| Literature DB >> 28291248 |
Qing Zhong1, Tiannan Guo2, Markus Rechsteiner1, Jan H Rüschoff1, Niels Rupp1, Christian Fankhauser3, Karim Saba3, Ashkan Mortezavi3, Cédric Poyet3, Thomas Hermanns3, Yi Zhu2, Holger Moch1, Ruedi Aebersold2,4, Peter J Wild1,5.
Abstract
Microscopy image data of human cancers provide detailed phenotypes of spatially and morphologically intact tissues at single-cell resolution, thus complementing large-scale molecular analyses, e.g., next generation sequencing or proteomic profiling. Here we describe a high-resolution tissue microarray (TMA) image dataset from a cohort of 71 prostate tissue samples, which was hybridized with bright-field dual colour chromogenic and silver in situ hybridization probes for the tumour suppressor gene PTEN. These tissue samples were digitized and supplemented with expert annotations, clinical information, statistical models of PTEN genetic status, and computer source codes. For validation, we constructed an additional TMA dataset for 424 prostate tissues, hybridized with FISH probes for PTEN, and performed survival analysis on a subset of 339 radical prostatectomy specimens with overall, disease-specific and recurrence-free survival (maximum 167 months). For application, we further produced 6,036 image patches derived from two whole slides. Our curated collection of prostate cancer data sets provides reuse potential for both biomedical and computational studies.Entities:
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Year: 2017 PMID: 28291248 PMCID: PMC5349242 DOI: 10.1038/sdata.2017.14
Source DB: PubMed Journal: Sci Data ISSN: 2052-4463 Impact factor: 6.444
Figure 1Sample tissue cores of matching H&E images, DISH images, and signal colour maps.
Six examples of H&E images (top row), DISH images (middle row), and signal colour maps (bottom row) with patient-level expert annotations, such as tissue types and PTEN genetic status. Signal colour maps can be generated by our ISHProfiler software. For the signal colour maps, black signals indicate the PTEN gene, red signals indicate the CEP10, and green signal indicate the mixed classes PTEN+CEP10. CRPC, castration resistant prostate cancer; LNM, lymph node metastases; RPE, radical prostatectomy.
Summary of DISH images, PTEN genetic status, clinical information and survival data of patient cohorts with prostate cancer.
| Prostate cancer TMA ( | DISH staining and digitization by Zeiss | Manual assessment | Computational analysis (Matlab codes) | Comparison with FISH and patient-level annotation | Data Citation 1 |
| Prostate cancer TMA ( | DISH and H&E staining and digitization by Hamamatsu | Manual assessment | Computational analysis (Matlab codes) | Comparison with FISH and patient-level annotation | Data Citation 2 |
| Prostate cancer ( | FISH staining, collection of clinical and survival data | Manual assessment | Kaplan-Meier estimator (R codes) | Univariate and multivariate Cox regression | Data Citation 3 |
| Prostate cancer and two whole slide images ( | DISH staining and digitization | NA | Computational analysis | Post visual inspection | Data Citation 4 |
| Prostate cancer TMA ( | DISH and H&E staining and digitization by Hamamatsu | NA | NA | Output.ndpi file format | Data Citation 5 |
Summary of clinical and survival data.
| TMA | References the ‘Loc’ variable in demo1.xlsx (ISHProfiler®) (e.g., A_1_1) |
| rfs | Recurrence-free survival (0–163 months) |
| st_rfs | Status for recurrence-free survival (0: censored, 1: recurrence, 3: never reached nadir) |
| os | Overall survival (0–167months) |
| st_os_gen | Status for overall survival (0: censored, 1: any death) |
| st_os_spec | Status for disease-specific survival (0: censored, 1: death from prostate cancer) |
| tiss | Tissue type (1: RPE, 2: CRPC, 3: LNM, 4: DM, 8: BPH) |
| age_d64 | Age at RPE (dichotomization by 64) (0<64 years, 1≥64 years) |
| BMI_d25 | Body mass index (dichotomization by 25) (0≤25 kgm−2, 1>25 kgm−2) |
| GLE_t | Gleason score (1: Gleason score 5–6, 2: 7, 3: 8–10) |
| pT_t | Tumour stage (1: pT2, 2: pT3, 3: pT4) |
| pN | Nodal status (0: no tumour, 1: positive surgical margin) |
| R1 | Surgical margin status (0: R0, 1: R1) |
| PSA_d10 | PSA at diagnosis (dichotomization by 10) (0<10 ngml−1, 1≥10 ngml−1) |
| PTEN_cyt | PTEN IHC (cytoplasmic intensity) (0: negative, 1: weak, 2: moderate, 3: strong) |
| SPOP | SPOP mutation FD (0: wild-type, 1: mutated) |
| ERG | ERG break-apart FISH (0: FISH−, 1: FISH+) |
| PTEN_FISH_ratio | PTEN FISH ratio (0.28–1.00) |
| PTEN_FISH_ratio_d60 | PTEN FISH ratio (dichotomization by 0.6) (0: no deletion (>0.6), 1: PTEN deletion (≤0.6)) |
| PTEN_FISH_percent_ab_nucl | PTEN FISH % aberrant nuclei (0–1.00) |
| PTEN_FISH_percent_d60 | PTEN FISH % aberrant nuclei (dichotomization by 0.6) (0: no deletion (<60%), 1: PTEN deletion (≥60%)) |
| PTEN_total_signals | Total PTEN FISH signals (10–123) |
| nuclei_number | Number of nuclei analysed (9–40) |
| CEP10_total_signals | Total CEP10 FISH signals (17–127) |
Figure 2Survival analysis of 339 RPE patients.
Kaplan-Meier curves with simultaneous 95% confidence bands of patient overall survival over time after diagnosis. Vertical lines illustrate patients who were censored at the time of their last clinical follow-up visit. Differences between survival estimates were evaluated by the log-rank test. N values represent the number of patients in each group under risk. For P-value, P<0.05 is marked in bold. (a) Kaplan-Meier curves for patients who were dichotomized into two groups by the percentage aberrant nuclei. (b) Kaplan-Meier curves for patients who were dichotomized into two groups by the ratio. (c) Overall survival hazard ratios by Cox regression. The dashed vertical line was drawn at the no effect point (hazard ratio of 1.0). Horizontal lines represent a 95% confidence interval (CI). The mid-point of the box represents the mean effect estimate and the area of the box represents the weight for each subgroup. Limit for the stepwise reverse selection procedure was P=0.1.