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An individualized prognostic signature for gastric cancer patients treated with 5-Fluorouracil-based chemotherapy and distinct multi-omics characteristics of prognostic groups.

ABSTRACT: 5-Fluorouracil (5-FU)-based chemotherapy is currently the first-line treatment for gastric cancer. In this study, using gene expression profiles for a panel of cell lines with drug sensitivity data and two cohorts of patients, we extracted a signature consisting of two gene pairs (KCNE2 and API5, KCNE2 and PRPF3) whose within-sample relative expression orderings (REOs) could robustly predict prognoses of gastric cancer patients treated with 5-FU-based chemotherapy. This REOs-based signature was insensitive to experimental batch effects and could be directly applied to samples measured by different laboratories. Taking this unique advantage of the REOs-based signature, we classified gastric cancer samples of The Cancer Genome Atlas (TCGA) into two prognostic groups with distinct transcriptional characteristics, circumventing the usage of confounded TCGA survival data. We further showed that the two prognostic groups displayed distinct copy number, gene mutation and DNA methylation landscapes using the TCGA multi-omics data. The results provided hints for understanding molecular mechanisms determining prognoses of gastric cancer patients treated with 5-FU-based chemotherapy.

SUBMITTER: Li X

PROVIDER: S-EPMC4891001 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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An individualized prognostic signature for gastric cancer patients treated with 5-Fluorouracil-based chemotherapy and distinct multi-omics characteristics of prognostic groups.

Li Xiangyu X Cai Hao H Zheng Weicheng W Tong Mengsha M Li Hongdong H Ao Lu L Li Jing J Hong Guini G Li Mengyao M Guan Qingzhou Q Yang Sheng S Yang Da D Lin Xu X Guo Zheng Z

Oncotarget 20160201 8

5-Fluorouracil (5-FU)-based chemotherapy is currently the first-line treatment for gastric cancer. In this study, using gene expression profiles for a panel of cell lines with drug sensitivity data and two cohorts of patients, we extracted a signature consisting of two gene pairs (KCNE2 and API5, KCNE2 and PRPF3) whose within-sample relative expression orderings (REOs) could robustly predict prognoses of gastric cancer patients treated with 5-FU-based chemotherapy. This REOs-based signature was ...[more]

PMID: 26840027

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Project description:BackgroundHigh expression of Stathmin 1 (STMN1) protein is related to a poor prognosis in various tumors, including breast cancer. In our previous study, a phospho-STMN1 signature was conducted to predict outcomes in adjuvantly treated breast cancer patients. This study aimed to explore the relationship of STMN1 expression with our phospho-STMN1 signature and the prognosis of patients treated with neoadjuvant chemotherapy (NACT).MethodsA retrospective analysis of 116 patients who received NACT in The First Affiliated Hospital of Sun Yat-sen University between December 2008 and March 2016 was conducted. Patients were followed up through telephone once a year until 2022. The levels of STMN1, Ser16, Ser25, Ser38, and Ser63 phosphorylation and GRP78 expression in pre-NACT biopsy specimens from the patients were detected by immunohistochemistry. The recurrence risk score for each patient was calculated using the p-STMN1/GRP78 model. Clinical and pathological parameters, pathological complete response and objective response rates, and survival data were analyzed.ResultsIn patients with NACT-treated breast cancer, high levels of STMN1, Ser25 phosphorylation, Ser38 phosphorylation, and GRP78 were related to worse disease-free survival (DFS), as was a high p-STMN1/GRP78 model risk score. In contrast, high Ser16 and Ser63 phosphorylation levels were related to better DFS [p-STMN1/GRP78 model: P=0.002, HR =0.180 (0.061-0.534); STMN1: P=0.001, HR =0.290 (0.147-0.572); Ser16: P=0.036, HR =2.019 (1.049-3.886); Ser25: P=0.013, HR =0.392 (0.188-0.819); Ser38: P=0.001, HR =0.293 (0.153-0.559); Ser63: P=0.006, HR =3.346 (1.407-7.961); GRP78: P=0.010, HR =0.417 (0.214-0.815)]. However, no significant statistical difference was found in the multivariate regression. The relationship between these markers and the therapeutic effect of NACT (pathological complete response and objective response) showed the same tendency with survival. The area under the receiver operating characteristic curve for the p-STMN1/GRP78 model was 0.790 (P=0.001) with sensitivity of 70% and specificity of 74%.ConclusionsThe expression and serine phosphorylation status of STMN1 may be beneficial as biomarkers for predicting the prognosis of breast cancer patients treated with NACT. Our p-STMN1/GRP78 model could become a widely applied signature for assessing the metastatic risk of breast cancer patients, potentially facilitating their individualized management before NACT.

Dataset Information

An individualized prognostic signature for gastric cancer patients treated with 5-Fluorouracil-based chemotherapy and distinct multi-omics characteristics of prognostic groups.

Publications

An individualized prognostic signature for gastric cancer patients treated with 5-Fluorouracil-based chemotherapy and distinct multi-omics characteristics of prognostic groups.

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