Prognostic impact of CD34 and SMA in cancer‐associated fibroblasts in stage I–III NSCLC

Abstract

BackgroundEpithelial‐to‐mesenchymal transition (EMT) is a crucial step in lung cancer pathogenesis. Among others, cancer‐associated fibroblasts (CAFs) are reported to regulate this process.ObjectivesTo investigate the prognostic and clinical impact, we analyzed CD34+ and SMA+ CAFs in non‐small cell lung cancer (NSCLC).MethodsRetrospectively, immunohistochemistry was performed to study stromal protein expression of both CD34 and SMA in 304 NSCLC patients with pTNM stage I‐III disease. All tissue samples were embedded on tissue microarrays (TMAs).ResultsOur analysis revealed an association for CD34+ CAFs with G1/2 tumors and adenocarcinoma histology. Moreover CD34+ CAFs were identified as an independent prognostic factor (both for progression free survival [PFS] and overall survival [OS] in stage I‐III NSCLC). Besides, SMA+ expression correlated with higher pTNM‐tumor stages and lymphatic spread (pN stage). In turn, SMA‐negativity was associated with improved PFS, but no prognostic impact was found on OS. Of interest, neither CD34+ CAFs nor SMA+ CAFs were associated with the primary tumor size, localization and depth of infiltration (pT stage).ConclusionsCD34 was identified as an independent prognostic marker in pTNM stage I‐III NSCLC. Moreover, loss of CD34+ CAFs might influence the dedifferentiation of the NSCLC tumor from its cell origin. Finally, SMA+ CAFs are more prevalent in NSCLC tumors of higher stages and lymphonodal positive NSCLC.Key points Expression of CD34 on cancer associated fibroblasts (CAFs) is an independent prognostic factor in stage I‐III NSCLC.SMA+ cancer associated fibroblasts are associated with higher tumor stages in NSCLC and might contribute to tumor progression in NSCLC.

IL17A critically shapes the transcriptional program of fibroblasts in pancreatic cancer and switches on their protumorigenic functions

“…Notably, the expression of Cd34 by IL17A -/cells only suggested the hematopoietic origin of these fibroblasts, which, however, also expressed higher or similar levels of genes usually associated with a fibroblast phenotype (Acta2, Postn, Pdgfrb, Col1a1, Col5, Col4a1 and Col4a2). Of note, the loss of CD34 on stromal cells has been associated with the increased ability of breast cancer cells to invade surrounding tissues and metastasize (30), and has been defined as an independent prognostic factor in non-small cell lung cancer stage I-III (31). Interestingly, IL17A +/+ CAFs also highly expressed Anxa6 and Areg, which were almost absent in IL17A -/-CAFs.…”

CD34+ Stromal Cells/Telocytes as a Source of Cancer-Associated Fibroblasts (CAFs) in Invasive Lobular Carcinoma of the Breast

“…Future studies should also cover the co-localization of CD34 with other fibroblastic markers due to fibroblastic heterogeneity [ 52 ], including fibronectin, which promotes the eventual acquisition of a fibrotic response, and TGF β1, which activates the fibroinflammatory genomic program [ 53 , 54 , 55 , 56 ]. Likewise, the investigation of the origin of CAFs from CD34 + SCs/TCs should extend to tumors from other tissue locations (e.g., prostate, lung or skin), for which data that indicate this possibility have been provided [ 57 , 58 , 59 ].…”

Role of cancer‑associated fibroblasts in the resistance to antitumor therapy, and their potential therapeutic mechanisms in non‑small cell lung cancer (Review)

“…Tissue analysis revealed a high mortality rate among 220 patients with NSCLC and high α-SMA expression, indicating that α-SMA is associated with poor survival time ( 56 ). Immunohistochemical analysis of 304 patients with pTNM stage I–III NSCLC revealed that CAF-associated CD34 expression was an independent prognostic factor for stage I–III NSCLC, and that SMA+CAFs were associated with higher tumor stages and promoted tumor progression ( 57 ). The 28 patients with NSCLC were divided into two CAF subgroups, the high desmoplastic CAFs (HD-CAFs) and low desmoplastic CAFs (LD-CAFs), according to the obtained scores and classification based on desmoplasia.…”