CD3D and PRKCQ work together to discriminate between B-cell and T-cell acute lymphoblastic leukemia
COMPUTERS IN BIOLOGY AND MEDICINE
Authors: Ma, Dongli; Zhong, Shan; Liu, Xiaorong; Mai, Huirong; Mai, Guoqin; Xu, Cheng; Zhou, Fengfeng
Abstract
Different therapeutic methods have been developed for the B-cell and T-cell subtypes of acute lymphoblastic leukemia (ALL). The identification of molecular biomarkers that can accurately discriminate between B-cell and T-cell ALLs will facilitate the quick determination of therapeutic plans, as well as reveal the intrinsic mechanisms underlining the two different ALL subtypes. This study computationally screened the high-throughput transcriptome dataset for multiple candidate biomarkers and verified their discrimination abilities in an independent sample set using quantitative real-time polymerase chain reaction (PCR) technology. Both technologies suggest that the two genes CD3D and PKRCQ together provided a good model for classification of B-cell and T-cell ALLs, whereas the individual genes did not show consistent discrimination between the two ALL subtypes. Supplementary material is available at http://healthinformaticslab.org/supp/. (C) 2016 Elsevier Ltd. All rights reserved.
Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer
JOURNAL OF CLINICAL ONCOLOGY
Authors: Denkert, Carsten; Loibl, Sibylle; Noske, Aurelia; Roller, Marc; Mueller, Berit Maria; Komor, Martina; Budczies, Jan; Darb-Esfahani, Silvia; Kronenwett, Ralf; Hanusch, Claus; von Toerne, Christian; Weichert, Wilko; Engels, Knut; Solbach, Christine; Schrader, Iris; Dietel, Manfred; von Minckwitz, Gunter
Abstract
Purpose Preclinical data suggest a contribution of the immune system to chemotherapy response. In this study, we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy. Methods We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies (GeparDuo, n = 218, training cohort; and GeparTrio, n = 840, validation cohort). Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed, paraffin-embedded tumor samples. Results In a multivariate regression analysis including all known predictive clinicopathologic factors, the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response (pCR) in both cohorts (training cohort: P = .012; validation cohort: P = .001). Lymphocyte-predominant breast cancer responded, with pCR rates of 42% (training cohort) and 40% (validation cohort). In contrast, those tumors without any infiltrating lymphocytes had pCR rates of 3% (training cohort) and 7% (validation cohort). The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate, and logistic regression showed a significant association of the T-cell-related markers CD3D and CXCL9 with pCR. Conclusion The presence of tumor-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy and provides useful information for oncologists to identify a subgroup of patients with a high benefit from this type of chemotherapy.