Research on the effect of LAMP1 in the development and progression of ccRCC and its potential mechanism with LC3C-mediated autophagy

BackgroundLysomembrane-associated protein 1 (LAMP1), known to exhibit differential expression in various tumor types and play a crucial role in the development of tumors. Clear cell Renal Cell Carcinoma (ccRCC) is still the most common pathological type of renal carcinoma with poor prognosis. Howeve...

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Main Authors: Xiongbao Wang, Liang Fang, Lixiang Xiao, Guangxin Zhong, Minghao Han, Bingshen Wang, Juchao Ren, Yuanwei Zang
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1494005/full
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author Xiongbao Wang
Xiongbao Wang
Xiongbao Wang
Liang Fang
Liang Fang
Lixiang Xiao
Guangxin Zhong
Minghao Han
Bingshen Wang
Juchao Ren
Yuanwei Zang
Yuanwei Zang
author_facet Xiongbao Wang
Xiongbao Wang
Xiongbao Wang
Liang Fang
Liang Fang
Lixiang Xiao
Guangxin Zhong
Minghao Han
Bingshen Wang
Juchao Ren
Yuanwei Zang
Yuanwei Zang
author_sort Xiongbao Wang
collection DOAJ
description BackgroundLysomembrane-associated protein 1 (LAMP1), known to exhibit differential expression in various tumor types and play a crucial role in the development of tumors. Clear cell Renal Cell Carcinoma (ccRCC) is still the most common pathological type of renal carcinoma with poor prognosis. However, the expression of LAMP1 and its underlying molecular mechanism with ccRCC remain elusive.MethodsFirstly, the expression of LAMP1 in ccRCC and its clinical significance were analyzed using various databases. Next, Weston Blot was performed to detect the expression of LAMP1 protein in cancer tissues and adjacent tissues from 60 pairs of clinical ccRCC patients. The correlation between LAMP1 expression and different clinical indicators as well as the relationship with patient prognosis was analyzed. Furthermore, molecular cell biology experiments were conducted to validate the effects of LAMP1 gene expression on cell proliferation, invasion and migration. Additionally, we investigated the impact of VHL, a key gene in renal cancer, and LC3C, an autophagy-related gene, on LAMP1 expression through molecular biology experiments to elucidate the potential underlying mechanism.ResultsBioinformatics analysis revealed significant underexpression of LAMP1 in ccRCC (P<0.001), which correlated with poorer prognosis. In multivariate survival analysis, LAMP1 emerged as an independent prognostic marker for overall survival(OS)(P<0.05). Analysis of cancer and paracancer tissue samples from ccRCC patients demonstrated significantly lower levels of LAMP1 in tumors compared to paracancerous tissues (P<0.001), confirming its prognostic impact. Cell functionality experiment revealed that elevated LAMP1 inhibited cell proliferation, migration, and invasion. LAMP1 expression remained unchanged during autophagy modulation but decreased with LC3C knockdown and vice versa. Notably, VHL(+) cells expressed less LAMP1 than VHL(-) cells.ConclusionsThese findings indicate that low expression levels of LAMP1 is associated with poor prognosis in ccRCC. Therefore, LAMP1 emerges as a novel biomarker associated with the diagnosis and prognosis of renal cancer. Furthermore, we have also described the potential mechanism of action of LAMP1 in renal cancer. LAMP1 is a promising target for the treatment of ccRCC.
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spelling doaj-art-3e52c4cd2e724f48a655d6c873536efc2025-08-20T01:54:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14940051494005Research on the effect of LAMP1 in the development and progression of ccRCC and its potential mechanism with LC3C-mediated autophagyXiongbao Wang0Xiongbao Wang1Xiongbao Wang2Liang Fang3Liang Fang4Lixiang Xiao5Guangxin Zhong6Minghao Han7Bingshen Wang8Juchao Ren9Yuanwei Zang10Yuanwei Zang11Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaLaboratory of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaLaboratory of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaCheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Urology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, ChinaCheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaCheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaLaboratory of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaBackgroundLysomembrane-associated protein 1 (LAMP1), known to exhibit differential expression in various tumor types and play a crucial role in the development of tumors. Clear cell Renal Cell Carcinoma (ccRCC) is still the most common pathological type of renal carcinoma with poor prognosis. However, the expression of LAMP1 and its underlying molecular mechanism with ccRCC remain elusive.MethodsFirstly, the expression of LAMP1 in ccRCC and its clinical significance were analyzed using various databases. Next, Weston Blot was performed to detect the expression of LAMP1 protein in cancer tissues and adjacent tissues from 60 pairs of clinical ccRCC patients. The correlation between LAMP1 expression and different clinical indicators as well as the relationship with patient prognosis was analyzed. Furthermore, molecular cell biology experiments were conducted to validate the effects of LAMP1 gene expression on cell proliferation, invasion and migration. Additionally, we investigated the impact of VHL, a key gene in renal cancer, and LC3C, an autophagy-related gene, on LAMP1 expression through molecular biology experiments to elucidate the potential underlying mechanism.ResultsBioinformatics analysis revealed significant underexpression of LAMP1 in ccRCC (P<0.001), which correlated with poorer prognosis. In multivariate survival analysis, LAMP1 emerged as an independent prognostic marker for overall survival(OS)(P<0.05). Analysis of cancer and paracancer tissue samples from ccRCC patients demonstrated significantly lower levels of LAMP1 in tumors compared to paracancerous tissues (P<0.001), confirming its prognostic impact. Cell functionality experiment revealed that elevated LAMP1 inhibited cell proliferation, migration, and invasion. LAMP1 expression remained unchanged during autophagy modulation but decreased with LC3C knockdown and vice versa. Notably, VHL(+) cells expressed less LAMP1 than VHL(-) cells.ConclusionsThese findings indicate that low expression levels of LAMP1 is associated with poor prognosis in ccRCC. Therefore, LAMP1 emerges as a novel biomarker associated with the diagnosis and prognosis of renal cancer. Furthermore, we have also described the potential mechanism of action of LAMP1 in renal cancer. LAMP1 is a promising target for the treatment of ccRCC.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1494005/fullLAMP1renal cancerbiomarkersbioinformaticsprognosis
spellingShingle Xiongbao Wang
Xiongbao Wang
Xiongbao Wang
Liang Fang
Liang Fang
Lixiang Xiao
Guangxin Zhong
Minghao Han
Bingshen Wang
Juchao Ren
Yuanwei Zang
Yuanwei Zang
Research on the effect of LAMP1 in the development and progression of ccRCC and its potential mechanism with LC3C-mediated autophagy
Frontiers in Immunology
LAMP1
renal cancer
biomarkers
bioinformatics
prognosis
title Research on the effect of LAMP1 in the development and progression of ccRCC and its potential mechanism with LC3C-mediated autophagy
title_full Research on the effect of LAMP1 in the development and progression of ccRCC and its potential mechanism with LC3C-mediated autophagy
title_fullStr Research on the effect of LAMP1 in the development and progression of ccRCC and its potential mechanism with LC3C-mediated autophagy
title_full_unstemmed Research on the effect of LAMP1 in the development and progression of ccRCC and its potential mechanism with LC3C-mediated autophagy
title_short Research on the effect of LAMP1 in the development and progression of ccRCC and its potential mechanism with LC3C-mediated autophagy
title_sort research on the effect of lamp1 in the development and progression of ccrcc and its potential mechanism with lc3c mediated autophagy
topic LAMP1
renal cancer
biomarkers
bioinformatics
prognosis
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1494005/full
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