bims-exocan 2024-10-27 papers

Issue of 2024–10–27
five papers selected by
Muhammad Rizwan, COMSATS University

Medicine (Baltimore). 2024 Oct 18. 103(42): e40082

Exosomal miRNA as biomarker in cancer diagnosis and prognosis: A review.

Mingliao Zhu, Yuan Gao, Kaijun Zhu, Ying Yuan, Haoyang Bai, Liwei Meng.

Exosomes, which are extracellular vesicles with a diameter ranging from 40 to 160 nm, are abundantly present in various body fluids. Exosomal microRNA (ex-miR), due to its exceptional sensitivity and specificity, has garnered significant attention. Notably, ex-miR is consistently detected in almost all bodily fluids, highlighting its potential as a reliable biomarker. This attribute of ex-miR has piqued considerable interest in its application as a diagnostic tool for the early detection, continuous monitoring, and prognosis evaluation of cancer. Given the critical role of exosomes and their cargo in cancer biology, this review explores the intricate processes of exosome biogenesis and uptake, their multifaceted roles in cancer development and progression, and the potential of ex-miRs as biomarkers for tumor diagnosis and prognosis.

DOI: https://doi.org/10.1097/MD.0000000000040082

Front Pharmacol. 2024 ;15 1466424

Insights about exosomal circular RNAs as novel biomarkers and therapeutic targets for hepatocellular carcinoma.

Haiyan Zhang, Shanshan Pei, Jiaxuan Li, Jiajie Zhu, Hongyu Li, Guangshang Wu, Ruiqi Weng, Ruyi Chen, Zhongbiao Fang, Jingbo Sun, Keda Chen.

One of the most prevalent pathological types of Primary Liver Cancer (PLC) is the Hepatocellular Carcinoma (HCC) poses a global health issue. The high recurrence and metastasis rate of HCC, coupled with a low 5-year survival rate, result in a bleak prognosis. Exosomes, small extracellular vesicles released by various cells, contain diverse non-coding RNA molecules, including circular RNAs (circRNAs), which play a significant role in intercellular communication and can impact HCC progression. Studies have revealed the potential clinical applications of exosomal circRNAs as biomarkers and therapeutic targets for HCC. These circRNAs can be transferred via exosomes to nearby non-cancerous cells, thereby regulating HCC progression and influencing malignant phenotypes, such as cell proliferation, invasion, metastasis, and drug resistance. This review provides a comprehensive overview of the identified exosomal circRNAs, highlighting their potential as non-invasive biomarkers for HCC, and suggesting new perspectives for HCC diagnosis and treatment. The circRNA from exosomal organelles promotes metastasis and immune scape because of their unique chirality which is different from the Biomolecular Homochirality.

Keywords: biomarker; cancer therapy; circRNA; exosomes; hepatocellular carcinoma

DOI: https://doi.org/10.3389/fphar.2024.1466424

Cancer Med. 2024 Oct;13(20): e70265

Exosomal miR-199a-3p Secreted From Cancer-Associated Adipocytes Promotes Pancreatic Cancer Progression.

Kazuyoshi Noda, Yasushi Sato, Yasuyuki Okada, Kensei Nishida, Yutaka Kawano, Toshihito Tanahashi, Masahiro Bando, Koichi Okamoto, Masanori Takehara, Masahiro Sogabe, Hiroshi Miyamoto, Kei Daizumoto, Hiroomi Kanayama, Tetsuji Takayama.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer. Recent studies indicated that cancer-associated adipocytes (CAAs) play crucial roles in tumor progression; however, the precise mechanism remains unknown. Here, we analyzed specific exosomal microRNAs (miRNA) signatures derived from pancreatic CAAs to investigate their role in cancer progression.
METHODS: CAAs were generated by co-culturing human adipocytes with human pancreatic cancer cells, and exosomes were isolated from the CAA-conditioned medium (CAA-CM). Small RNA-seq analysis was used to identify differentially expressed miRNAs in these exosomes. The effects of miRNAs on cell proliferation, migration/invasion, and drug sensitivity were examined. Luciferase reporter assays, real-time polymerase chain reaction, and western blotting were performed to investigate the molecular mechanisms of the miRNAs. The clinical relevance of the miRNAs was investigated using publicly available data and our cohort of patients with PDAC.
RESULTS: miR-199a-3p expression was significantly increased in CAA-CM-derived exosomes. CAA-derived exosomes transferred miR-199a-3p to pancreatic cancer cells. Transfection with miR-199a-3p increased the proliferation, invasion, migration, and drug resistance of pancreatic cancer cells by downregulating SOCS7, increasing STAT3 phosphorylation, and upregulating SAA1 expression. High tissue miR-199a-3p expression is correlated with poor prognosis in patients with PDAC. Liquid biopsies revealed that exosomal miR-199a-3p could accurately differentiate patients with PDAC from healthy controls. Multivariate survival analysis indicated that miR-199a is an independent prognostic factor for PDAC.
CONCLUSION: miR-199a-3p in CAA-derived exosomes contributes to the malignant transformation of pancreatic cancer via the SOCS7/STAT3/SAA1 pathway, suggesting its potential as a biomarker and therapeutic target for PDAC.

