Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Department of Clinical Laboratory, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China.
Sci Rep. 2024 Sep 28;14(1):22517. doi: 10.1038/s41598-024-73847-1.
PANoptosis is engaged in the program of immune response and carcinogenicity. Nonetheless, the actual impacts of PANoptosis on clinical management and oncology immunity in hepatocellular carcinoma (HCC) are not fully grasped. RNA-seq-derived computations were conducted to sort out the molecular subtypes and elucidate the disparities based on PANoptosis molecules. Single-cell sequencing (scRNA-seq) tools including Cytotrace and Addmodulescore were extracted to characterize diversification potency and quantify the PANoptosis motion. Transcriptional factors were inferred by the pySCENIC package and Cellchat program scrutinized the intercellular exchange across cell compartments. The PANoptosis score system originated by incorporating 10 machine learning algorithms and 101 compositions to project clinical results and deteriorate tendencies. Circulatory PANoptosis-associated protein HSP90AA1 was determined by enzyme-linked immunosorbent assay (ELISA). HCC individuals could be categorized into low- and high-PANoptosis groups with diverse biogenic and pharmacotherapy heterogeneity. Individuals in the elevated PANoptosis subtype were characterized as "hot tumor" conveying the increased presence of immunogenicity while reiterating an explicit negative connection with tumor stemness. Compared to immune and stromal cells, cancerous cells showcased decreased PANoptosis and heightened PANoptosis malignant cell subgroups might be tied to a substantial level of genomic expression of SREBF2, JUND, GATAD1, ZBTB20, SMAD5 and implied a more aggressive potential. The PANoptosis index, derived from machine learning, has been established to provide succinct frameworks for predicting outcomes and clarified the noteworthy utility of conventional regimens, as the differentiated power of HCC occurred together with vascular invasion and hepatocellular adenoma (HCA). The experiment confirmed that the circulating HSP90AA1 was aberrantly augmented in HCC patients, thus demonstrating its potential as a discriminatory biomarker. We systematically deciphered the molecular and immune ecosystem traits of PANoptosis in bulk and scRNA-seq degrees, which may deliver advantageous insights for customized treatment, awareness of the pathological process and prognosis scrutiny for HCC patients.
细胞焦亡参与免疫反应和致癌作用。然而,细胞焦亡对肝细胞癌(HCC)的临床管理和肿瘤免疫的实际影响尚未完全被理解。通过 RNA 测序衍生的计算,对分子亚型进行了分类,并根据细胞焦亡分子阐明了差异。提取了单细胞测序(scRNA-seq)工具,包括 Cytotrace 和 Addmodule score,以描绘多样化能力,并量化细胞焦亡运动。通过 pySCENIC 包推断转录因子,并通过 Cellchat 程序研究细胞区室之间的细胞间交换。通过整合 10 种机器学习算法和 101 种成分,提出了细胞焦亡评分系统,以预测临床结果和恶化趋势。通过酶联免疫吸附试验(ELISA)测定循环细胞焦亡相关蛋白 HSP90AA1。HCC 患者可以分为低细胞焦亡和高细胞焦亡组,具有不同的生物发生和药物治疗异质性。升高的细胞焦亡亚型中的个体表现为“热肿瘤”,具有更高的免疫原性,同时与肿瘤干性呈明显负相关。与免疫细胞和基质细胞相比,癌细胞的细胞焦亡减少,而恶性细胞亚群的细胞焦亡增加可能与 SREBF2、JUND、GATAD1、ZBTB20、SMAD5 的基因组表达水平显著相关,并暗示了更具侵袭性的潜力。从机器学习中得出的细胞焦亡指数已被建立,为预测结果提供了简洁的框架,并阐明了传统方案的显著实用性,因为 HCC 的分化能力与血管侵犯和肝细胞腺瘤(HCA)有关。实验证实,HCC 患者的循环 HSP90AA1 异常升高,因此证明其作为一种有潜力的鉴别生物标志物。我们系统地解析了细胞焦亡在批量和 scRNA-seq 水平上的分子和免疫生态系统特征,这可能为 HCC 患者的个体化治疗、对病理过程的认识和预后评估提供有益的见解。