LETM1 is a potential cancer stem-like cell marker and predicts poor prognosis in colorectal adenocarcinoma

Piao, Lihua; Feng, Ying; Yang, Zheng; Qi, Wenbo; Li, Haoyue; Han, Hengmin; Xuan, Yanhua

doi:10.1016/j.prp.2019.152437

Cited by 23 publications

(21 citation statements)

References 22 publications

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“…Recent studies have shown that high LETM1 expression is associated with poor prognosis and clinicopathological parameters of various human cancers. [20][21][22][23][24] In spite of the difference in organs and cancer types, our findings are highly consistent with previous studies in which LETM1 expression was significantly higher in PCa than in BPH tissue. Moreover, the level of LETM1 expression was significantly associated with advanced grade, pT, and clinical stages.…”

Section: Discussionsupporting

confidence: 91%

“…28 Our previous study showed that LETM1 may serve as a novel cancer stemness gene for the prognostic evaluation of CRA and ESCC. 20,24 In this study, stemness-related proteins were found to be co-upregulated with LETM1 in PCa cells. Furthermore, LETM1 knockdown significantly downregulated CD44, SOX2, and LSD1 expression and the clonogenic ability of PCa cells.…”

Section: Discussionmentioning

confidence: 51%

“…17 Recent studies have shown that LETM1 regulates tumorigenesis, tumor progression, and cancer stemness. 20,24 However, to our knowledge, this is the first study that investigated the relationship between LETM1 expression and cancer cell stemness and EMT-related proteins in PCa and clarified the significance of LETM1 expression in PCa tissues. Recent studies have shown that high LETM1 expression is associated with poor prognosis and clinicopathological parameters of various human cancers.…”

Section: Discussionmentioning

confidence: 94%

“…18,19 LETM1 is a biomarker associated with poor prognosis and tumor progression in patients with colorectal adenocarcinoma as well as breast, bladder, thyroid, and esophageal cancers. [20][21][22][23][24] However, the clinical significance of LETM1, its function in tumorigenesis, and its regulation in PCa are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

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<p>Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer</p>

Piao¹,

Li²,

Feng³

et al. 2020

CMAR

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The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial protein that has been associated with the occurrence and development of malignant tumors. Previous studies have shown that LETM1 expression is increased in several types of human cancer and is associated with a poor clinical outcome. However, the role of LETM1 in prostate cancer (PCa) has not yet been determined. In this study, we investigated the clinicopathological significance of LETM1 expression and its role in PCa progression. Methods: We assessed the expression of LETM1 and genes related to cancer stemness, epithelial-mesenchymal transition (EMT), cell cycle, and PI3K/Akt signaling in 133 paraffinembedded PCa tissue samples and cancer cells by using immunohistochemistry, immunofluorescence, and Western blotting. Results: LETM1 expression was significantly increased in PCa, and it was positively correlated with Gleason score, pathologic tumor (pT) stage, clinical stage, and high microvessel density. Survival analysis showed that patients with PCa with a high level of LETM1 expression exhibited a low overall survival. Cox regression analysis indicated that LETM1 is an independent poor prognostic PCa factor. Additionally, the expression of LETM1 was correlated with cancer cell stemness-associated genes, EMT-related genes, cell cycle regulatory genes, and PI3K/Akt signaling gene expression in PCa. Furthermore, knocking down LETM1 expression down-regulated the expression of stemness-related proteins, while inhibiting tumor spheroid formation, EMT-like changes, cell proliferation, migration, and invasion in PCa cells. Importantly, the PI3K inhibitor LY294002 strongly inhibited the expression of LETM1, pPI3K-p85, and pAkt (Thr308, Ser473) in PCa cells. Conclusion: These results indicate that LETM1 expression is associated with cancer cell stemness, promotes EMT-like changes and cell proliferation and is a potential prognostic biomarker for PCa.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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<p>Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer</p>

