Cuproptosis-Associated lncRNA Gene Signature Establishes New Prognostic Profile and Predicts Immunotherapy Response in Endometrial Carcinoma

被引:0
|
作者
Jiang, Xi-Ya [1 ,2 ]
Hu, Jing-Jing [1 ,3 ]
Wang, Rui [4 ]
Zhang, Wei-Yu [1 ,2 ]
Jin, Qin-Qin [1 ,2 ]
Yang, Yin-Ting [1 ,2 ]
Mei, Jie [1 ,2 ]
Hong, Lin [1 ,2 ]
Yao, Hui [1 ,2 ]
Tao, Feng [1 ,2 ]
Li, Jie-Jie [1 ,2 ]
Liu, Yu [1 ,2 ]
Zhang, Li [1 ,2 ]
Chen, Shun-Xia [1 ,2 ]
Chen, Guo [1 ,2 ]
Song, Yang [5 ]
Zhou, Shu-Guang [1 ,2 ]
机构
[1] Anhui Med Univ, Anhui Prov Matern & Child Healthcare Hosp, Dept Gynecol & Obstet, Matern & Child Healthcare Hosp, Hefei 230001, Anhui, Peoples R China
[2] Anhui Med Univ, Clin Coll 5, Dept Gynecol & Obstet, Hefei 230032, Anhui, Peoples R China
[3] Anhui Med Univ, Affiliated Hosp 1, Dept Reprod, Hefei 230032, Anhui, Peoples R China
[4] Anhui Prov Matern & Child Healthcare Hosp, Dept Clin Lab, Hefei 230001, Anhui, Peoples R China
[5] Anhui Med Univ, Affiliated Hosp 1, Dept Pain, Hefei 230032, Anhui, Peoples R China
关键词
Cuproptosis; Long non-coding RNA; Endometrial cancer; Prognostic signature; Immune landscape; CANCER; COPPER; IDENTIFICATION; VALIDATION; STRESS; PATHS;
D O I
10.1007/s10528-023-10574-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment.Methods: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed. Results: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated. Conclusions: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic.
引用
收藏
页码:3439 / 3466
页数:28
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