肿瘤临床, 2023, 50(4): 206-211.
16. 蒋金玲, 周尘飞, 王超, 等. 2022年度胃癌研究和诊疗新进展. 中国癌症杂志, 2023, 33(4): 303-314.
17. Meng Y, Chen X, Deng G. Disulfidptosis: a new form of regulated cell death for cancer treatment. Mol Biomed, 2023, 4(1): 18. doi: 10.1186/s43556-023-00132-4.
18. Kim S, Jana B, Go EM, et al. Intramitochondrial disulfide polymerization controls cancer cell fate. ACS Nano, 2021, 15(9): 14492-14508.
19. Yang S, Li D, Chen L, et al. Coupling metal organic frameworks with molybdenum disulfide nanoflakes for targeted cancer theranostics. Biomater Sci, 2021, 9(9): 3306-3318.
20. Zhang AZ, Yuan X, Liang WH, et al. Immune infiltration in gastric cancer microenvironment and its clinical significance. Front Cell Dev Biol, 2022, 9: 762029. doi: 10.3389/fcell.2021.762029.
21. Liu X, Olszewski K, Zhang Y, et al. Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. Nat Cell Biol, 2020, 22(4): 476-486.
22. Feng Z, Zhao Q, Ding Y, et al. Identification a unique disulfidptosis classification regarding prognosis and immune landscapes in thyroid carcinoma and providing therapeutic strategies. J Cancer Res Clin Oncol, 2023, 149(13): 11157-11170.
23. Chen Y, Jin C, Cui J, et al. Single-cell sequencing and bulk RNA data reveal the tumor microenvironment infiltration characteristics of disulfidptosis related genes in breast cancer. J Cancer Res Clin Oncol, 2023, 149(13): 12145-12164.
24. Wang T, Guo K, Zhang D, et al. Disulfidptosis classification of hepatocellular carcinoma reveals correlation with clinical prognosis and immune profile. Int Immunopharmacol, 2023, 120: 110368. doi: 10.1016/j.intimp.2023.110368.
25. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol, 2013, 13(4): 227-242.
26. 史建伟, 李永吉, 高铁铭, 等. 胃癌组织中FLNa、VEGF和MVD的相关性. 医学研究与教育, 2019, 36(2): 17-22.
27. Feng Z, Hom ME, Bearrood TE, et al. Targeting colorectal cancer with small-molecule inhibitors of ALDH1B1. Nat Chem Biol, 2022, 18(10): 1065-1075.
28. Chen X, Huang J, Yu C, et al. A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis. Nat Commun, 2022, 13(1): 6318. doi: 10.1038/s41467-022-34096-w.
29. Taniguchi S, Elhance A, Van Duzer A, et al. Tumor-initiating cells establish an IL-33-TGF-β niche signaling loop to promote cancer progression. Science, 2020, 369(6501): eaay1813. doi: 10.1126/science.aay1813.
30. Zheng L, Li S, Zheng X, et al. AHNAK2 is a novel prognostic marker and correlates with immune infiltration in papillary thyroid cancer: Evidence from integrated analysis. Int Immunopharmacol, 2021, 90: 107185. doi: 10.1016/j.intimp.2020.107185.
31. Zhang N, Li L, Luo J, et al. Inhibiting microRNA-424 in bone marrow mesenchymal stem cells-derived exosomes suppresses tumor growth in colorectal cancer by upregulating TGFBR3. Arch Biochem Biophys, 2021, 709: 108965. doi: 10.1016/ j.abb.2021.108965.
32. Hou X, Yang L, Wang K, et al. HELLS, a chromatin remodeler is highly expressed in pancreatic cancer and downregulation of it impairs tumor growth and sensitizes to cisplatin by reexpressing the tumor suppressor TGFBR3. Cancer Med, 2021, 10(1): 350-364.
33. Zhang X, Huang T, Li Y, et al. Upregulation of THBS1 is related to immunity and chemotherapy resistance in gastric cancer. Int J Gen Med, 2021, 14: 4945-4957.
34. Yang L, Yang Z, Zuo C, et al. Epidemiological evidence for associations between variants in CHRNA genes and risk of lung cancer and chronic obstructive pulmonary disease. Front Oncol, 2022, 12: 1001864. doi: 10.3389/fonc.2022.1001864.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Construction and validation of a gastric cancer prognostic model based on disulfidptosis-related genes

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