Three Biomarkers Identified from Serum Proteomic Analysis for the Detection of Early Stage Ovarian Cancer

Abstract

Early detection remains the most promising approach to improve long-term survival of patients with ovarian cancer. In a five-center casecontrol study, serum proteomic expressions were analyzed on 153 patients with invasive epithelial ovarian cancer, 42 with other ovarian cancers, 166 with benign pelvic masses, and 142 healthy women. Data from patients with early stage ovarian cancer and healthy women at two centers were analyzed independently and the results cross-validated to discover potential biomarkers. The results were validated using the samples from two of the remaining centers. After protein identification, biomarkers for which an immunoassay was available were tested on samples from the fifth center, which included 41 healthy women, 41 patients with ovarian cancer, and 20 each with breast, colon, and prostate cancers. Three biomarkers were identified as follows: (a) apolipoprotein A1 (down-regulated in cancer); (b) a truncated form of transthyretin (down-regulated); and (c) a cleavage fragment of inter-␣-trypsin inhibitor heavy chain H4 (up-regulated). In independent validation to detect early stage invasive epithelial ovarian cancer from healthy controls, the sensitivity of a multivariate model combining the three biomarkers and CA125 [74% (95% CI, 52-90%)] was higher than that of CA125 alone [65% (95% CI, 43-84%)] at a matched specificity of 97% (95% CI, 89 -100%). When compared at a fixed sensitivity of 83% (95% CI, 61-95%), the specificity of the model [94% (95% CI, 85-98%)] was significantly better than that of CA125 alone [52% (95% CI, 39 -65%)]. These biomarkers demonstrated the potential to improve the detection of early stage ovarian cancer.

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy

“…The pooled coefficient of variance (pCV) for peak intensity was calculated for each experimental condition and had a mean of 22% (12-35%), in agreement with previous reports (Petricoin et al, 2002a, b;Koopmann et al, 2004;Zhang et al, 2004).…”

“…Interestingly, some of the identified biomarkers in our study were found to be modulated by various cancer diseases in other serum-based proteomic studies. Thus, haptoglobin was found upregulated in serum of ovarian, oesophageal and small-cell lung cancer patients (Steel et al, 2003;Ahmed et al, 2004;Bharti et al, 2004), while complement C3 and apolipoprotein A1 (Steel et al, 2003;Zhang et al, 2004) were found downmodulated in liver or ovarian cancer. However, these studies were dedicated to the identification of serum biomarkers associated to cancer diagnosis, rather than prediction of clinical outcome.…”

“…Rather than diluted, low level tumor-specific proteins, SELDIanalysis could detect more abundant but specifically tumor-processed host-response proteins (Paradis et al, 2004;Zhang et al, 2004). These issues will benefit from purification and identification of the other contributors to the multiprotein index that are currently ongoing.…”

“…Consequently, serum may be an appropriate surrogate tissue to investigate since it may share the fingerprint of various physiologic or pathologic processes involving cancer tissue and/or host response (Fung et al, 2005). Coupled to appropriate bioinformatic tools, SELDI-TOF MS was recently shown as a very promising method for probing serum to identify protein patterns and/or biomarkers related to various stages and types of solid tumors (Adam et al, 2002a;Petricoin et al, 2002a, b;Koopmann et al, 2004;Wadsworth et al, 2004;Zhang et al, 2004), which could serve as early diagnostic markers.…”

Enzymes and related proteins as cancer biomarkers: A proteomic approach

“…In our biomarker study in ovarian cancer, serum was collected and proteomic expressions were analyzed from a patient population consist of >500 patients with invasive epithelial ovarian cancer, benign pelvic masses and healthy controls from 5 separate cancer institutes [18]. Data from patients with early stage ovarian cancer and healthy women at 2 centers were analyzed independently and the results cross-validated to discover potential biomarkers.…”