X or Y Cancer: An Extensive Analysis of Sex Differences in Lung Adenocarcinoma
<b>Background:</b> Cellular metabolism is a tightly controlled process during which cell growth and survival are maintained. Lung cancer is a disease with clear sex differences, where female patients have better survival rates than males. Evidence of sex differences is demonstrated in ca...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/30/2/107 |
| _version_ | 1797621557513682944 |
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| author | Raneem Yaseen Hammouz Magdalena Orzechowska Dorota Anusewicz Andrzej K. Bednarek |
| author_facet | Raneem Yaseen Hammouz Magdalena Orzechowska Dorota Anusewicz Andrzej K. Bednarek |
| author_sort | Raneem Yaseen Hammouz |
| collection | DOAJ |
| description | <b>Background:</b> Cellular metabolism is a tightly controlled process during which cell growth and survival are maintained. Lung cancer is a disease with clear sex differences, where female patients have better survival rates than males. Evidence of sex differences is demonstrated in cancer risk, prognosis and response to different therapies, yet a sex-specific approach to cancer studies is not widely considered. These different tumour characteristics attributed to sex that impact disease outcome, including constitutional genetic and somatic molecular differences, make it essential to assess viral and hormonal influences. <b>Methods:</b> In silico analysis of lung adenocarcinoma (LUAD) TCGA data, including K-means clustering algorithm, dimensional reduction with principal component analysis and differential expression analysis using EdgeR (<i>p</i> < 0.05), were used to explore some robust sex differences in LUAD that exist in core signalling pathways and metabolic processes between males and females. The correlation of differentially expressed genes (DEGs) expression with immune abundance in the LUAD cohort was analysed on TIMER2.0 and adjusted by tumour purity utilising Cox proportional hazard. Multiple factorial analysis heatmap visualisation was used to examine endogenous steroid hormonal effects on LUAD patients with different smoking status and age groups. <b>Results:</b> We found 161 DEGs showing key differences in regulation of immune system and cellular homeostasis, key elements of divergent cancer progression, between the two sexes. We also found male and female LUAD patients to favour different metabolic intermediates for energy production to support tumourigenesis. Additionally, high levels of Tregs accompanied by DEGs correlated with better LUAD prognosis, and circulating hormonal transcriptional targets affect proliferation and progression in males and females differently. Finally, we examined the role of oestrogen protection in men and pre-/postmenopausal women. <b>Conclusions:</b> Further studies should focus on sex-specific changes and investigate sex-specific gene regulatory networks of these DEGs. Several lifestyle factors, including tobacco smoking and diet, differ between males and females. These factors might affect metabolic pathways and can influence the activity of epigenetic regulators, resulting in significant global epigenetic changes. |
| first_indexed | 2024-03-11T08:57:42Z |
| format | Article |
| id | doaj.art-2e94ad0a62094ac589842c7b1444eea6 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-11T08:57:42Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-2e94ad0a62094ac589842c7b1444eea62023-11-16T19:57:23ZengMDPI AGCurrent Oncology1198-00521718-77292023-01-013021395141510.3390/curroncol30020107X or Y Cancer: An Extensive Analysis of Sex Differences in Lung AdenocarcinomaRaneem Yaseen Hammouz0Magdalena Orzechowska1Dorota Anusewicz2Andrzej K. Bednarek3Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752 Lodz, PolandDepartment of Molecular Carcinogenesis, Medical University of Lodz, 90-752 Lodz, PolandDepartment of Molecular Carcinogenesis, Medical University of Lodz, 90-752 Lodz, PolandDepartment of Molecular Carcinogenesis, Medical University of Lodz, 90-752 Lodz, Poland<b>Background:</b> Cellular metabolism is a tightly controlled process during which cell growth and survival are maintained. Lung cancer is a disease with clear sex differences, where female patients have better survival rates than males. Evidence of sex differences is demonstrated in cancer risk, prognosis and response to different therapies, yet a sex-specific approach to cancer studies is not widely considered. These different tumour characteristics attributed to sex that impact disease outcome, including constitutional genetic and somatic molecular differences, make it essential to assess viral and hormonal influences. <b>Methods:</b> In silico analysis of lung adenocarcinoma (LUAD) TCGA data, including K-means clustering algorithm, dimensional reduction with principal component analysis and differential expression analysis using EdgeR (<i>p</i> < 0.05), were used to explore some robust sex differences in LUAD that exist in core signalling pathways and metabolic processes between males and females. The correlation of differentially expressed genes (DEGs) expression with immune abundance in the LUAD cohort was analysed on TIMER2.0 and adjusted by tumour purity utilising Cox proportional hazard. Multiple factorial analysis heatmap visualisation was used to examine endogenous steroid hormonal effects on LUAD patients with different smoking status and age groups. <b>Results:</b> We found 161 DEGs showing key differences in regulation of immune system and cellular homeostasis, key elements of divergent cancer progression, between the two sexes. We also found male and female LUAD patients to favour different metabolic intermediates for energy production to support tumourigenesis. Additionally, high levels of Tregs accompanied by DEGs correlated with better LUAD prognosis, and circulating hormonal transcriptional targets affect proliferation and progression in males and females differently. Finally, we examined the role of oestrogen protection in men and pre-/postmenopausal women. <b>Conclusions:</b> Further studies should focus on sex-specific changes and investigate sex-specific gene regulatory networks of these DEGs. Several lifestyle factors, including tobacco smoking and diet, differ between males and females. These factors might affect metabolic pathways and can influence the activity of epigenetic regulators, resulting in significant global epigenetic changes.https://www.mdpi.com/1718-7729/30/2/107adenocarcinomasexmetabolismhormonesmenopauseimmune |
| spellingShingle | Raneem Yaseen Hammouz Magdalena Orzechowska Dorota Anusewicz Andrzej K. Bednarek X or Y Cancer: An Extensive Analysis of Sex Differences in Lung Adenocarcinoma Current Oncology adenocarcinoma sex metabolism hormones menopause immune |
| title | X or Y Cancer: An Extensive Analysis of Sex Differences in Lung Adenocarcinoma |
| title_full | X or Y Cancer: An Extensive Analysis of Sex Differences in Lung Adenocarcinoma |
| title_fullStr | X or Y Cancer: An Extensive Analysis of Sex Differences in Lung Adenocarcinoma |
| title_full_unstemmed | X or Y Cancer: An Extensive Analysis of Sex Differences in Lung Adenocarcinoma |
| title_short | X or Y Cancer: An Extensive Analysis of Sex Differences in Lung Adenocarcinoma |
| title_sort | x or y cancer an extensive analysis of sex differences in lung adenocarcinoma |
| topic | adenocarcinoma sex metabolism hormones menopause immune |
| url | https://www.mdpi.com/1718-7729/30/2/107 |
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