Introduction/Background In our previous microarray study we identified a 96-gene prognostic signature associated with the shorter overall survival (OS) of ovarian cancer patients.1 Two genes from this signature, both coding for extracellular matrix proteins, were objects of the present study: FN1 and POSTN. We analyzed, by immunostaining, expression of encoded proteins in the independent set of ovarian cancer samples and evaluated its correlation with clinical, pathological, and molecular features.
Methodology Ovarian cancer samples from 108 patients were analyzed by immunochistochemistry using rabbit anti-human fibronectin polyclonal antibody (1:3000 dilution, A0245, Dako, Glostrup, USA) and rabbit anti-human periostin polyclonal antibody (1:200 dilution, ab14041, Abcam, Cambridge, UK). Correlation with survival was evaluated with Cox proportional-hazards model and Kaplan–Meier estimator with log-rank test. Two-sided p-values <0.05 were considered statistically significant. Analyses were carried out using Statistica 13.1 (TIBCO Software Inc., Palo Alto, CA, USA).
Results We observed that the higher expression of FN1 and POSTN was associated with shorter OS (log-rank: p-value 0.003 and 0.04 respectively). Next, we analyzed performance of the combined FN1&POSTN score calculated as a sum of individual FN1 and POSTN scores. We hypothesized that two-protein score would be more robust than evaluation of single proteins. Indeed, Cox regression demonstrated that FN1&POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02–4.60; p-value 0.044). However, we observed two outliers: out of the entire cohort one patient with a score 2 (indicating favorable prognosis) had the shortest OS and one patient with score 6 (indicating worst prognosis) had the second longest OS (131.17 month). These observations indicate that the FN1&POSTN score behaves similarly to classical prognostic factors: some patients having good prognosis, progress quickly and die early, while some patients with bad prognosis live unexpectedly long. In addition, our study showed that expression of fibronectin and periostin was associated with the source of OC sample: metastases showed higher expression of these proteins than primary tumors (chi2 test, p-value 0.024 and p-value 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers.
Conclusion In summary, we found that the joint FN1&POSTN score is an independent prognostic factor for OS in ovarian cancer patients.2 Moreover, our results support the role of the cancer microenvironment in tumor progression and prognosis and add to the concept that some ovarian cancers originate from fallopian tube epithelium.
Disclosures Authors have nothing to disclose.
Lisowska KM, et al. (2016), DOI:10.1007/s00432-016-2147-y
Kujawa KA, et al. (2019), DOI:10.3390/cells9010149
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