Alaei Elmira, Farahani Najma, Orouei Sima, Alimohammadi Mina, Daneshi Salman, Mousavi Tahoora, Mahmoodieh Behnaz, Taheriazam Afshin, Rahimzadeh Payman, Hashemi Mehrdad
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Mol Cell Probes. 2025 Jun;81:102028. doi: 10.1016/j.mcp.2025.102028. Epub 2025 Mar 24.
CD44 is a promising target in the prognosis and treatment of non-small cell lung cancer (NSCLC). The study deals with systematic review and meta-analysis to determine the association between CD44 overexpression and survival and clinicopathological characteristics in NSCLC patients.
We used the databases Google Scholar, Web of Science, PubMed, Scopus, EMBASE, and Cochrane to conduct a systematic search of English-language literature published up to September 2023. The eligible studies were retrieved on CD44 expression, clinicopathological characteristics in NSCLC patients, and reported survival rates. The Cochran's and Higgins I tests were used to measure heterogeneity across the included studies. P < 0.05 was considered statistically significant in all cases. The sources of heterogeneity across the included studies were identified using subgroup analysis on histology (SCC, ADC, and LCC), tumor differentiation (well, moderate, and poor), TMN stage (I/II/III/IV), OS, and lymph node metastasis (negative and positive). All statistical analyses were carried out using meta-analysis (CMA) software.
The final analysis for prognostic significance and clinicopathological features on 3681 participants from 25 eligible studies. The pooled event rate of overexpression CD44 for overall survival in NSCLC was 38 % and was related to SCC with 76.6 %. Furthermore, subgroup analysis revealed a link between CD44 overexpression and moderate tumor differentiation (41.8 %). There was a substantial difference in CD44 overexpression in males, with 69.3 % (95 % CI: 64.3-73.9 %, I = 88.25 %) versus 31.5 % (95 % CI: 26.7-36.8 %, I = 92.15 %) in females. However, no significant relationship was observed between CD44 overexpression and TMN stages/lymph node metastasis.
The meta-analysis demonstrated that CD44 is an effective prognostic factor for NSCLC. Overexpression of CD44 has been linked to moderate tumor differentiation, SCC tumor histology, and a worse survival rate. However, no substantial relationship was found between CD44 and metastasis or TMN stages. Large-scale prospective research is required to validate CD44's clinical value as an unbiased prognostic indicator.
CD44是预测非小细胞肺癌（NSCLC）预后及指导治疗的一个有前景的靶点。本研究通过系统评价和荟萃分析，以确定CD44过表达与NSCLC患者生存率及临床病理特征之间的关联。
我们利用谷歌学术、科学网、PubMed、Scopus、EMBASE和Cochrane等数据库，对截至2023年9月发表的英文文献进行系统检索。检索符合条件的关于CD44表达、NSCLC患者临床病理特征及报告生存率的研究。采用Cochran's检验和Higgins I检验来衡量纳入研究之间的异质性。所有情况下，P < 0.05被认为具有统计学意义。通过对组织学（鳞状细胞癌、腺癌和大细胞癌）、肿瘤分化程度（高分化、中分化和低分化）、TMN分期（I/II/III/IV）、总生存期和淋巴结转移情况（阴性和阳性）进行亚组分析，确定纳入研究中异质性的来源。所有统计分析均使用荟萃分析（CMA）软件进行。
对来自25项符合条件研究的3681名参与者进行了预后意义和临床病理特征的最终分析。NSCLC患者总体生存中CD44过表达的合并事件发生率为38%，且与鳞状细胞癌相关，占76.6%。此外，亚组分析显示CD44过表达与肿瘤中分化（41.8%）之间存在关联。男性CD44过表达存在显著差异，男性为69.3%（95%CI：64.3 - 73.9%，I = 88.25%），女性为31.5%（95%CI：26.7 - 36.8%，I = 92.15%）。然而，未观察到CD44过表达与TMN分期/淋巴结转移之间存在显著关系。
荟萃分析表明，CD44是NSCLC的一个有效预后因素。CD44过表达与肿瘤中分化、鳞状细胞癌组织学类型及较差的生存率相关。然而，未发现CD44与转移或TMN分期之间存在显著关系。需要进行大规模前瞻性研究以验证CD44作为无偏倚预后指标的临床价值。