Piao¹,

Li²,

Feng³

et al. 2020

CMAR

Self Cite

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“…Cancer stem–like cells (CSCs) comprise a small fraction of malignant cells and are responsible for cancer proliferation because of their capacity for self‐renewal 23 . Previous studies have shown that high LETM1 level is closely related to cancer stemness proteins in CRC 21 . Similarly, in this study, IF assays demonstrated that LETM1 was co‐expressed with CSC markers (CD44 and CD133) in CRC tissues (Figure A).…”

Section: Resultssupporting

confidence: 69%

Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species–induced autophagy

Che

Yang

Liu

et al. 2020

J Cellular Molecular Medi

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Leucine zipper‐EF‐hand–containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein that is highly expressed in various cancers. Although LETM1 is known to be associated with poor prognosis in colorectal cancer (CRC), its roles in autophagic cell death in CRC have not been explored. In this study, we examined the mechanisms through which LETM1 mediates autophagy in CRC. Our results showed that LETM1 was highly expressed in CRC tissues and that down‐regulation of LETM1 inhibited cell proliferation and induced S‐phase arrest. LETM1 silencing also suppressed cancer stem cell–like properties and induced autophagy in CRC cells. Additionally, the autophagy inhibitor 3‐methyladenine reversed the inhibitory effects of LETM1 silencing on proliferation and stemness, whereas the autophagy activator rapamycin had the opposite effects. Mechanistically, suppression of LETM1 increased the levels of reactive oxygen species (ROS) and mitochondrial ROS by regulation of SOD2, which in turn activated AMP‐activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), initiated autophagy, and inhibited proliferation and stemness. Our findings suggest that silencing LETM1 induced autophagy in CRC cells by triggering ROS‐mediated AMPK/mTOR signalling, thus blocking CRC progression, which will enhance our understanding of the molecular mechanism of LETM1 in CRC.

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Employing machine learning and microscopy images of AIB1‐stained biopsy material to assess the 5‐year survival of patients with colorectal cancer

Theodosi

Ouzounis

Kostopoulos

et al. 2021

Microscopy Res & Technique

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Our purpose was to employ microscopy images of amplified in breast cancer 1 (AIB1)‐stained biopsy material of patients with colorectal cancer (CRC) to: (a) find statistically significant differences (SSDs) in the texture and color of the epithelial gland tissue, between 5‐year survivors and non‐survivors after the first diagnosis and (b) employ machine learning (ML) methods for predicting the CRC‐patient 5‐year survival. We collected biopsy material from 54 patients with diagnosed CRC from the archives of the University Hospital of Patras, Greece. Twenty‐six of the patients had survived 5 years after the first diagnosis. We selected regions of interest containing the epithelial gland at different microscope lens magnifications. We computed 69 textural and color features. Furthermore, we identified features with SSDs between the two groups of patients and we designed a supervised ML system for predicting the CRC‐patient 5‐year survival. Additionally, we employed the VGG16 pretrained convolution neural network to extract deep learning (DL) features, the support vector machines classifier, and the bootstrap cross‐validation method for boosting the accuracy of predicting 5‐year survival. Fourteen features sustained SSDs between the two groups of patients. The supervised ML system achieved 87% accuracy in predicting 5‐year survival. In comparison, the DL system, using images from all magnifications, gave 97% classification accuracy. Glandular texture in 5‐year non‐survivors appeared to be of lower contrast, coarseness, roughness, local pixel correlation, and lower AIB1 variation, all indicating loss of textural definition. The supervised ML system revealed useful information regarding features that discriminate between 5‐year survivors and non‐survivors while the DL system displayed superior accuracy by employing DL features.

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LETM1 is a potential cancer stem-like cell marker and predicts poor prognosis in colorectal adenocarcinoma

Cited by 23 publications

References 22 publications

<p>Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer</p>

<p>Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer</p>

Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species–induced autophagy

Employing machine learning and microscopy images of AIB1‐stained biopsy material to assess the 5‐year survival of patients with colorectal cancer

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