Identification and clinical implications of circulating cancer associated fibroblasts in lung cancer patients

Abstract

Objectives

In tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) are known to expedite cancer progression (metastasis). CAF-secreted cytokines confer a survival advantage to circulating tumor stem cells (CTSCs) (indicators of residual-disease) facilitating immune system evasion. Collectively, CAFs serve as “bio-incubator" by providing favourable "soil" for their subsequent growth in the circulation during EMT and are thus considered as an important target in diagnostic and therapeutic applications. Thus, the aim of this study was to check the presence of circulating CAF (cCAFs) in blood of lung cancer patients as a liquid biopsy approach.

Materials and methods

Mononuclear cells isolated from the peripheral blood of non-metastatic lung cancer patients were cultured to confirm the presence of cCAF. CAF-specific marker α-SMA and FAP was used to characterise them using Western blot and real time PCR. Furthermore, correlation between expression of cCAFs and various clinico-pathological parameters were examined.

Results

Cultured MNCs showed the presence of cCAFs which was further confirmed by western blotting. All patients were found positive for the presence of cCAFs (α-SMA expression), while healthy individuals lacked this, being α-SMA negative. Moreover, significant trend was observed between different stages of lung cancer patients (p < 0.014), suggesting its probable role in lung cancer progression.

Conclusion

Thus, cCAFs could be companion biomarker for the early detection of tumors as well as it could be efficient biomarker for the prediction of metastasis. However, validation of cCAFs as robust marker is still required to be tested in a more number of patients. This should be done using more than one marker associated with CAFs for their clinical application, as it has a potential implication to monitor the effectiveness of a specific cancer therapy and disease progression.