The present invention relates to the prediction of the survival time of a patient suffering from a cancer. The inventors identified in blood from healthy donors a subpopulation of WIT cells that expresses CD73 and displays immunosuppressive phenotype and functions (i.e., production of immunosuppressive molecules and inhibition of αßT cell proliferation). Furthermore, they detected the presence of CD73+ γδ T cells in immune infiltrates of freshly resected breast cancer specimens. Altogether, these data suggest that part of γδ T cells infiltrated in the breast cancer microenvironment presents a regulatory phenotype characterized by CD73 expression, and are likely to display pro-tumor functions through the mechanisms they described in vitro. Thus, the invention relates to a method for predicting the survival time of a patient suffering from a cancer comprising i) determining in a sample obtained from the patient the level of Gamma/Delta T cells expressing CD73 ii) comparing the expression level determined at step i) with its predetermined reference value and iii) providing a good prognosis when the level of Gamma/Delta T cells expressing CD73 determined at step i) is lower than its predetermined reference value, or providing a bad prognosis when the level of Gamma/Delta T cells expressing CD73 determined at step i) is higher than its predetermined reference value.

Methods for measuring subpopulations of target molecules (e.g., polypeptides and/or cell-free ribonucleic acid) are provided. In some embodiments, methods of generating a sequencing library from a plurality of RNA molecules in a test sample obtained from a subject are provided, as well as methods for analyzing the sequencing library to detect, e.g., the presence or absence of a disease.

Methods for treating and/or prognosing breast cancer and breast cancer recurrence are provided. The method includes obtaining a tissue sample of a tumor from a breast cancer patient, determining an expression level of one or more markers (for example PD-1 and/or PD-L1) in the sample, and providing intensified treatment to the subject based on the level of (for example) PD-1 and/or PD-L1. The intensified treatment can be intensified radiotherapy treatment.

Embodiments of the instant disclosure relate to novel methods and compositions for distinguishing high-grade ductal carcinoma in situ (DCIS) from lower-grade DCIS in a breast tissue. Other embodiments of the instant disclosure provide for methods of administering one or more appropriate breast cancer treatment regimens to a subject diagnosed with high-risk DCIS.

Cancer patients make antibodies to tumor-derived proteins that are potential biomarkers for early detection. Twenty-eight antigens have been identified as potential biomarkers for the early detection of basal-like breast cancer (Tables 1, 2). Also, a 13-AAb classifier has been developed that differentiate patients with BLBC from healthy controls with 33% sensitivity at 98% specificity (Table 3).

From gene expression analysis with a long-term recurrence-free group and a recurrence metastasis group of stomach cancer, CHRNB2 and NPTXR were identified as drug discovery targets. Tumor growth was successfully inhibited by an antibody medicine or a nucleic acid medicine targeting CHRNB2 or NPTXR. Furthermore, a polyclonal antibody and a monoclonal antibody linking to CHRNB2 or NPTXR are provided. Since these receptor molecules are novel molecular targets, treatment of cases which the existing therapeutic drugs have no effect on is made possible.

The state of protein phosphorylation and glycosylation can be key determinants of cellular physiology such as early stage cancer, but the development of phosphoproteins and/or glycoproteins in biofluids for disease diagnosis remains elusive. Here we demonstrate, for the first time, a strategy to isolate and identify phosphoproteins/glycoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs by isolating from small volume of plasma samples. Using label-free quantitative phosphoproteomics, we identified 144 phosphoproteins in plasma EVs that are significantly higher in patients diagnosed with breast cancer than in healthy controls. Several novel biomarkers were validated in individual patients using Paralleled Reaction Monitoring for targeted quantitation. Similarly a group of glycoproteins in plasma EVs are identified. The study demonstrated that the development of phosphoproteins and/or glycoproteins in plasma EV as disease biomarkers is highly feasible and may transform cancer screening and monitoring.

The present invention refers to the use of synthetic peptides built from the selection of peptides available on the surface of filamentous phages and that bind to the FabC4 antibody fragment with clinical relevance in the diagnosis of Breast Cancer (BC) and in the prognosis of Triple-Negative Breast Cancer (TNBC). The peptides were specific to tumor proteins and could be potentially used in immunodiagnostic tests, formulations coupled to fluorescent or radioactive particles for diagnostic imaging, therapeutic drug carriers, and in immunogenic compositions for BC management. The technology used for peptide selection was the peptide expression system on the surface of filamentous bacteriophage. The strategy used was the selection of binding peptides of tumor proteins present in serum from TNBC patients.

The invention is directed to methods of treating TNBC in a patient by administering to the patient an agent that inhibits the expression or activity of cyclin-dependent kinase 19 (CDK19). In some embodiments, the agent may be a small molecule inhibitor, a polynucleotide (e.g., shRNA. siRNA), or a protein (e.g., an antibody). In some embodiments, the agent does not inhibit the activity or expression of CDK8.

This disclosure is directed, in part, to a method of determining whether a subject having cancer is at risk for developing metastasis of the cancer. In one embodiment, the method comprises (a) obtaining a biological sample from the subject having cancer; (b) determining CCR5 expression level and/or expression level of at least one of CCR5 ligands in the biological sample; and (c) if the expression level of CCR5 and/or of at least one of CCR5 ligands determined in step (b) is increased compared to CCR5 expression level and/or expression level of at least one of CCR5 ligands in a control sample, then the subject is identified as likely at risk for developing metastasis of the cancer.