The proteolysis-inducing factor: in search of its clinical relevance in patients with metastatic gastric/esophageal cancer

Abstract

The proteolysis-inducing factor is a putative mediator of cancer-associated weight loss. The goal of this study was to examine for the first time: (i) its prevalence in patients with metastatic gastric/esophageal cancer; and (ii) whether it possibly correlated with weight loss and anorexia and whether it predicted tumor response and patient survival. This study recruited 41 patients as part of a phase II therapeutic, chemotherapy protocol for patients with metastatic gastric/esophageal cancer. Patient eligibility criteria were designed to select a group of patients who would tolerate treatment with the drugs capecitabine and oxaliplatin. Urine for assaying the proteolysis-inducing factor was obtained at registration and then 6 weeks later. Patients completed the FACT-E questionnaire every 6 weeks and had their weights checked at the same interval. Patients were followed prospectively for tumor response and patient survival. Twenty-three (56%) patients had the proteolysis-inducing factor in their urine at registration, and 18 (64%) had it at 6 weeks. There was no statistically significant correlation between the presence of the proteolysis-inducing factor and weight loss or between its presence and anorexia. Moreover, there was no evidence that the presence of the proteolysis-inducing factor in urine was able to predict tumor response or patient survival. The proteolysis-inducing factor in urine does not appear to be tied to weight loss, anorexia, tumor response, or patient survival in the clinical setting of metastatic gastric/esophageal cancer.

Individualized Chemotherapy for Metastatic Gastric Cancer: Retrospective Data from a University Hospital in Brazil

“…A phase III study reported 47.9% objective response for patients treated with EOX; this difference in outcomes may be explained by the difference in number of patients treated in each study (16 and 244, respectively) (Cunningham et al, 2008). Some phase II studies that evaluated the efficacy of treatment with two drugs reported an overall RR of 42% on average (range: 35% to 65%) that is consistent with the value obtained in this study (Jatoi et al, 2006;Park et al, 2006;Van Meerten et al, 2007). This study was not designed to compare various treatment protocols, so these findings must be analyzed carefully.…”

Is There a Human Homologue to the Murine Proteolysis-Inducing Factor?

“…Additionally, mRNA encoding the PIF core peptide was reported recently in nonmalignant tissue (12). The Western blot signal using PIF mAb had no relationship with survival in our or other studies (10,11). This is an important discrepancy because weight loss predicts survival, especially in cancers of the lung (26 -28) and esophagus (29).…”

“…The gastric/esophageal patients did not show a relationship between PIF status and weight loss (11). Weight data are not available on all the lung patients, but for 116 of them, there are a total of 970 individual weight records extractable from patient charts or on average 8.3 weight records per patient.…”

“…Additionally, PIF was absent in cancer patients without weight loss or weight-losing patients with benign disease (7). These results suggested discovery of a critical factor underlying human cancer cachexia, but attempts at further confirmation suggested that PIF was not necessarily associated with clinical outcomes (i.e., survival and weight loss) in cancer patient populations (11,12).…”

“…Additionally, PIF was absent in cancer patients without weight loss or weight-losing patients with benign disease (7). These results suggested discovery of a critical factor underlying human cancer cachexia, but attempts at further confirmation suggested that PIF was not necessarily associated with clinical outcomes (i.e., survival and weight loss) in cancer patient populations (11,12).Regulation of expression of the human PIF core peptide, the sites at which glycosylation occurs to form the functional glycoprotein, and the structure of the oligosaccharides (5, 7), which confer the proteolysis-inducing activity to this unusual molecule, remain unresolved. A peptide sequence (7) and two patents describing the human cachexia-associated protein (HCAP) gene encoding PIF were published (Genbank accession no.…”