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The CINSARC signature as a prognostic marker for clinical outcome in multiple neoplasms.

ABSTRACT: We previously reported the CINSARC signature as a prognostic marker for metastatic events in soft tissue sarcomas, breast carcinomas and lymphomas through genomic instability, acting as a major factor for tumor aggressiveness. In this study, we used a published resource to investigate CINSARC enrichment in poor outcome-associated genes at pan-cancer level and in 39 cancer types. CINSARC outperformed more than 15,000 defined signatures (including cancer-related), being enriched in top-ranked poor outcome-associated genes of 21 cancer types, widest coverage reached among all tested signatures. Independently, this signature demonstrated significant survival differences between risk-groups in 33 published studies, representing 17 tumor types. As a consequence, we propose the CINSARC prognostication as a general marker for tumor aggressiveness to optimize the clinical managements of patients.

SUBMITTER: Lesluyes T

PROVIDER: S-EPMC5511191 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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The CINSARC signature as a prognostic marker for clinical outcome in multiple neoplasms.

Lesluyes Tom T Delespaul Lucile L Coindre Jean-Michel JM Chibon Frédéric F

Scientific reports 20170714 1

We previously reported the CINSARC signature as a prognostic marker for metastatic events in soft tissue sarcomas, breast carcinomas and lymphomas through genomic instability, acting as a major factor for tumor aggressiveness. In this study, we used a published resource to investigate CINSARC enrichment in poor outcome-associated genes at pan-cancer level and in 39 cancer types. CINSARC outperformed more than 15,000 defined signatures (including cancer-related), being enriched in top-ranked poor ...[more]

PMID: 28710396

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Project description:BackgroundOne of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively.Methods and findingsOur results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER- patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome.ConclusionsThe 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic value for both ER-positive and ER-negative breast cancer. The signature was selected using a novel biological approach and hence holds promise to represent the key biological processes of breast cancer.

Project description:BackgroundAs public awareness of health has increased and diagnostic and treatment options have improved, the survival of patients with malignant tumors has continued to extend, and the population has been aging, the number of multiple primary malignant neoplasms has gradually increased in recent years. There are few reports concerning female patients with multiple primary malignant neoplasms of breast cancer or genitalia malignancies. In this study, we aimed to analyze the clinical characteristics and prognosis of multiple primary malignant neoplasms in female patients with breast cancer or genitalia malignancies, as well as further explore the factors that affect the survival.MethodsWe collected clinical data on 80 female patients diagnosed with multiple primary malignant neoplasms of the breast or genitalia, described their clinical features. Furthermore, we calculated the survival and prognostic factors for 52 participants.ResultsIn our study, the prevalence rate of multiple primary malignant neoplasms was 0.66% (367/55404). Corresponding to female patients with multiple primary malignant neoplasms of breast cancer or genitalia malignancies, it was 1.4% (80/5707). the median age of diagnosis for the first tumor was 48 years, and the median age of diagnosis for the second tumor was 52 years. Regarding the interval, 67.57% (50/74) of patients were within five years. Most tumors were located in the breast (44.68%), followed by the uterus (20.21%), the ovary (17.02%), and the cervix (15.96%). The overall 12-, 36-and 60-month survival rates of the patients were 86.4%, 74.3%, and 69.8%. For the female patients, the stage (III-IV) (P = 0.046), non-radical surgery (P = 0.002), and types of the last tumor (breast cancer or genitalia malignancies) (P = 0.019) were associated with the poor prognosis.ConclusionsFemale patients with breast cancer or genital malignancies should pay attention to screening for the second tumor, especially within 4 years after the first tumor diagnosed. Furthermore, during tumor screening, it may be recommended for these patients to focus on colorectal cancer and lung cancer. Compared with previous studies, in addition to clinical staging and types of surgery, we found whether the last tumor was breast cancer or genitalia malignancies should also be considered a prognostic factor.

Dataset Information

The CINSARC signature as a prognostic marker for clinical outcome in multiple neoplasms.

Publications

The CINSARC signature as a prognostic marker for clinical outcome in multiple neoplasms.

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