The clinicopathologic and prognostic value of CD44 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis

Background: 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. Methods: 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 I2 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. Results: 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-2 = 88.25 %) versus 31.5 % (95 % CI: 26.7-36.8 %, I-2 = 92.15 %) in females. However, no significant relationship was observed between CD44 overexpression and TMN stages/ lymph node metastasis. Conclusion: 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.