3745 - Multi-level proteomics identifies FABP5 as a primary chemoresistance mediator in extensive-stage small cell lung cancer

Background

Small cell lung cancer (SCLC), a highly invasive neuroendocrine tumor, accounts for approximately 15% of all new diagnosed lung cancer. Primary disease is highly sensitive to chemotherapy as well as radiotherapy, recurrences occur quickly, and less effective to subsequent therapies than the initial chemotherapy, the response rate of second-line therapy topotecan is only 22%. Drug resistance, is the main reason for failure of SCLC chemotherapy. Here, we quantitatively analyzed the proteomes of Cisplatin/Etoposide-resistant and -sensitive ES-SCLC patients from minute amounts of formalin-fixed and paraffin-embedded (FFPE) tissues. FABP5 was identified to be related with primary chemosensitivity, and may be an important mediator of Cisplatin/Etoposide-induced cell death.

Methods

51 tissue samples were collected from ES-SCLC patients who underwent Cisplatin and Etoposide chemotherapy in Zhe Jiang Cancer Hospital from January 2015 to November 2017. The 51 cases included 23 chemosensitive patients and 28 chemoresistant patients. System-wide quantitative proteomics approach was applied on the cohort of chemo-resistant and -sensitive tissues, and label free protein quantification was performed. Realtime-PCR was performed to assess the mRNA expression in H69 and multi-drug resistant H69AR cells.

Results

A total of 4,485 proteins were identified and quantified, more than 50% proteins were 10-70KD, Proteins with a fold difference greater than 1.5 (up/down) and a P value (t test) less than 0.05 were considered differentially expressed proteins, few overall proteome changes across the two groups. Comparison of the two-group found that FABP5 was significantly decreased in drug-resistant patients. Consistent with the protein level in tumor tissues, FABP5 mRNA was down-regulated in H69AR cells. FABP5 expression strongly correlated with decreased disease-free survival and overall survival in ES-SCLC patients.

Conclusions

These data revealed FABP5 may serve as a potential biomarker for primary chemoresistance and prognostic factor for patients with ES-SCLC, which need further research.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Yamei Chen.

Funding

National Natural Science Foundation of China (grant numbers 81672972).

Disclosure

All authors have declared no conflicts of interest.