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胰头癌与胰体/尾癌之间可区分的预后特征及肿瘤免疫原性

Distinguishable Prognostic Signatures and Tumor Immunogenicity Between Pancreatic Head Cancer and Pancreatic Body/Tail Cancer.

作者信息

Ge Weiyu, Ma Jingyu, Mao Tiebo, Xu Haiyan, Zhang Xiaofei, Li Shumin, Wang Yongchao, Yao Jiayu, Yue Ming, Jiao Feng, Wang Yu, Zhuo Meng, Han Ting, Hu Jiong, Zhang Xiao, Cui Jiujie, Wang Liwei

机构信息

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Front Oncol. 2022 Jun 8;12:890715. doi: 10.3389/fonc.2022.890715. eCollection 2022.

Abstract

BACKGROUND

Pancreatic head cancer and pancreatic body/tail cancer are considered to have different clinical presentations and to have altered outcomes.

METHODS

Ninety cases of pancreatic adenocarcinoma (PDAC) from our institution were used as a discovery set and 166 cases of PDAC from the TCGA cohort were used as a validation set. According to the anatomical location, the cases of PDAC were divided into the pancreatic head cancer group and the pancreatic body/tail cancer group. Firstly, the different biological functions of the two groups were assessed by ssGSEA. Meanwhile, ESTIMATE and CIBERSORT were conducted to estimate immune infiltration. Then, a novel anatomical site-related risk score (SRS) model was constructed by LASSO and Cox regression. Survival and time-dependent ROC analysis was used to prove the predictive ability of our model in two cohorts. Subsequently, an integrated survival decision tree and a scoring nomogram were constructed to improve prognostic stratification and predictive accuracy for individual patients. In addition, gseaGO and gseaKEGG pathway analyses were performed on genes in the key module by the R package.

RESULTS

Overall survival and the objective response rate (ORR) of patients with pancreatic body/tail cancer were markedly superior to those with pancreatic head cancer. In addition, distinct immune characteristics and gene patterns were observed between the two groups. Then, we screened 5 biomarkers related to the prognosis of pancreatic cancer and constructed a more powerful novel SRS model to predict prognosis.

CONCLUSIONS

Our research shed some light on the revelation of gene patterns, immune and mutational landscape characterizations, and their relationships in different PDAC locations.

摘要

背景

胰头癌和胰体/尾癌被认为具有不同的临床表现且预后有所改变。

方法

将来自我们机构的90例胰腺腺癌(PDAC)病例用作发现集,并将来自TCGA队列的166例PDAC病例用作验证集。根据解剖位置,将PDAC病例分为胰头癌组和胰体/尾癌组。首先,通过单样本基因集富集分析(ssGSEA)评估两组的不同生物学功能。同时,进行ESTIMATE和CIBERSORT分析以估计免疫浸润。然后,通过套索(LASSO)和Cox回归构建了一种新的与解剖部位相关的风险评分(SRS)模型。生存分析和时间依赖的受试者工作特征(ROC)分析用于证明我们模型在两个队列中的预测能力。随后,构建了综合生存决策树和评分列线图,以改善个体患者的预后分层和预测准确性。此外,通过R包对关键模块中的基因进行基因本体论(gseaGO)和京都基因与基因组百科全书(gseaKEGG)通路分析。

结果

胰体/尾癌患者的总生存期和客观缓解率(ORR)明显优于胰头癌患者。此外,两组之间观察到明显不同的免疫特征和基因模式。然后,我们筛选了5个与胰腺癌预后相关的生物标志物,并构建了一个更强大的新型SRS模型来预测预后。

结论

我们的研究为揭示不同PDAC部位的基因模式、免疫和突变图谱特征及其关系提供了一些线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c495/9213676/c4845d8d8491/fonc-12-890715-g001.jpg

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