Prognostic Significance of LC3B and p62/SQSTM1 Expression in Gastric Adenocarcinoma

Kim, Ju Seok; Bae, Go Eun; Kim, Kyung‐Hee; S, Lee; Chung, Chaeuk; Lee, Da Hye; Lee, Tae Hee; Kwon, In Sun; Yeo, Min‐Kyung

doi:10.21873/anticanres.13886

Cited by 32 publications

(25 citation statements)

References 23 publications

(26 reference statements)

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“…Clinicopathological studies of liver tumors have demonstrated that LC3 expression may serve as an important prognostic factor for hepatocellular carcinoma, particularly for those patients undergoing surgical resection (28). The association between increased LC3 expression and a poor prognosis in gastric cancer has been extensively studied (29)(30)(31). All these studies have indicated that LC3 may be used as an independent prognostic indicator for patients with gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

LACTB and LC3 could serve as potential biomarkers of gastric cancer to neoadjuvant chemotherapy with oxaliplatin plus S‑1

et al. 2021

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The present study investigated and evaluated the correlation between the expression of LACTB and LC3 and the clinical outcomes of patients with advanced gastric cancer treated with oxaliplatin plus S-1 neoadjuvant chemotherapy (NACT). A total of 51 patients with advanced gastric cancer underwent NACT treatment between June 2015 and June 2017. Pathomorphological changes in gastric cancer were analyzed by H&E staining. The expression level and subcellular localization of LACTB and LC3 in paraffin-embedded biopsies were detected by immunohistochemistry and immunofluorescence. The mRNA and protein expression of LACTB were investigated by reverse transcription quantitative polymerase chain reaction and Western blotting, respectively. Statistical analysis was performed to determine the association between the expression of LACTB and LC3 and clinical chemotherapy efficacy of NACT for gastric cancer. Among the 51 patients, 3 (5.88%), 27 (52.94%), 13 (25.49%) and 8 (15.69%) displayed complete remission, partial remission, stable disease and progressive disease, respectively. The rate of decreased LACTB expression was 68.6%, while the rate of increased LC3 expression was 60.8%. Furthermore, there was a significant negative correlation between the expression of LACTB and that of LC3 following NACT (P<0.001). High expression of LC3 (P<0.01) and low expression of LACTB (P<0.01) were associated with a poor response of patients with advanced gastric cancer to NACT. In conclusion, the expression of LACTB and LC3 may serve as a promising novel biomarker for determining the prognosis of patients with advanced gastric cancer receiving NACT, while its potential clinical significance requires further elucidation.

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Section: Discussionmentioning

confidence: 99%

LACTB and LC3 could serve as potential biomarkers of gastric cancer to neoadjuvant chemotherapy with oxaliplatin plus S‑1

et al. 2021

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“…Could be the underlying mechanism of XPO1 inhibitor activity in gastric cancer. This gives and opportunity to combine XPO1 inhibitor with various cytotoxic compounds that otherwise are not effective in generating an effective therapeutic response due to autophagy [186]. Sequestration of p62 into the nucleus may also cause sensitization to immunotherapeutic agents such as PDL1 inhibitors [186,187].…”

Section: P62mentioning

confidence: 99%

Gastric cancer: a comprehensive review of current and future treatment strategies

Sexton

Hallak

Diab

et al. 2020

Cancer Metastasis Rev

415

251

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Gastric cancer remains a major unmet clinical problem with over 1 million new cases worldwide. It is the fourth most commonly occurring cancer in men and the seventh most commonly occurring cancer in women. A major fraction of gastric cancer has been linked to variety of pathogenic infections including but not limited to Helicobacter pylori (H. pylori) or Epstein Barr virus (EBV). Strategies are being pursued to prevent gastric cancer development such as H. pylori eradication, which has helped to prevent significant proportion of gastric cancer. Today, treatments have helped to manage this disease and the 5-year survival for stage IA and IB tumors treated with surgery are between 60 and 80%. However, patients with stage III tumors undergoing surgery have a dismal 5-year survival rate between 18 and 50% depending on the dataset. These figures indicate the need for more effective molecularly driven treatment strategies. This review discusses the molecular profile of gastric tumors, the success, and challenges with available therapeutic targets along with newer biomarkers and emerging targets.

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“…P62 is a ubiquitin-binding protein that is closely associated with the ubiquitination of proteins. P62 is involved in the regulation of a variety of cellular signal transduction pathways and autophagy ( 78 ). In autophagy, p62 binds to ubiquitin, forms a complex with LC3-II located on the autophagic membrane, and is degraded in the autophagic lysosome.…”

Section: Signaling Pathways In Autophagy and Tumorsmentioning

confidence: 99%

Autophagy-related signaling pathways are involved in cancer (Review)

Chen

Gao

2021

Exp Ther Med

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Autophagy is a self-digestion process in cells that can maintain energy homeostasis under normal circumstances. However, misfolded proteins, damaged mitochondria and other unwanted components in cells can be decomposed and reused via autophagy in some specific cases (including hypoxic stress, low energy states or nutrient deprivation). Therefore, autophagy serves a positive role in cell survival and growth. However, excessive autophagy may lead to apoptosis. Furthermore, abnormal autophagy may lead to carcinogenesis and promote tumorigenesis in normal cells. In tumor cells, autophagy may provide the energy required for excessive proliferation, promote the growth of cancer cells, and evade apoptosis caused by certain treatments, including radiotherapy and chemotherapy, resulting in increased treatment resistance and drug resistance. On the other hand, autophagy leads to an insufficient nutrient supply in cancer cells and the destruction of energy homeostasis, thereby inducing cancer cell apoptosis. Therefore, understanding the mechanism of the double-edged sword of autophagy is crucial for the treatment of cancer. The present review summarizes the signaling pathways and key factors involved in autophagy and cancer to provide possible strategies for treating tumors.

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Prognostic Significance of LC3B and p62/SQSTM1 Expression in Gastric Adenocarcinoma

Cited by 32 publications

References 23 publications

LACTB and LC3 could serve as potential biomarkers of gastric cancer to neoadjuvant chemotherapy with oxaliplatin plus S‑1

LACTB and LC3 could serve as potential biomarkers of gastric cancer to neoadjuvant chemotherapy with oxaliplatin plus S‑1

Gastric cancer: a comprehensive review of current and future treatment strategies

Autophagy-related signaling pathways are involved in cancer (Review)

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