PD-1/PD-L1 based immunochemotherapy versus chemotherapy alone for advanced esophageal squamous cell carcinoma: A meta-analysis focus on PD-L1 expression level.

BACKGROUND: Immunochemotherapy has become a new treatment for advanced esophageal squamous cell carcinoma (ESCC). AIMS: We aimed to study the clinical efficacy and toxicity of immunochemotherapy based on PD-1/PD-L1 compared with chemotherapy alone in the treatment of advanced ESCC, focusing on analyzing the influence of PD-L1 expression level. METHODS AND RESULTS: Five randomized controlled trials comparing PD-1/PD-L1 based immunochemotherapy with chemotherapy alone for advanced ESCC were included. We extracted efficacy data (objective response rate [ORR], disease control rate [DCR], overall survival [OS] rate, progression-free survival [PFS] rate) and safety data (treatment-related adverse events, treatment-related mortality) and performed meta-analyses. Compared with chemotherapy alone, the ORR and DCR of immunochemotherapy increased by 2.05 times and 1.54 times, respectively. Overall, patients receiving immunochemotherapy had a significant long-term survival advantage (OS: hazard ratio [HR] = 0.68, 95% confidence intervals [CI] 0.61-0.75; PFS: HR = 0.62, 95% CI 0.55, 0.70, respectively). Even with PD-L1 tumor proportion score <1%, immunochemotherapy also showed a significant survival advantage (OS: HR = 0.65, 95% CI 0.46-0.93; PFS: HR = 0.56, 95% CI 0.46-0.69, respectively). However, for PD-L1 combined positive score (CPS) < 1, the survival advantage of immunochemotherapy was not significant (OS: HR = 0.89, 95% CI 0.42-1.90; PFS: HR = 0.71, 95% CI 0.47-1.08, respectively). The toxicity of immunochemotherapy was higher than that of chemotherapy alone, but there was no statistical difference in treatment-related mortality (odds ratio = 1.11, 95% CI 0.67-1.83). CONCLUSION: In this study, treatment-related mortality was similar between immunochemotherapy and chemotherapy. PD-1/PD-L1 based immunochemotherapy significantly could improve survival outcomes in patients with advanced ESCC. For patients with CPS <1, the survival advantage of immunochemotherapy was not significant compared with chemotherapy.

Prognosis and surgical outcomes of the total thymectomy versus thymomectomy in non-myasthenic patients with early-stage thymoma: A systematic review and meta-analysis.

Whether thymectomy (TM) or thymomectomy (TMM) is better for non-myasthenic patients with early-stage thymoma. We conducted a meta-analysis to compare the clinical outcomes and prognoses of non-myasthenic patients with early-stage thymoma treated using thymectomy versus thymomectomy. PubMed, Embase, Cochrane Library and CNKI databases were systematically searched for relevant studies on the surgical treatment (TM and TMM) of non-myasthenic patients with early-stage thymoma published before March 2022. The Newcastle-Ottawa scale was used to evaluate the quality of the studies, and the data were analyzed using RevMan version 5.30. Fixed or random effect models were used for the meta-analysis depending on heterogeneity. Subgroup analyses were performed to compare short-term perioperative and long-term tumor outcomes. A total of 15 eligible studies, including 3023 patients, were identified in the electronic databases. Our analysis indicated that TMM patients might benefit from a shorter duration of surgery (p = 0.006), lower blood loss volume (p < 0.001), less postoperative drainage (p = 0.03), and a shorter hospital stay (p = 0.009). There were no significant differences in the overall survival rate (p = 0.47) or disease-free survival rate (p = 0.66) between the two surgery treatment groups. Likewise, TM and TMM were similar in the administration of adjuvant therapy (p = 0.29), resection completeness (p = 0.38), and postoperative thymoma recurrence (p = 0.99). Our study revealed that TMM might be a more appropriate option in treating non-myasthenic patients with early-stage thymoma.

Effect of preoperative radiotherapy on the prognosis of patients with stage cTxN0M0 esophageal squamous cell carcinoma: propensity score matching analysis based on SEER database.

Objective: The aim of this study was to investigate the effect of preoperative radiotherapy (RT) on overall survival (OS) in patients with stage cTxN0M0 esophageal squamous cell carcinoma (ESCC). Methods: A total of 467 patients with ESCC diagnosed as cTxN0M0 and undergoing esophagectomy between 2004 and 2016 were downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. According to the presence or absence of preoperative RT, the patients were divided into preoperative RT group and non-preoperative RT group. Propensity score matching (PSM) was performed to equalize baseline levels between groups. Univariate and multivariate Cox regression analyses were used to compare the survival differences between the two groups. Results: Using PSM, 162 pairs of patients were selected. Preoperative RT was not a prognostic factor for OS in all patients with cTx stage. After PSM, for patients with cT1-2 stage, univariate Cox regression analysis showed that preoperative RT was an influencing factor of OS, and multivariate Cox regression analysis confirmed that preoperative RT was an independent predictor of OS. Compared with non-preoperative RT, preoperative RT significantly decreased OS (HR = 1.556, 95%CI 1.008-2.464, p = 0.046). For patients with cT3-4, univariate Cox regression analysis showed that preoperative RT was an influencing factor for OS, and multivariate Cox regression analysis determined that preoperative RT was independent predictors of survival. Compared with non-preoperative RT, preoperative RT significantly improved the OS (HR = 0.479, 95%CI 0.272-0.841, p = 0.010). Conclusion: For ESCC, preoperative RT can improve the OS of patients with cT3-4N0M0. However, preoperative RT is not suitable for patients with cT1-2N0M0.

Efficacy and safety of immune checkpoint inhibitors versus chemotherapy in the second-line treatment of advanced esophageal squamous cell carcinoma: a meta-analysis and systematic review.

Background: Esophageal cancer (EC) is the seventh most common cancer in the world, with 604,000 new cases diagnosed each year. Immune checkpoint inhibitors (ICIs) including programmed death ligand-1 (PD-L1) inhibitors have demonstrated a considerable survival advantage over chemotherapy in numerous randomized controlled trials (RCTs), particularly in patients with advanced esophageal squamous cell carcinoma (ESCC). In this analysis, we aimed to demonstrate that ICIs are more safe and effective than chemotherapy when used as a second-line treatment for advanced ESCC. Methods: Publications on the safety and efficiency of ICIs in advanced ESCC that were available prior to February 2022 were searched in the Cochrane Library, Embase, and PubMed databases. Studies with missing data were eliminated, and studies that compared the treatments between the immunotherapy group and chemotherapy group were included. Statistical analysis was carried out using RevMan 5.3, and risk and quality were evaluated with relevant evaluation tools. Results: Five studies met the inclusion criteria were selected, involving 1,970 patients with advanced ESCC. We compared chemotherapy and immunotherapy in the second-line treatment of advanced ESCC. ICIs considerably enhanced both the objective response rate (P=0.007) and overall survival (OS; P=0.001). However, the effect of ICIs on progression-free survival (PFS) was not significant (P=0.43). ICIs presented fewer grade 3-5 treatment-related adverse events (TRAEs), and there was also a suggested linkage between both PD-L1 expression and the effectiveness of the therapeutic intervention. Conclusions: For patients with advanced ESCC, ICIs are more effective and safer than chemotherapy, and thus have a higher treatment value.

Minimally invasive versus open esophagectomy after neoadjuvant therapy for esophageal cancer: a meta-analysis.

