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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1494005
This article is part of the Research Topic Precision Medicine and Targeted Therapies in Gastrointestinal and Genitourinary Solid Tumors View all 3 articles

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

Provisionally accepted
Xiongbao Wang Xiongbao Wang 1,2Liang Fang Liang Fang 1Guangxin Zhong Guangxin Zhong 3Minghao Han Minghao Han 4Bingshen Wang Bingshen Wang 4Juchao Ren Juchao Ren 1*Yuanwei Zang Yuanwei Zang 1*
  • 1 Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
  • 2 Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
  • 3 Department of Urology, Beijing Tsinghua Changgeng Hospital, Tsinghua University, Beijing, China
  • 4 Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

The final, formatted version of the article will be published soon.

    Background: Lysomembrane-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. Methods：Firstly, 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. Results: Bioinformatics 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. Conclusions: These 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.

    Keywords: LAMP1, renal cancer, biomarkers, bioinformatics, prognosis

    Received: 10 Sep 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Wang, Fang, Zhong, Han, Wang, Ren and Zang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Juchao Ren, Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
    Yuanwei Zang, Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China

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