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Poster display session

14P - Up-regulated PI3K/mTOR/AKT pathway behind the downregulation of PTEN, FBXW7, genes and miRNA 140-145, ALK mediated chemotherapy resistance in non-small cell lung carcinoma (NSCLC)

Date

15 Oct 2022

Session

Poster display session

Presenters

Muhammad Jawad Aslam

Citation

Annals of Oncology (2022) 33 (suppl_8): S1383-S1430. 10.1016/annonc/annonc1095

Authors

M.J. Aslam1, M.N. Faisal1, H. Nazeer1, J. Hussain2, H. Muzaffar3, A. Mahmood4, H. Javed1, Q. Tanveer5

Author affiliations

  • 1 University of Agriculture, Faisalabad, Faisalabad/PK
  • 2 University of Copenhagen, Copenhagen/DK
  • 3 GCUF - Government College University Faisalabad, Faisalabad/PK
  • 4 Islamiyah University Bahawalpur, Bahawalpur/PK
  • 5 University of Edinburgh, Edinburgh/GB
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Abstract 14P

Background

Tumor cells have a tendency to proliferate rapidly and can metastasize to other organs of the body. Respiratory carcinomas are among 3rd predominant causes of cancer-related deaths in both genders around the globe. Type of epithelial lung cancer non-small cell lung carcinoma (NSCLC) constitutes 80% of all lung cancer types. The 5-year survival rate of NSCLC is about 16%. This Study was conducted to understand the chemoresistance through expression of proto-onco genes (AKT1, ALK), onco-suppressive (FBXW7, PTEN) genes and their correlation with miRNA 140-145 in NSCLC.

Methods

Bronchoscopy of lung cancer patients who were on different medications was conducted for collection of samples from regional health care facility under the guidelines of ethical review committee. Samples were subjected to histopathology and for further processing to carry out RNA extraction and gene expression studies through qRT-PCR/ gel-electrophoresis. The data was analyzed statistically through one-way ANOVA for analysis of variance and DMR.

Results

It has been revealed that the expression level of proto-onco ALK and AKT1 genes is significantly higher in lung cancer patients in comparison to normal ones (P<0.05). PTEN and FBXW7 are onco-suppressive genes, so these genes are downregulated after mutational changes in lung parenchyma of cancer patient samples (P<0.05). Correlation of PTEN and AKT1 genes revealed that upregulation of PTEN gene down express the AKT1 gene through PI3K/AKT/mTOR signaling pathway. Relatively higher expression of miRNA 140-145 disrupt the function of c-Myc and Cyclin-E proteins which is the thought to be the reason behind chemoresistance in NSCLC patients (P<0.05). Histopathological examination showed neoplastic cellular proliferation without infiltration into dermal areas in lung cancer tissue but in control, there is uniform cellular structure.

Conclusions

This study concludes that perturbation in miRNA 140-145 mediate post transcriptional activation of proto-onco genes through PI3k/ AKT pathway and hence contribute towards chemoresistance in 2nd-3rd grade NSCLC patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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