Keywords: biomarker; cancer‐associated adipocytes; miR‐199a‐3p; pancreatic ductal adenocarcinoma

DOI: https://doi.org/10.1002/cam4.70265

Front Genet. 2024 ;15 1425591

Identification of plasma exosomal lncRNA as a biomarker for early diagnosis of gastric cancer.

Ye Wei, Xuming Hu, Shuai Yuan, Yue Zhao, Chunhui Zhu, Mingzhou Guo, Hengmi Cui.

Background: There were about 1,090,000 gastric cancer (GC) cases in 2020 in China. The incidence and mortality rates ranked the fifth and third among all kinds of cancers in China. Early diagnosis plays an important role in the treatment and prognosis of gastric cancer. In recent years, noninvasive diagnosis, especially plasma exosome lncRNAs, has become a promissing biomarkers with high specificity and sensitivity for early diagnosis of cancers.
Methods: In this study, plasma exosomes of patients with early gastric cancer were extracted efficiently by affinity membrane separation technology, including affinity adsorption, elution, affinity membrane regeneration and other steps. After identified by electron microscopy observation, particle size analysis and Western blot verification, the lncRNAs in the exosomes were extracted and were analysized by high-throughput RNA sequencing (RNA-Seq). The differentially expressed lncRNAs were verified by RT-qPCR in 93 patients with early gastric cancer and 49 normal controls.
Results: Electron microscopy, particle size analysis and Western blot showed that exosomes were successfully isolated from plasma. RNA-Seq results show that 76 lncRNAs were upregulated and 260 lncRNAs were downregulated in plasma exosomes of early gastric cancer patients compared with normal controls. RT-qPCR analysis indicated that a total of 6 lncRNAs were significantly and differentially expressed in gastric cancer patients compared to normal controls, with 2 (lncmstrg. 1319590, Lncmstrg. 2312697) highly expressed and 4 lowly expressed (lncmstr-g.1004024.1, lncmstrg. 2441832.8, lncmstrg. 315376.1, lncmstrg.907985.2,) (p < 0.05). The survival curve analysis indicated that lncmstrg.2441832.8 and lncmstrg.2312697 had higher sensitivity and specificity for the diagnosis of gastric cancer, respectively and AUC curve areas were 0.6211 and 0.631, p < 0.05, respectively, which were greater than the traditional clinical detection indexes CEA (0.61) and AFP (0.57). When combined lncmstrg.2441832.8 and lncmstrg.2312697 in gastric cancer diagnosis, AUC curve area reached 0.73, which was greater than CA199 (0.71).
Conclusion: Lncmstrg.2441832.8 and lncmstrg.2312697 may be a potential and promissing biomarkers for early diagnosis of gastric cancer.

Keywords: diagnosis biomarker; early diagonsis; exosome; gastric cancer; lncRNA

DOI: https://doi.org/10.3389/fgene.2024.1425591

Clin Chim Acta. 2024 Oct 20. pii: S0009-8981(24)02264-2. [Epub ahead of print] 120011

Ovarian cancer extracellular vesicle biomarkers.

Zeinab Jamali, Masoumeh Razipour, Mahsa Zargar, Hojat Ghasemnejad Berenji, Seyed Mohammad Akrami.

Ovarian cancer (OC) remains a significant women's health concern due to its high mortality rate and the challenges posed by late detection. Exploring novel biomarkers could lead to earlier, more specific diagnoses and improved survival rates for OC patients. This review focuses on biomarkers associated with extracellular vesicles (EVs) found in various proximal fluids, including urine, ascites, utero-tubal lavage fluid of OC patients. We highlight these proximal fluids as rich sources of potential biomarkers. The review explains the roles of EV biomarkers in ovarian cancer progression and discusses EV-related proteins and miRNAs as potential diagnostic or prognostic indicators and therapeutic targets. Finally, we highlighted the limitations of examining proximal fluids as sources of biomarkers and encourage researchers to proactively pursue innovative solutions to overcome these challenges.

Keywords: Biomarker; Diagnosis; Extracellular vesicle; Ovarian cancer

DOI: https://doi.org/10.1016/j.cca.2024.120011