<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Cancer stem cells may be responsible for tumour regrowth and acquisition of resistance in small cell lung cancer (SCLC). The Hedgehog pathway regulates survival and proliferation of tissue progenitor and stem cell populations, promoting the expression of stem cell related and proliferative genes. We evaluated the Sonic Hedgehog (Shh) embryonic signalling pathway in relapsed SCLC. Expression levels of Shh related genes GLI1, SMO, SUFU, PTCH1, HHIP, BCL2, BMI, ZEB1, ZEB2, N-MYC, Twist1 were analysed by qRT-PCR in matched pre-treatment and relapsed tumour fresh frozen biopsies of three SCLC patients. Expression of each gene was compared using the paired samples t-test, as well as comparison of mean expression levels was done. Data were statistically interpreted using the MedCalc version 10.2.0.0 software. 2.9-fold lower mean mRNA expression of the major Hedgehog activation indicator GLI1 was observed in relapsed samples (p = 0.0529). Mean expression of six Shh inducible genes, PTCH1, HHIP, N-MYC, ZEB2, Twist1, ZEB1, was also downregulated by 2.6-, 2.2-, 1.9-, 1.8-, 1.2-, 1.1-fold, respectively (p = 0.4252, p = 0.1268, p = 0.2480, p = 0.1169, p = 0.1480, p = 0.7595, respectively). 1.8-fold mean expression decrease was found for Gli activator Smo (p = 0.4111). Only the Shh pathway inhibitor SUFU and two other examined Hedgehog signalling inducible genes BCL2 and BMI in relapsed SCLC showed 0.8-, 0.9-,and 0.8-fold increase of expression, respectively (p = 0.3074, p = 0.7921, and p = 0.3822, respectively). To our knowledge, this is the first report of comparison of Shh signalling in matched pre-treatment and relapsed SCLC biopsies. Our data show decreased activity for majority of Shh pathway components in relapsed SCLC, although difference did not reach statistical significance.</p>
</abstract>

Cancer stem cells may be responsible for tumour regrowth and acquisition of resistance in small cell lung cancer (SCLC). The Hedgehog pathway regulates survival and proliferation of tissue progenitor and stem cell populations, promoting the expression of stem cell related and proliferative genes. We evaluated the Sonic Hedgehog (Shh) embryonic signalling pathway in relapsed SCLC. Expression levels of Shh related genes GLI1, SMO, SUFU, PTCH1, HHIP, BCL2, BMI, ZEB1, ZEB2, N-MYC, Twist1 were analysed by qRT-PCR in matched pre-treatment and relapsed tumour fresh frozen biopsies of three SCLC patients. Expression of each gene was compared using the paired samples t-test, as well as comparison of mean expression levels was done. Data were statistically interpreted using the MedCalc version 10.2.0.0 software. 2.9-fold lower mean mRNA expression of the major Hedgehog activation indicator GLI1 was observed in relapsed samples (p = 0.0529). Mean expression of six Shh inducible genes, PTCH1, HHIP, N-MYC, ZEB2, Twist1, ZEB1, was also downregulated by 2.6-, 2.2-, 1.9-, 1.8-, 1.2-, 1.1-fold, respectively (p = 0.4252, p = 0.1268, p = 0.2480, p = 0.1169, p = 0.1480, p = 0.7595, respectively). 1.8-fold mean expression decrease was found for Gli activator Smo (p = 0.4111). Only the Shh pathway inhibitor SUFU and two other examined Hedgehog signalling inducible genes BCL2 and BMI in relapsed SCLC showed 0.8-, 0.9-,and 0.8-fold increase of expression, respectively (p = 0.3074, p = 0.7921, and p = 0.3822, respectively). To our knowledge, this is the first report of comparison of Shh signalling in matched pre-treatment and relapsed SCLC biopsies. Our data show decreased activity for majority of Shh pathway components in relapsed SCLC, although difference did not reach statistical significance.

Expression of the Sonic Hedgehog Embryonic Signalling Pathway Components in Matched Pre-Treatment and Relapsed Small Cell Lung Cancer Biopsies

Pauls Stradņš Clinical University Hospital

Faculty of Physics, Mathematics, and Optometry

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Cancer stem cells may be responsible for tumour regrowth and acquisition of resistance in small cell lung cancer (SCLC). The Hedgehog pathway regulates...

Expression of the Sonic Hedgehog Embryonic Signalling Pathway Components in Matched Pre-Treatment and Relapsed Small Cell Lung Cancer Biopsies

Data publikacji: 15 lis 2021

Zakres stron: 335 - 342

Otrzymano: 09 lut 2021

Przyjęty: 27 maj 2021

DOI: https://doi.org/10.2478/prolas-2021-0049

Słowa kluczowe
relapsed SCLC, cancer stem cells, Sonic Hedgehog pathway, gene expression, matched biopsies

© 2021 Viktors Kozirovskis et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Expression of the Sonic Hedgehog Embryonic Signalling Pathway Components in Matched Pre-Treatment and Relapsed Small Cell Lung Cancer Biopsies

Data publikacji: 15 lis 2021

Zakres stron: 335 - 342

Otrzymano: 09 lut 2021

Przyjęty: 27 maj 2021

DOI: https://doi.org/10.2478/prolas-2021-0049

Słowa kluczowerelapsed SCLC, cancer stem cells, Sonic Hedgehog pathway, gene expression, matched biopsies

© 2021 Viktors Kozirovskis et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Słowa kluczowe
relapsed SCLC, cancer stem cells, Sonic Hedgehog pathway, gene expression, matched biopsies