A transfer learning approach via procrustes analysis and mean shift for cancer drug sensitivity prediction

2018 ◽  
Vol 16 (03) ◽  
pp. 1840014 ◽  
Author(s):  
Turki Turki ◽  
Zhi Wei ◽  
Jason T. L. Wang

Transfer learning (TL) algorithms aim to improve the prediction performance in a target task (e.g. the prediction of cisplatin sensitivity in triple-negative breast cancer patients) via transferring knowledge from auxiliary data of a related task (e.g. the prediction of docetaxel sensitivity in breast cancer patients), where the distribution and even the feature space of the data pertaining to the tasks can be different. In real-world applications, we sometimes have a limited training set in a target task while we have auxiliary data from a related task. To obtain a better prediction performance in the target task, supervised learning requires a sufficiently large training set in the target task to perform well in predicting future test examples of the target task. In this paper, we propose a TL approach for cancer drug sensitivity prediction, where our approach combines three techniques. First, we shift the representation of a subset of examples from auxiliary data of a related task to a representation closer to a target training set of a target task. Second, we align the shifted representation of the selected examples of the auxiliary data to the target training set to obtain examples with representation aligned to the target training set. Third, we train machine learning algorithms using both the target training set and the aligned examples. We evaluate the performance of our approach against baseline approaches using the Area Under the receiver operating characteristic (ROC) Curve (AUC) on real clinical trial datasets pertaining to multiple myeloma, nonsmall cell lung cancer, triple-negative breast cancer, and breast cancer. Experimental results show that our approach is better than the baseline approaches in terms of performance and statistical significance.

Cell Systems ◽  
2021 ◽  
Author(s):  
Marco Tognetti ◽  
Attila Gabor ◽  
Mi Yang ◽  
Valentina Cappelletti ◽  
Jonas Windhager ◽  
...  

Breast Care ◽  
2020 ◽  
pp. 1-9
Author(s):  
Rudolf Napieralski ◽  
Gabriele Schricker ◽  
Gert Auer ◽  
Michaela Aubele ◽  
Jonathan Perkins ◽  
...  

<b><i>Background:</i></b> PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. <b><i>Material and Methods:</i></b> The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. <b><i>Results:</i></b> The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1246
Author(s):  
Marta Sanz-Álvarez ◽  
Ion Cristóbal ◽  
Melani Luque ◽  
Andrea Santos ◽  
Sandra Zazo ◽  
...  

The bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal domain (BET) protein family, has emerged in the last years as a promising molecular target in many tumors including breast cancer. The triple negative breast cancer (TNBC) represents the molecular subtype with the worst prognosis and a current therapeutic challenge, and TNBC cells have been reported to show a preferential sensitivity to BET inhibitors. Interestingly, BRD4 phosphorylation (pBRD4) was found as an alteration that confers resistance to BET inhibition and PP2A proposed as the phosphatase responsible to regulate pBRD4 levels. However, the potential clinical significance of pBRD4, as well as its potential correlation with the PP2A pathway in TNBC, remains to be investigated. Here, we evaluated the expression levels of pBRD4 in a series of 132 TNBC patients. We found high pBRD4 levels in 34.1% of cases (45/132), and this alteration was found to be associated with the development of patient recurrences (p = 0.007). Interestingly, BRD4 hyperphosphorylation predicted significantly shorter overall (p < 0.001) and event-free survival (p < 0.001). Moreover, multivariate analyses were performed to confirm its independent prognostic impact in our cohort. In conclusion, our findings show that BRD4 hyperphosphorylation is an alteration associated with PP2A inhibition that defines a subgroup of TNBC patients with unfavorable prognosis, suggesting the potential clinical and therapeutic usefulness of the PP2A/BRD4 axis as a novel molecular target to overcome resistance to treatments based on BRD4 inhibition.


2021 ◽  
Vol 32 ◽  
pp. S43-S44
Author(s):  
K.S. Harborg ◽  
R. Zachariae ◽  
J. Olsen ◽  
M. Johannsen ◽  
D. Cronin-Fenton ◽  
...  

2021 ◽  
Vol 13 ◽  
pp. 175883592110066
Author(s):  
Eriko Katsuta ◽  
Li Yan ◽  
Mateusz Opyrchal ◽  
Pawel Kalinski ◽  
Kazuaki Takabe

Background: Cytotoxic T-lymphocyte (CTL) infiltration into tumor is a positive prognostic factor in breast cancer. High tumor mutational burden (TMB) is also considered as a predictor of tumor immunogenicity and response to immunotherapy. However, it is unclear whether the infiltration of functional CTL simply reflects the TMB or represents an independent prognostic value. Methods: Utilizing The Cancer Genome Atlas (TCGA) breast cancer cohort, we established the Functional Hotness Score (FHS). The associations of FHS and breast cancer patient prognosis as well as distinct immunity markers were analyzed in a total of 3011 breast cancer patients using TCGA, METABRIC and metastatic breast cancer (MBC) cohort GSE110590. Results: We established FHS, based on CD8A, GZMB and CXCL10 gene expression levels of bulk tumors, which delivered the best prognostic value among some gene combinations. Breast cancer patients with the high-FHS tumors showed significantly better survival. FHS was lower in the MBCs. Triple-negative breast cancer (TNBC) showed the highest FHS among subtypes. FHS predicted patient survival in hormone receptor (HR)-negative, especially in TNBC, but not in HR-positive breast cancer. FHS predicted patient prognosis independently in TNBC. The high-FHS TNBCs showed not only higher CD8+ T cell infiltration, but also enhanced broader type-1 anti-cancer immunity. The patients with the high-FHS tumors showed better prognosis not only in high-TMB tumors but also in low-TMB TNBCs. The combination of high-TMB with high-FHS identified a unique subset of patients who do not recur over time in TNBC. Conclusion: TNBCs with high FHS based on the expression levels of CD8A, GZMB and CXCL10 showed improved prognosis with enhanced anti-cancer immunity regardless of TMB. FHS constitutes an independent prognostic marker of survival, particularly robustly when combined with TMB in TNBC.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Manuela Fantini ◽  
Lorenzo Gianni ◽  
Carlotta Santelmo ◽  
Fabrizio Drudi ◽  
Cinzia Castellani ◽  
...  

The introduction of cisplatin in cancer treatment represents an important achievement in the oncologic field. Many types of cancers are now treated with this drug, and in testicular cancer patients major results are reached. Since 1965, other compounds were disovered and among them carboplatin and oxaliplatin are the main Cisplatin analogues showing similar clinical efficacy with a safer toxicity profile. Lipoplatin is a new liposomal cisplatin formulation which seems to have these characteristics. Lipoplatin was shown to be effective in NSCLC both in phase 2 and phase 3 trials, with the same response rate of Cisplatin, a comparable overall survival but less toxicity. A new protocol aiming to elucidate the double capacity of Lipoplatin to act as a chemotherapeutic and angiogenetic agent in triple-negative breast cancer patients is upcoming.


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