Dataset Information

The Key Genes for Perineural Invasion in Pancreatic Ductal Adenocarcinoma Identified With Monte-Carlo Feature Selection Method.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive form of pancreatic cancer. Its 5-year survival rate is only 3-5%. Perineural invasion (PNI) is a process of cancer cells invading the surrounding nerves and perineural spaces. It is considered to be associated with the poor prognosis of PDAC. About 90% of pancreatic cancer patients have PNI. The high incidence of PNI in pancreatic cancer limits radical resection and promotes local recurrence, which negatively affects life quality and survival time of the patients with pancreatic cancer.

Objectives

To investigate the mechanism of PNI in pancreatic cancer, we analyzed the gene expression profiles of tumors and adjacent tissues from 50 PDAC patients which included 28 patients with perineural invasion and 22 patients without perineural invasion.

Method

Using Monte-Carlo feature selection and Incremental Feature Selection (IFS) method, we identified 26 key features within which 15 features were from tumor tissues and 11 features were from adjacent tissues.

Results

Our results suggested that not only the tumor tissue, but also the adjacent tissue, was informative for perineural invasion prediction. The SVM classifier based on these 26 key features can predict perineural invasion accurately, with a high accuracy of 0.94 evaluated with leave-one-out cross validation (LOOCV).

Conclusion

The in-depth biological analysis of key feature genes, such as TNFRSF14, XPO1, and ATF3, shed light on the understanding of perineural invasion in pancreatic ductal adenocarcinoma.

SUBMITTER: Zhu JH

PROVIDER: S-EPMC7593847 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

The Key Genes for Perineural Invasion in Pancreatic Ductal Adenocarcinoma Identified With Monte-Carlo Feature Selection Method.

Zhu Jin-Hui JH Yan Qiu-Liang QL Wang Jian-Wei JW Chen Yan Y Ye Qing-Huang QH Wang Zhi-Jiang ZJ Huang Tao T

Frontiers in genetics 20201015

<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive form of pancreatic cancer. Its 5-year survival rate is only 3-5%. Perineural invasion (PNI) is a process of cancer cells invading the surrounding nerves and perineural spaces. It is considered to be associated with the poor prognosis of PDAC. About 90% of pancreatic cancer patients have PNI. The high incidence of PNI in pancreatic cancer limits radical resection and promotes local recurrence, which negatively affec ...[more]

PMID: 33193628

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Project description:PurposeCurative intent treatment of pancreatic adenocarcinoma (PDAC) relies on surgical resection. Modern treatment protocols focus on optimizing neoadjuvant therapy to increase resectability and improve oncologic outcomes. To elucidate differences in outcomes, we investigated the relationship between neoadjuvant chemotherapy (NAC), either with or without stereotactic body radiation therapy (SBRT), and vascular inflammation, surgical outcomes, and the resultant transcriptomic changes.Methods and materialsClinical data were collected from patients with borderline resectable PDAC (clinical T3-T4N0-1) who underwent NAC or NAC-SBRT followed by curative intent resection between 2014 and 2019. Vascular structures on surgical specimens were histologically evaluated for vasculitis. RNA sequencing was used to evaluate differential gene expression and to generate enrichment maps. Multivariate analysis was used to analyze the relationship between patient characteristics and oncological outcome.ResultsIn total, 46 patients met inclusion criteria (n = 12 NAC, n = 34 NAC-SBRT) with a median follow-up of 20.1 months. All patients underwent curative resection, with 91.3% achieving R0. There was no significant difference in patterns of failure, overall survival, or progression-free survival between NAC and NAC-SBRT groups. Patients with vasculitis had a lower median overall survival compared with those without (14.5 vs 28.3 months; hazard ratio, 12.96; 95% confidence interval, 3.55-47.28; P < .001). There was no significant correlation between inflammation and surgical complications or pathologic response. Neoadjuvant therapy did not have a significant effect on development of vasculitis (odds radio, 1.64 for NAC-SBRT; 95% confidence interval, 0.40-8.43; P = .52). Predictors of poor survival included perineural invasion and high baseline carbohydrate antigen 19-9 (CA19-9) (>191 U/mL). Patients with robust CA19-9 (>20% decrease) responses to neoadjuvant therapy had enrichment in immune response, chemotaxis, and cytotoxic T-cell and natural killer-cell proliferation.ConclusionsVasculitis predicts for poor survival outcomes in patients with PDAC; NAC-SBRT did not increase the rate of vasculitis compared with NAC. Perineural invasion and CA19-9 remain strong prognosticators. Understanding and optimizing immune interactions remain a crucial hurdle in achieving response in pancreatic cancer.

Dataset Information

The Key Genes for Perineural Invasion in Pancreatic Ductal Adenocarcinoma Identified With Monte-Carlo Feature Selection Method.

Background

Objectives

Method

Results

Conclusion

Publications

The Key Genes for Perineural Invasion in Pancreatic Ductal Adenocarcinoma Identified With Monte-Carlo Feature Selection Method.

Similar Datasets

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