## 5 Conclusions  
In conclusion, based on TNMplot and UALCAN datasets, we found that _KRAS_ and _HRAS_ genes were highly expressed (upregulated) at the mRNA level in lung cancer tissue. Overexpression of the studied genes in NSCLC was associated with cancer stage, smoking habits, age, sex and nodal metastasis status. FTS, as a compound competing with active RAS form, inhibited the proliferation of human NSCLC cells A549 by inhibiting cell growth dependent on the RAS signaling pathway. Admittedly, its efficacy has not been confirmed in clinical trials, but it is still worth further investigation. Moreover, deltarasin, which downregulates RAS protein activity, reduced _HRAS_ expression level in A549. These preliminary in vitro findings need further studies on larger groups and other cell lines to better understand the molecular mechanisms of FTS and deltarasin on tumor cell activity. It may be possible that deltarasin or FTS might exert an antiproliferative effect applied in combination with other inhibitors in vitro and in vivo on lung cancer cell lines. Our findings also indicate that the RAS signaling pathway might be an attractive subject for further evaluation as a possible diagnostic or therapeutic goal in NSCLC on both the DNA and mRNA levels. To sum up, the results obtained from analyses based on bioinformatics databases indicate that the studied genes are potential risk factors for the development of lung cancer. On the other hand, studies of their expression on cell lines indicate that they may also be potentially important in the response to treatment using RAS inhibitors. The following supporting information can be downloaded at: [[https://www.mdpi.com/article/10.3390/app13010166/s1](https://www.mdpi.com/article/10.3390/app13010166/s1)]([https://www.mdpi.com/article/10.3390/app13010166/s1](https://www.mdpi.com/article/10.3390/app13010166/s1)), Table S1. Statistical significance of _KRAS_ and _HRAS_ expression levels in patients with NSCLC for all figures from UALCAN and TNMplot databases; Figure S1. The chemical structures of the of the three RAS inhibitors: deltarasin (A), famesvlthiosalicylic acid (B), Kobe0065 (C); Figure S2. An examples of the amplification curve plots for _GAPDH_ (A), _HRAS_ (B) and _KRAS_ (C) genes including NTC and the melting curves of the real-time PCR amplification products of the _GAPDH_ (D), _HRAS_ (E) and _KRAS_ (F) genes expressed as--ARFU/AT vs. temperature; Figure S3. The examples of standard curve plots for _GAPDH_, _KRAS_ and _HRAS_. (x-axis: log10 concentration of PCR product; y-axis--Ct values). Conceptualization, M.P. and E.B. ; validation, M.P. ; formal analysis, M.P., J.P. and M.Z.-N.; investigation, M.P., J.P., A.W. and M.Z.-N.; resources, E.B. ; writing--original draft preparation, M.P. and A.W. ; writing--review and editing M.Z.-N., M.P. and E.B. ; visualization, M.P. ; supervision, E.B. ; project administration, M.P. and E.B. ; funding acquisition, E.B. All authors have read and agreed to the published version of the manuscript. This research was funded by statutory funds of the Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, no: 503/3-015-02/503-31-001. * _[PERSON] et al. (2022)_ [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; et al. FDA Approval Summary: Sotorasib for _KRAS G12C_-Mutated Metastatic NSCLC. _Clin. Cancer Res._**2022**, _28_, 1482-1486. [CrossRef] [PubMed]
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