ABSTRACT
Background: In non-small cell lung cancer common driver mutations such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are usually mutually exclusive. This study aimed to elucidate the concurrence of EGFR mutation and ALK rearrangement in eastern India patients with primary lung adenocarcinoma and assess the response of EGFR tyrosine kinase inhibitor (TKI) therapy after 6 months in primary lung adenocarcinoma. Methods: We retrospectively analyzed 198 adenocarcinomas for EGFR and ALK mutations. EGFR and ALK tests were done by real-time polymerase chain reaction and immunohistochemistry (IHC) techniques, respectively. Radiological response was assessed by Response Evaluation Criteria in Solid Tumors (version 1.1). Results: EGFR/ALK co-alteration was found in 4 adenocarcinoma patients. All were males with advanced disease. Younger patients had exon 19 deletion whereas older ones showed exon 21 mutation. The initial option of ALK-TKI in all four patients was excluded straightaway due to the high-cost burden of ALK-TKI. Two of them showed a partial response while other two had stable disease after 6 months of EGFR TKI therapy. Conclusion: EGFR/ALK co-alterations in adenocarcinomas albeit rare do exist. The challenge of monetary hurdle in developing countries with ALK TKI therapy can be handled by giving only EGFR TKI in these cases of concomitant mutations. Future perspective in research could be finding an agent with the potential of dual inhibition of ALK and EGFR
ABSTRACT
Objective To explore the protective effect of long non-coding RNA(lncRNA) metasta-sis associated in lung denocarcinoma transcript 1 (MALAT1) involved in hyperoxia-induced lung injury in preterm infants.Methods This study had downloaded chip data set GSE25286 (Mouse GEO Genome 430 2.0 Array) from gene expression database gene expression omnibus (GEO),according to the state of hyperoxia exposure,the MALAT1 mRNA expression in rats normal lung tissues and hyperoxic lung tissues was compared at day 14th and 29th.In chip data set GSE43830(Human Exon 1.0 ST Arrays) from GEO,the expression of multi-ple genes[cell division cycle 6(CDC6),death effector domain containing 2(DEDD2),and Cyclin B1 (CCNB1)] in WI38 cells(lung fibroblasts) was compared before and after MALAT1 was knockout.At the same time,the peripheral blood samples of premature infants were collected to verify.Totally 40 premature infants were hospitalized in the department of neonatology in our hospital from Jan 2015 to Dec 2016,the pe-ripheral blood samples of 40 premature infants were collected.RNA was extracted and Real time-PCR was performed after reverse transcription,clinical data of these 40 cases were retrospectively analyzed. Results (1) By using Affymetrix Expression console and Affymetrix Transcriptome analysis console software source files of the chip of pretreatment and difference expression gene screening,the expression of lncRNA MALAT1 gene in lung tissues of hyperoxia lung injury mice significantly upregulated[fold change(FC) =2.33,P=0.001].(2) After MALAT1 in WI38 cell was knockout,MALAT1 expression was significantly reduced(FC= -15.6,P=0.000),the expression of CDC6(FC= -2.37,P=0.001) and CCNB1(FC=-2.16,P=0.002) were down regulated,DEDD2 expression was up regulated(FC =2.46,P =0.000). (3) The results of peripheral blood samples from preterm infants showed that the expression of MALAT1 was significantly increased in preterm infants with hyperoxia-induced lung injury(0.375 5 ± 0.081 9,t =4.634, P=0.015),compared with normal preterm infants(0.273 4 ± 0.067 3).Conclusion Through inhibiting cell apoptosis,lncRNA MALAT1 can protect preterm infants with hyperoxia-induced lung injury,it may provide a new strategy for prevention and treatment of hyperoxia-induced lung injury in premature infants.