Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases

Abstract

The risk of distant recurrence in breast cancer patients is difficult to assess with current clinical and histopathological parameters, and no validated serum biomarkers currently exist. Using a recently developed recombinant antibody microarray platform containing 135 antibodies against 65 mainly immunoregulatory proteins, we screened 240 sera from 64 patients with primary breast cancer. This unique longitudinal sample material was collected from each patient between 0 and 36 mo after the primary operation. The velocity for each serum protein was determined by comparing the samples collected at the primary operation and then 3-6 mo later. A 21-protein signature was identified, using leave-one-out cross-validation together with a backward elimination strategy in a training cohort. This signature was tested and evaluated subsequently in an independent test cohort (prevalidation). The risk of developing distant recurrence after primary operation could be assessed for each patient, using her molecular portraits. The results from this prevalidation study showed that patients could be classified into highversus low-risk groups for developing metastatic breast cancer with a receiver operating characteristic area under the curve of 0.85. This risk assessment was not dependent on the type of adjuvant therapy received by the patients. Even more importantly, we demonstrated that this protein signature provided an added value compared with conventional clinical parameters. Consequently, we present here a candidate serum biomarker signature able to classify patients with primary breast cancer according to their risk of developing distant recurrence, with an accuracy outperforming current procedures.affinity proteomics | monitoring disease | prognosis | tumour relaps | malignancy

Inhibition of Adaptive Immunity by IL9 Can Be Disrupted to Achieve Rapid T-cell Sensitization and Rejection of Progressive Tumor Challenges

“…Investigators found an increase in serum levels of IL-9 over time in patients that later developed metastatic lesions, suggesting a relationship between IL-9 and tumor progression, or tumor load (23). …”

Identification of plasma protein profiles associated with risk groups of prostate cancer patients

“…To this end, we have designed and applied a recombinant antibody microarray targeting mainly immunoregulatory analytes [23, 24]. Previously we have demonstrated the potential of our array design for cancer diagnosis [27], evidence-based therapy selection [28], as well as predicting the risk for breast cancer recurrence [30]. In this discovery study, we have extended the range of applications, and indicated its potential use for risk group stratification in PC, clearly differentiating the two lowest versus the highest risk groups.…”

“…We have demonstrated that the platform could be used to identify candidate biomarker signatures for e.g. diagnosis, prognosis, classification, and for evidence-based therapy selection [27–30]. …”

ecancermedicalscience

“…We concur with Chechlinska’s argument that most cancer prognostic biomarker studies using modern technologies are methodologically flawed as they compare samples from cancer patients with those of healthy, inflammation-free people [20] or at best with those of patients with already metastasised tumours. In validation studies, it is important to determine whether the patient has dormant disease, and what type of mechanism is active, together with his or her systemic inflammatory response [21]. …”