Sun Hui, Zhang Weigang, Chu Yunqian, Zhou Lei, Gong Feiran, Li Wei, Chen Kai
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
J Gastrointest Oncol. 2023 Jun 30;14(3):1525-1545. doi: 10.21037/jgo-23-308. Epub 2023 Jun 19.
The incidence and mortality of pancreatic cancer are almost the same, and the 5-year survival rate is less than 10%. The high mortality of pancreatic cancer is related to chemo-radiotherapy. The present study aimed to establish a prognostic signature of pancreatic cancer based on chemo-radiotherapy resistant-related genes (CRRGs).
In this study, we explored the radiation-resistant and chemotherapy-resistant pancreatic cancer cell lines by colony formation and a subcutaneous tumor model in nude mice. Next, we obtained CRRGs from radiation- and gemcitabine-resistant pancreatic cancer cell lines in the Gene Expression Omnibus (GEO) database. Based on univariate Cox and least absolute shrinkage and selection operator (LASSO) Cox regression analyses, a prognostic model of the pancreatic adenocarcinoma (PAAD) cohort in The Cancer Genome Atlas (TCGA) database (N=177) was established and verified using the GEO cohort data set (N=112). Finally, the functions of candidate target genes were verified by a methyl thiazolyl tetrazolium (MTT) assay, a colony formation assay, and a subcutaneous tumor model in nude mice.
Through the and experiments, we found that radiotherapy- and chemotherapy-resistant pancreatic cancer cells were cross-resistant to chemotherapy and radiotherapy. We constructed a risk model consisting of nine CRRGs (, , , , , , , , and ) by using public databases. According to the Kaplan-Meier curve analysis, the survival of the high-risk group was worse than that of the low-risk group. We then used nomograms to predict the 1/3/5-year overall survival (OS) in pancreatic cancer patients. We chose as a candidate target since it has been proven to be involved in the stemness maintenance of cancer cells, and found that silencing inhibited the proliferation and chemo-radiotherapy tolerance of pancreatic cancer cells.
This study established and validated a prognostic signature of pancreatic cancer using nine CRRGs. The and experiments showed that could promote the proliferation and chemoradiotherapy tolerance of pancreatic cancer cell lines. These findings may offer new insights into the role of CRRGs in pancreatic cancer and provide novel prognostic biomarkers for the treatment of pancreatic cancer.
胰腺癌的发病率和死亡率几乎相同，5年生存率低于10%。胰腺癌的高死亡率与放化疗有关。本研究旨在基于放化疗抗性相关基因（CRRGs）建立胰腺癌的预后特征。
在本研究中，我们通过集落形成和裸鼠皮下肿瘤模型探索了抗辐射和抗化疗的胰腺癌细胞系。接下来，我们从基因表达综合数据库（GEO）中抗辐射和吉西他滨抗性的胰腺癌细胞系中获得CRRGs。基于单变量Cox和最小绝对收缩和选择算子（LASSO）Cox回归分析，建立了癌症基因组图谱（TCGA）数据库（N = 177）中胰腺腺癌（PAAD）队列的预后模型，并使用GEO队列数据集（N = 112）进行验证。最后，通过甲基噻唑基四氮唑（MTT）试验、集落形成试验和裸鼠皮下肿瘤模型验证了候选靶基因的功能。
通过实验，我们发现放疗和化疗抗性的胰腺癌细胞对化疗和放疗具有交叉抗性。我们利用公共数据库构建了一个由9个CRRGs（、、、、、、、、和）组成的风险模型。根据Kaplan-Meier曲线分析，高危组的生存率低于低危组。然后，我们使用列线图预测胰腺癌患者的1/3/5年总生存率（OS）。我们选择作为候选靶标，因为它已被证明参与癌细胞的干性维持，并发现沉默可抑制胰腺癌细胞的增殖和放化疗耐受性。
本研究使用9个CRRGs建立并验证了胰腺癌的预后特征。实验表明可促进胰腺癌细胞系的增殖和放化疗耐受性。这些发现可能为CRRGs在胰腺癌中的作用提供新的见解，并为胰腺癌的治疗提供新的预后生物标志物。
