Pi Yingqi, Lin Sizhuo, Ren Xiuqin, Wang Lin, Song Yiling, Wu Zhikun, Lai Yanzhen
Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Clinical Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Front Oncol. 2024 Feb 13;14:1337707. doi: 10.3389/fonc.2024.1337707. eCollection 2024.
The identification of effective tumor markers is of paramount importance for the early diagnosis, treatment, and prognosis of esophageal squamous cell carcinoma (ESCC). The present study endeavors to identify efficacious serological markers that can differentiate patients with early-stage ESCC from those with benign esophageal lesions and healthy controls (HC). Cystatin-SN (CST1), an active cysteine protease inhibitor belonging to the Cystatin (CST) superfamily, is implicated in the pathogenesis of inflammation and tumorigenesis. The objective of this investigation is to assess the diagnostic, therapeutic, and prognostic potential of serum CST1 in ESCC.
In our prior RNA sequencing and screening endeavors, we have identified ten genes that are up-regulated in relation to esophageal cancer. Subsequently, we have verified the gene CST1 from the transcriptome data of the The Cancer Genome Atlas Program (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) database. Following this, we conducted an enzyme-linked immunosorbent assay (ELISA) to ascertain the expression levels of CST1 in serum samples from clinical cohorts.
The study revealed a significant elevation in serum CST1 levels among patients with early-stage esophageal squamous cell carcinoma (ESCC) (7.41 ± 4.32 ng/ml) compared to those with esophageal benign lesions (4.67 ± 2.43 ng/ml) (p < 0.0001) and healthy controls (4.87 ± 2.77 ng/ml) (p < 0.0001). The diagnostic sensitivity of CST1 for ESCC was 75.68% (specificity 70.83%, AUC 0.775). Combination of CST1 and SCC-Ag exhibited the AUC up to 0.819. Additionally, serum CST1 levels exhibited a significant decrease at 1-2 weeks post-surgery (4.49 ± 3.31 ng/ml) compared to pre-surgery levels (7.68 ± 3.71 ng/ml) (p<0.0001). Survival analysis demonstrated a strong association between high (844/415-1543 d) or low (1490/645-1710 d) serum CST1 levels at diagnosis and overall survival time (p < 0.001). Furthermore, multivariate regression analysis confirmed CST1 (p=0.024, HR=2.023, 95%CI 1.099-3.725) as an independent prognostic factor.
Serum CST1 has the potential to function as a diagnostic indicator for distinguishing early-stage esophageal squamous cell carcinoma (ESCC) from individuals with benign esophageal lesions and healthy individuals. Additionally, it could serve as a prognostic predictor and therapeutic efficacy indicator for patients with ESCC.
有效肿瘤标志物的鉴定对于食管鳞状细胞癌（ESCC）的早期诊断、治疗及预后至关重要。本研究致力于鉴定能区分早期ESCC患者与食管良性病变患者及健康对照（HC）的有效血清学标志物。胱抑素 - SN（CST1）是一种属于胱抑素（CST）超家族的活性半胱氨酸蛋白酶抑制剂，与炎症发病机制及肿瘤发生有关。本研究的目的是评估血清CST1在ESCC中的诊断、治疗及预后潜力。
在我们之前的RNA测序和筛选工作中，我们鉴定出了10个与食管癌相关的上调基因。随后，我们从癌症基因组图谱计划（TCGA）和基因表达谱交互式分析（GEPIA）数据库的转录组数据中验证了基因CST1。在此之后，我们进行了酶联免疫吸附测定（ELISA），以确定临床队列血清样本中CST1的表达水平。
研究显示，早期食管鳞状细胞癌（ESCC）患者血清CST1水平（7.41±4.32 ng/ml）显著高于食管良性病变患者（4.67±2.43 ng/ml）（p<0.0001）和健康对照（4.87±2.77 ng/ml）（p<0.0001）。CST1对ESCC的诊断敏感性为75.68%（特异性70.83%，AUC 0.775）。CST1与鳞状细胞癌抗原（SCC - Ag）联合检测时AUC高达0.819。此外，与术前水平（7.68±3.71 ng/ml）相比，术后1 - 2周血清CST1水平显著下降（4.49±3.31 ng/ml）（p<0.0001）。生存分析表明，诊断时血清CST1水平高（844/415 - 1543天）或低（1490/645 - 1710天）与总生存时间密切相关（p<0.001）。此外，多因素回归分析证实CST1（p = 0.024，HR = 2.023，95%CI 1.099 - 3.725）是一个独立的预后因素。
血清CST1有潜力作为诊断指标，用于区分早期食管鳞状细胞癌（ESCC）患者与食管良性病变个体及健康个体。此外，它还可作为ESCC患者的预后预测指标和治疗疗效指标。
