Association of Pre- and Postoperative Plasma Levels of Transforming Growth Factor β1 and Interleukin 6 and Its Soluble Receptor with Prostate Cancer Progression

Reactive stroma initiates during early prostate cancer development and coevolves with prostate cancer progression. Previous studies have defined the key markers of reactive stroma and have established that reactive stroma biology influences prostate tumorigenesis and progression. The stem/progenitor cells of origin and the mechanisms that regulate their recruitment and activation to myofibroblasts or carcinoma-associated fibroblasts are essentially unknown. Key regulatory factors have been identified, including transforming growth factor β, interleukin-8, fibroblast growth factors, connective tissue growth factor, wingless homologs-Wnts, and stromal cell-derived factor-1, among others. The biology of reactive stroma in cancer is similar to the more predictable biology of the stroma compartment during wound repair at sites where the epithelial barrier function is breached and a stromal response is generated. The coevolution of reactive stroma and the biology of how reactive stroma–carcinoma interactions regulate cancer progression and metastasis are targets for new therapeutic approaches. Such approaches are strategically designed to inhibit cancer progression by uncoupling the reactive stroma niche.

Download Full-text

The Addition of Interleukin-6 Soluble Receptor and Transforming Growth Factor Beta1Improves a Preoperative Nomogram for Predicting Biochemical Progression in Patients With Clinically Localized Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2003.12.037 ◽

2003 ◽

Vol 21 (19) ◽

pp. 3573-3579 ◽

Cited By ~ 168

Author(s):

Michael W. Kattan ◽

Shahrokh F. Shariat ◽

Ben Andrews ◽

Kuichun Zhu ◽

Eduardo Canto ◽

...

Keyword(s):

Prostate Cancer ◽

Growth Factor ◽

Plasma Levels ◽

Transforming Growth Factor ◽

Clinical Stage ◽

Gleason Grade ◽

Soluble Receptor ◽

Concordance Index ◽

Psa Progression ◽

Biochemical Progression

Purpose: Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta1(TGF-β1).Patients and Methods: Between November 7, 1994 and December 22, 1997, 714 patients with stage cT1c to cT3a prostate cancer and no prior therapy were treated with radical prostatectomy at the Methodist Hospital, Houston TX. Plasma levels of IL6SR and TGF-β1were measured in banked preoperative plasma. With these data, a nomogram was developed to predict the probability of PSA progression within 5 years of surgery. The nomogram was validated with bootstrapping to assess its discrimination and calibration performance.Results: In the multivariable Cox model, PSA (P = .004), IL6SR (P < .001), TGF-β1(P < .001), primary Gleason grade (P < .002), and secondary Gleason grade (P = .029) were associated with PSA progression, whereas clinical stage (P = .696) was not. The nomogram seemed to be well calibrated and had a bootstrap-corrected area under the receiver operating characteristic curve (ie, concordance index) of 0.83. For comparison, a nomogram that omitted IL6SR and TGF-β1achieved a concordance index of only 0.75.Conclusion: We found that pretreatment plasma levels of IL6SR and TGF-β1improved the ability to predict biochemical progression by a prognostically substantial margin. A nomogram including the pretreatment levels of these molecular markers, along with standard clinical markers, has been developed and internally validated.

Download Full-text