BACKGROUND The heat-shock transcription factor 1 (HSF1) has been linked to cell proliferation and survival in cancer and has been proposed as a biomarker for poor prognosis. Here, we assessed the role of HSF1 expression in relation to copy number alteration (CNA) and cancer prognosis. METHODS Using 10,287 cancer genomes from The Cancer Genome Atlas and Cbioportal databases, we assessed the association of HSF1 expression with CNA and cancer prognosis. CNA of 8q24.3 was categorized as diploid (reference), deletion (fewer copies), gain (+ 1 copy) and amplification (≥ + 2 copies). Multivariate logistic regression modeling was used to assess 5-year survival among those with a first cancer diagnosis and complete follow-up data (N = 9568), categorized per anatomical location and histology, assessing interaction with tumor stage, and expressed as odds ratios and 95% confidence intervals. RESULTS We found that only 54.1% of all tumors have a normal predicted 8q24.3 copy number and that 8q24.3 located genes including HSF1 are mainly overexpressed due to increased copies number of 8q24.3 in different cancers. The tumor of patients having respectively gain (+ 1 copy) and amplification (≥ + 2 copies) of 8q24.3 display a global increase of 5-year mortality (odds ratio = 1.98, 95% CI 1.22-3.21) and (OR = 2.19, 1.13-4.26) after full adjustment. For separate cancer types, tumor patients with 8q24.3 deletion showed a marked increase of 5-year mortality in uterine (OR = 4.84, [2.75-8.51]), colorectal (OR = 4.12, [1.15-14.82]), and ovarian (OR = 1.83, [1.39-2.41]) cancers; and decreased mortality in kidney cancer (OR = 0.41, [0.21-0.82]). Gain of 8q24.3 resulted in significant mortality changes in 5-year mortality for cancer of the uterus (OR = 3.67, [2.03-6.66]), lung (OR = 1.76, [1.24-2.51]), colorectal (OR = 1.75, [1.32-2.31]) cancers; and amplification for uterine (OR = 4.58, [1.43-14.65]), prostate (OR = 4.41 [3.41-5.71]), head and neck (OR = 2.68, [2.17-3.30]), and stomach (OR = 0.56, [0.36-0.87]) cancers. CONCLUSIONS Here, we show that CNAs of 8q24.3 genes, including HSF1, are tightly linked to 8q24.3 copy number in tumor patients and can affect patient outcome. Our results indicate that the integration of 8q24.3 CNA detection may be a useful predictor for cancer prognosis.

中文翻译：

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8q24.3的拷贝数驱动HSF1表达和癌症患者的预后：一项单独的患者数据荟萃分析。

背景技术热休克转录因子1（HSF1）与癌症中的细胞增殖和存活有关，并已被提议作为预后不良的生物标志物。在这里，我们评估了HSF1表达在拷贝数改变（CNA）和癌症预后方面的作用。方法使用来自癌症基因组图谱和Cbioportal数据库的10287个癌症基因组，我们评估了HSF1表达与CNA和癌症预后的关系。8q24.3的CNA分为二倍体（参考），缺失（较少拷贝），获得（+1个拷贝）和扩增（≥+ 2个拷贝）。多因素Logistic回归模型用于评估首次诊断为癌症且具有完整随访数据（N = 9568）的患者的5年生存率，按解剖位置和组织学分类，评估与肿瘤分期的相互作用，并表示为优势比和95％置信区间。结果我们发现，只有54.1％的肿瘤具有正常的预测8q24.3拷贝数，而位于8q24.3的基因（包括HSF1）主要由于不同癌症中8q24.3的拷贝数增加而过表达。分别获得（+1个拷贝）和扩增（≥+ 2个拷贝）的8q24.3患者的肿瘤显示5年死亡率的整体增加（优势比= 1.98，95％CI 1.22-3.21）和（OR = 2.19，1.13-4.26）。对于单独的癌症类型，具有8q24.3缺失的肿瘤患者显示子宫（OR = 4.84，[2.75-8.51]），结直肠癌（OR = 4.12，[1.15-14.82]）和卵巢的5年死亡率显着增加（OR = 1.83，[1.39-2.41]）癌症；并降低了肾癌的死亡率（OR = 0.41，[0.21-0.82]）。获得8q24。3导致子宫癌（OR = 3.67，[2.03-6.66]），肺癌（OR = 1.76，[1.24-2.51]），结直肠癌（OR = 1.75，[1.32- 2.31]）癌症；子宫（OR = 4.58，[1.43-14.65]），前列腺（OR = 4.41 [3.41-5.71]），头颈部（OR = 2.68，[2.17-3.30]）和胃（OR = 0.56， [0.36-0.87]）癌症。结论在这里，我们显示了包括HSF1在内的8q24.3基因的CNA与8q24.3拷贝数在肿瘤患者中紧密相关，并且可以影响患者的预后。我们的结果表明，8q24.3 CNA检测的整合可能是癌症预后的有用预测指标。前列腺癌（OR = 4.41 [3.41-5.71]），头颈癌（OR = 2.68，[2.17-3.30]）和胃癌（OR = 0.56，[0.36-0.87]）。结论在这里，我们显示了包括HSF1在内的8q24.3基因的CNA与8q24.3拷贝数在肿瘤患者中紧密相关，并且可以影响患者的预后。我们的结果表明，8q24.3 CNA检测的整合可能是癌症预后的有用预测指标。前列腺癌（OR = 4.41 [3.41-5.71]），头颈部癌（OR = 2.68，[2.17-3.30]）和胃癌（OR = 0.56，[0.36-0.87]）。结论在此，我们显示了包括HSF1在内的8q24.3基因的CNA与8q24.3拷贝数在肿瘤患者中紧密相关，并且可以影响患者的预后。我们的结果表明，8q24.3 CNA检测的整合可能是癌症预后的有用预测指标。