Dataset Information

Examination of Independent Prognostic Power of Gene Expressions and Histopathological Imaging Features in Cancer.

ABSTRACT: Cancer prognosis is of essential interest, and extensive research has been conducted searching for biomarkers with prognostic power. Recent studies have shown that both omics profiles and histopathological imaging features have prognostic power. There are also studies exploring integrating the two types of measurements for prognosis modeling. However, there is a lack of study rigorously examining whether omics measurements have independent prognostic power conditional on histopathological imaging features, and vice versa. In this article, we adopt a rigorous statistical testing framework and test whether an individual gene expression measurement can improve prognosis modeling conditional on high-dimensional imaging features, and a parallel analysis is conducted reversing the roles of gene expressions and imaging features. In the analysis of The Cancer Genome Atlas (TCGA) lung adenocarcinoma and liver hepatocellular carcinoma data, it is found that multiple individual genes, conditional on imaging features, can lead to significant improvement in prognosis modeling; however, individual imaging features, conditional on gene expressions, only offer limited prognostic power. Being among the first to examine the independent prognostic power, this study may assist better understanding the "connectedness" between omics profiles and histopathological imaging features and provide important insights for data integration in cancer modeling.

SUBMITTER: Zhong T

PROVIDER: S-EPMC6468814 | biostudies-other | 2019 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Examination of Independent Prognostic Power of Gene Expressions and Histopathological Imaging Features in Cancer.

Zhong Tingyan T Wu Mengyun M Ma Shuangge S

Cancers 20190313 3

Cancer prognosis is of essential interest, and extensive research has been conducted searching for biomarkers with prognostic power. Recent studies have shown that both omics profiles and histopathological imaging features have prognostic power. There are also studies exploring integrating the two types of measurements for prognosis modeling. However, there is a lack of study rigorously examining whether omics measurements have independent prognostic power conditional on histopathological imagin ...[more]

PMID: 30871256

Similar Datasets

Project description:BackgroundIncidental hepatocellular carcinoma (iHCC) is a histological finding after liver transplantation (LT) which relevance has been scarcely studied.Aimsto describe the histopathological features of iHCC and to determine its prognostic impact in terms of tumor recurrence and overall survival.MethodsObservational study including 451 consecutive adult LT patients (2000-2013). Patients aged<18, retransplanted or with early postoperative death were excluded. Median follow-up after LT was 58 months. Multiple Cox's regression was used to assess the prognostic impact of iHCC on tumor recurrence and mortality while controlling for potential confounders.Results141 patients had known HCC before LT (31.3%). Among the remaining 310 patients, the prevalence of iHCC was 8.7% (n = 27). In the explanted liver, 36.2% of patients with known HCC and 25.9% of patients with iHCC trespassed Milan criteria (p = 0.30). Patients with known and iHCC had similar rates of multinodular disease (50.4% vs 55.6%; p = 0.62), macrovascular invasion (6.5% vs 3.7%; p = 0.58), microvascular invasion (12.9% vs 14.8%; p = 0.76) and moderate-poor tumor differentiation (53.9% vs 70.4%; p = 0.09). In the multivariate analysis, iHCC and known HCC had identical recurrence-free survival after controlling for histological features (RR = 1.06, 95%CI 0.36-3.14; p = 0.90). Cumulative 5-year overall survival rates were similar between patients with known and iHCC (65% vs 52.8% respectively; log rank p = 0.44), but significantly inferior as compared with patients without HCC (77.8%) (p = 0.002 and p = 0.007 respectively). Indeed, in the overall cohort, iHCC was an independent predictor of mortality (RR = 3.02; 95%CI 1.62-5.65; p = 0.001).ConclusionThe risk of tumor recurrence after LT is similar in patients with iHCC and known HCC. A close imaging surveillance is strongly recommended for patients awaiting LT in order to detect HCC prior to LT, thus allowing for an adequate selection of candidates, prioritization and indication of bridging therapies.

Project description:PURPOSE:For optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk. METHODS:Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS?±?RT) using Krippendorff's alpha (KA) and Gwet's AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression. RESULTS:Interrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2?+?3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05-6.11); grade 3 versus 1?+?2 (HR 2.64, 95% CI 1.35-5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34-10.23) were independently associated with a higher iIBC risk. CONCLUSIONS:Using majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features.

Project description:Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT-TYR, ATRT-MYC and ATRT-SHH. ATRT-SHH represents the largest molecular group and is heterogeneous with regard to age, tumor location and epigenetic profile. We, therefore, aimed to investigate if heterogeneity within ATRT-SHH might also have biological and clinical importance. Consensus clustering of DNA methylation profiles and confirmatory t-SNE analysis of 65 ATRT-SHH yielded three robust molecular subgroups, i.e., SHH-1A, SHH-1B and SHH-2. These subgroups differed by median age of onset (SHH-1A: 18 months, SHH-1B: 107 months, SHH-2: 13 months) and tumor location (SHH-1A: 88% supratentorial; SHH-1B: 85% supratentorial; SHH-2: 93% infratentorial, often extending to the pineal region). Subgroups showed comparable SMARCB1 mutational profiles, but pathogenic/likely pathogenic SMARCB1 germline variants were over-represented in SHH-2 (63%) as compared to SHH-1A (20%) and SHH-1B (0%). Protein expression of proneural marker ASCL1 (enriched in SHH-1B) and glial markers OLIG2 and GFAP (absent in SHH-2) as well as global mRNA expression patterns differed, but all subgroups were characterized by overexpression of SHH as well as Notch pathway members. In a Drosophila model, knockdown of Snr1 (the fly homologue of SMARCB1) in hedgehog activated cells not only altered hedgehog signaling, but also caused aberrant Notch signaling and formation of tumor-like structures. Finally, on survival analysis, molecular subgroup and age of onset (but not ASCL1 staining status) were independently associated with overall survival, older patients (> 3 years) harboring SHH-1B experiencing relatively favorable outcome. In conclusion, ATRT-SHH comprises three subgroups characterized by SHH and Notch pathway activation, but divergent molecular and clinical features. Our data suggest that molecular subgrouping of ATRT-SHH has prognostic relevance and might aid to stratify patients within future clinical trials.

Dataset Information

Examination of Independent Prognostic Power of Gene Expressions and Histopathological Imaging Features in Cancer.

Publications

Examination of Independent Prognostic Power of Gene Expressions and Histopathological Imaging Features in Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets