Dataset Information

Overexpressed p-S6 associates with lymph node metastasis and predicts poor prognosis in non-small cell lung cancer.

ABSTRACT:

Background

Ribosomal protein S6 (S6), a downstream effect media of the AKT/mTOR pathway, not only is a part of 40S small subunit of eukaryotic ribosome, but also involves in protein synthesis and cell proliferation during cancer development.

Methods

In present study, we explore the association between phosphorylated S6 (p-S6) protein expression and clinicopathological features as well as prognostic implications in NSCLC. P-S6 was detected in tissue microarrays (TMAs) containing 350 NSCLC, 53 non-cancerous lung tissues (Non-CLT), and 88 cases of matched metastatic lymph node lesions via immunohistochemistry (IHC). Transwell assays and wound healing assay were used to assess the effects of p-S6 inhibition on NSCLC cell metastasis.

Results

The p-S6 expression in NSCLC was more evident than that in Non-CLT (p < 0.05). Compared to NSCLC patients who have no lymph node metastasis (LNM), those with LNM had higher p-S6 expression (p = 0.001). Regardless of lung squamous cell carcinoma (SCC) or adenocarcinoma (ADC), p-S6 was increased obviously in metastatic lymph nodes compared with matched primary cancers (p = 0.001, p = 0.022, respectively). Inhibition of p-S6 decreased the metastasis ability of NSCLC cells. In addition, p-S6 was an independent predicted marker for LNM in patients with NSCLC (p < 0.001). According to survival analysis, patients with highly expressed p-S6 had a lower survival rate compared with that with lower expression (p = 0.013). P-S6 is an unfavorable independent prognostic factor for NSCLC patients (p = 0.011).

Conclusion

Increased expression of p-S6 is not only a novel predictive biomarker of LNM but also poor prognosis in NSCLC.

SUBMITTER: Tang Y

PROVIDER: S-EPMC9123697 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Overexpressed p-S6 associates with lymph node metastasis and predicts poor prognosis in non-small cell lung cancer.

Tang Yaoxiang Y Luo Jiadi J Zhou Ying Y Zang Hongjing H Yang Yang Y Liu Sile S Zheng Hongmei H Ma Jian J Fan Songqing S Wen Qiuyuan Q

BMC cancer 20220520 1

<h4>Background</h4>Ribosomal protein S6 (S6), a downstream effect media of the AKT/mTOR pathway, not only is a part of 40S small subunit of eukaryotic ribosome, but also involves in protein synthesis and cell proliferation during cancer development.<h4>Methods</h4>In present study, we explore the association between phosphorylated S6 (p-S6) protein expression and clinicopathological features as well as prognostic implications in NSCLC. P-S6 was detected in tissue microarrays (TMAs) containing 35 ...[more]

PMID: 35596155

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Project description:PurposeMolecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methodsThis study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan-Meier analysis with a log-rank test was used for the survival analysis.ResultsLAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.ConclusionThese findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients.

Project description:Lung cancer is a common malignancy that is difficult to treat and has a high risk of mortality. Although gastrointestinal lymph node metastasis has long been known to exert major impact on the prognosis of lung cancer, the mechanism of its occurrence and potential biological markers remain elusive. Therefore, the present study retrospectively analyzed data from 132 patients with non-small cell lung cancer (NSCLC) combined with lymph node metastasis between February 2010 and April 2019 from the First Affiliated Hospital of Soochow University (Suzhou, China) and Sichuan Cancer Hospital (Chengdu, China). Overall survival was assessed using Kaplan-Meier analysis and Cox logistic regression model. In addition, a prediction model was constructed based on immune indicators such as complement C3b and C4d (measured by ELISA), before the accuracy of this model was validated using calibration curves for 5-year OS. Among the 132 included patients, a total of 92 (70.0%) succumbed to the disease within 5 years. Multifactorial analysis revealed that complement C3b deficiency increased the risk of mortality by nearly two-fold [hazard ratio (HR)=2.23; 95% CI=1.20-4.14; P=0.017], whilst complement C4d deficiency similarly increased the risk of mortality by two-fold (HR=2.14; 95% CI=1.14-4.00; P=0.012). The variables were subsequently screened using Cox model to construct a prediction model based on complement C3b and C4d levels before a Nomogram plotted. By internal validation for the 132 patients, the Nomogram accurately estimated the risk of mortality, with a corrected C-index of 0.810. External validation of the model in another 50 patients from Sichuan Cancer Hospital revealed an accuracy of 77.0%. Overall, this mortality risk prediction model constructed based on complement levels showed accuracy in assessing the prognosis of patients with metastatic NSCLC. Therefore, complement C3b and C4d have potential for use as biomarkers to predict the risk of mortality in such patients.

Dataset Information

Overexpressed p-S6 associates with lymph node metastasis and predicts poor prognosis in non-small cell lung cancer.

Background

Methods

Results

Conclusion

Publications

Overexpressed p-S6 associates with lymph node metastasis and predicts poor prognosis in non-small cell lung cancer.

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