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Supplementary Table S1 from Secreted CXCL1 Is a Potential Mediator and Marker of the Tumor Invasion of Bladder Cancer

Purpose: The purpose of this study was to identify proteins that are potentially involved in the tumor invasion of bladder cancer.Experimental Design: We searched for the candidate proteins by comparing the profiles of secreted proteins among the poorly invasive human bladder carcinoma cell line RT112 and the highly invasive cell line T24. The proteins isolated from cell culture supernatants were identified by shotgun proteomics. We found that CXCL1 is related to the tumor invasion of bladder cancer cells. We also evaluated whether the amount of the chemokine CXCL1 in the urine would be a potential marker for predicting the existence of invasive bladder tumors.Results: Higher amount of CXCL1 was secreted from highly invasive bladder carcinoma cell lines and this chemokine modulated the invasive ability of those cells in vitro. It was revealed that CXCL1 regulated the expression of matrix metalloproteinase-13 in vitro and higher expression of CXCL1 was associated with higher pathologic stages in bladder cancer in vivo. We also showed that urinary CXCL1 levels were significantly higher in patients with invasive bladder cancer (pT1-4) than those with noninvasive pTa tumors (P = 0.0028) and normal control (P < 0.0001). Finally, it was shown that CXCL1 was an independent factor for predicting the bladder cancer with invasive phenotype.Conclusions: Our results suggest that CXCL1 modulates the invasive abilities of bladder cancer cells and this chemokine may be a potential candidate of urinary biomarker for invasive bladder cancer and a possible therapeutic target for preventing tumor invasion.

Genomic analysis of tumors is transforming our understanding of cancer. However, although a great deal of attention is paid to the accuracy of the cancer genomic data itself, less attention has been paid to the accuracy of the associated clinical information that renders the genomic data useful for research. In this brief communication, we suggest that omissions and errors in clinical annotations have a major impact on the interpretation of cancer genomic data. We describe our discovery of annotation omissions and errors when reviewing an already carefully annotated colorectal cancer gene expression dataset from our laboratory. The potential importance of clinical annotation omissions and errors was then explored using simulation analyses with an independent genomic dataset. We suggest that the completeness and veracity of clinical annotations accompanying cancer genomic data require renewed focus by the oncology research community, when planning new collections and when interpreting existing cancer genomic data.

Prediction of clinical behaviour and treatment for cancers is based on the integration of clinical and pathological parameters. Recent reports have demonstrated that gene expression profiling provides a powerful new approach for determining disease outcome. If clinical and microarray data each contain independent information then it should be possible to combine these datasets to gain more accurate prognostic information. Here, we have used existing clinical information and microarray data to generate a combined prognostic model for outcome prediction for diffuse large B-cell lymphoma (DLBCL). A prediction accuracy of 87.5% was achieved. This constitutes a significant improvement compared to the previously most accurate prognostic model with an accuracy of 77.6%. The model introduced here may be generally applicable to the combination of various types of molecular and clinical data for improving medical decision support systems and individualising patient care.

The work presented in this thesis was originally commenced as an investigation into the factors responsible for the selection of specific breeding places by various species of mosquitoes, particularly those occurring in salt water compared with certain fresh water species. At the same time it was realized that no satisfactory keys and only very imperfect descriptions of the larvae and larval habitats of Australian Culicines were available and an account was prepared (Paper No. 7) of some common species. Although this paper appears as a Joint publication, it is included in this thesis since it is essentially the work of the senior author, the Junior author's share being limited to the preparation of illustrations under the direction of the senior author.