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Abstract：
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.
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.
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.
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.
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.
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.
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.
摘要：
热休克转录因子1（HSF1）与癌症中的细胞增殖和存活有关，并已被提议作为不良预后的生物标志物。这里,我们评估了HSF1表达与拷贝数改变(CNA)和癌症预后的关系.
使用来自癌症基因组图谱和Cbioportal数据库的10,287个癌症基因组，我们评估了HSF1表达与CNA和癌症预后的相关性.8q24.3的CNA被归类为二倍体（参考），删除（更少的副本），增益（+1个拷贝）和扩增（≥+2个拷贝）。多变量逻辑回归模型用于评估首次诊断癌症和完整随访数据的患者的5年生存率（N=9568）。按解剖位置和组织学分类，评估与肿瘤分期的相互作用，并表示为比值比和95%置信区间。
我们发现，只有54.1%的肿瘤具有正常的预测8q24.3拷贝数，并且由于不同癌症中8q24.3拷贝数的增加，包括HSF1在内的8q24.3定位基因主要过表达。分别具有8q24.3的增益（1个拷贝）和扩增（≥2个拷贝）的患者的肿瘤显示出5年死亡率的全球增加（比值比=1.98，95％CI1.22-3.21）和（OR=2.19，1.13-4.26）。对于不同的癌症类型，8q24.3缺失的肿瘤患者子宫5年死亡率明显增加(OR=4.84,[2.75-8.51]),结直肠（OR=4.12，[1.15-14.82]），和卵巢癌(OR=1.83,[1.39-2.41]);肾癌死亡率降低(OR=0.41,[0.21-0.82])。8q24.3的增益导致子宫癌5年死亡率的显着变化（OR=3.67，[2.03-6.66]），肺（OR=1.76，[1.24-2.51]），结直肠癌（OR=1.75，[1.32-2.31]）；子宫癌放大（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]），和胃癌（OR=0.56，[0.36-0.87]）。
这里,我们显示8q24.3基因的CNA，包括HSF1，与肿瘤患者的8q24.3拷贝数密切相关，并可能影响患者的预后。我们的结果表明，8q24.3CNA检测的整合可能是癌症预后的有用预测因子。
使用来自癌症基因组图谱和Cbioportal数据库的10,287个癌症基因组，我们评估了HSF1表达与CNA和癌症预后的相关性.8q24.3的CNA被归类为二倍体（参考），删除（更少的副本），增益（+1个拷贝）和扩增（≥+2个拷贝）。多变量逻辑回归模型用于评估首次诊断癌症和完整随访数据的患者的5年生存率（N=9568）。按解剖位置和组织学分类，评估与肿瘤分期的相互作用，并表示为比值比和95%置信区间。
我们发现，只有54.1%的肿瘤具有正常的预测8q24.3拷贝数，并且由于不同癌症中8q24.3拷贝数的增加，包括HSF1在内的8q24.3定位基因主要过表达。分别具有8q24.3的增益（1个拷贝）和扩增（≥2个拷贝）的患者的肿瘤显示出5年死亡率的全球增加（比值比=1.98，95％CI1.22-3.21）和（OR=2.19，1.13-4.26）。对于不同的癌症类型，8q24.3缺失的肿瘤患者子宫5年死亡率明显增加(OR=4.84,[2.75-8.51]),结直肠（OR=4.12，[1.15-14.82]），和卵巢癌(OR=1.83,[1.39-2.41]);肾癌死亡率降低(OR=0.41,[0.21-0.82])。8q24.3的增益导致子宫癌5年死亡率的显着变化（OR=3.67，[2.03-6.66]），肺（OR=1.76，[1.24-2.51]），结直肠癌（OR=1.75，[1.32-2.31]）；子宫癌放大（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]），和胃癌（OR=0.56，[0.36-0.87]）。
这里,我们显示8q24.3基因的CNA，包括HSF1，与肿瘤患者的8q24.3拷贝数密切相关，并可能影响患者的预后。我们的结果表明，8q24.3CNA检测的整合可能是癌症预后的有用预测因子。