OBJECTIVES: Neoadjuvant therapy and minimally invasive esophagectomy (MIE) are widely used in the comprehensive treatment of esophageal cancer. This study aimed to investigate the advantages of MIE for esophageal cancer after neoadjuvant therapy. METHODS: Published clinical studies were reviewed and survival data and safety data were extracted. We compared the long-term survival and safety of MIE versus open esophagectomy after neoadjuvant surgery in a series of meta-analyses. RESULTS: 6 retrospective studies were included. Overall, MIE could significantly improve the overall survival of patients with esophageal cancer after neoadjuvant therapy compared with open esophagectomy [hazard ratio (HR) = 0.86, 95% confidence interval (CI) (0.75, 0.98)]. Compared with open esophagectomy, MIE could significantly reduce intraoperative blood loss and operative time [mean difference (MD) = -40.28.78, 95% CI (- 62.98, - 17.58); MD = -28.78, 95% CI (- 42.48, - 15.07), respectively]. There was no significant difference in 30-day and 90-day mortality between MIE and open esophagectomy [odds ratio (OR) = 0.42, 95% CI (0.09, 2.01); OR 0.80, 95% CI (0.25, 2.60), respectively]. MIE could not significantly reduce the incidence of anastomotic leakage, recurrent laryngeal nerve palsy and chylothorax [OR 0.70, 95% CI (0.37, 1.32); OR 1.43, 95% CI (0.33, 6.25); HR = 1.79, 95% CI (0.67, 4.75), respectively], but the incidence of pneumonia was significantly reduced [HR = 0.43, 95% CI (0.22, 0.82)]. In addition, the length of hospital stay and the incidence of total complications were significantly reduced after MIE [MD = -2.61, 95% CI (- 3.10, - 2.12); HR = 0.66, 95% CI (0.45, 0.98), respectively]. CONCLUSION: MIE after neoadjuvant therapy is effective and safe. Compared with open esophagectomy, MIE can improve the long-term survival and reduce the incidence of postoperative complications of esophageal cancer patients.

Survival Outcomes of Sublobectomy and Lobectomy in Elderly Patients with Peripheral Solid-Dominant Non-small Cell Lung Cancer.

BACKGROUND: According to the JCOG0802 study, there were many non-cancer-related deaths in the lobectomy group. Meanwhile, the median age of the enrolled patients in the JCOG0802 study was 67 years old. Whether this difference in perioperative outcomes and survival outcomes is related to age remains unknown. We aim to investigate whether the sublobectomy was comparable to lobectomy in elderly (≥ 75 years old) patients with peripheral solid-dominant [50% ≤ consolidation tumor ratio (CTR) ≤ 1] and diameter ≤ 2 cm non-small cell lung cancer (NSCLC). METHODS: We retrospectively included 10,830 patients who underwent surgery treatment at two large-volume medical centers, Taizhou Hospital of Zhejiang Province and Shanghai Chest Hospital, from January 2016 to January 2018. Of these, 164 patients aged ≥ 75 years, tumor ≤ 2 cm, and 50% ≤ CTR ≤ 1 who received lobectomy or sublobectomy were included in our study. The perioperative outcomes, survival analyses, analysis of death patterns, tumor recurrence patterns, and Cox regression analyses were performed. RESULTS: On perioperative outcomes, sublobectomy was associated with a shorter operation time (p < 0.001), and in terms of survival outcomes, the 5-year overall survival (OS, p = 0.85) and 5-year disease-free surivial (DFS, p = 0.58) did not differ significantly between the two groups. The Cox regression analyses showed that CTR value, visceral pleural infiltration, and smoking were independent risk factors for worse OS. Furthermore, tumor recurrence pattern and death patterns between the two groups did not differ significantly. CONCLUSIONS: Sublobectomy could achieve superior perioperative outcomes and equivalent oncological efficacy in comparison with lobectomy in elderly patients (≥ 75 years old) with peripheral solid-dominant and diameter ≤ 2 cm NSCLC.

Prognosis of patients with esophageal squamous cell carcinoma undergoing surgery versus no surgery after neoadjuvant chemoradiotherapy: a retrospective cohort study.

Background: Esophageal surgery is an invasive surgical method with high surgical risk, and seriously affects postoperative quality of life. This study compared the prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (Neo-CRT) plus surgery and Neo-CRT alone, in order to explore the necessity of continuing operation after Neo-CRT. Methods: We retrospectively analyzed 223 patients who received Neo-CRT in Taizhou Hospital Affiliated to Wenzhou Medical University from June 2007 to December 2014. According to the treatment, the patients were divided into Neo-CRT plus surgery group (operation group, n=185) and single Neo-CRT group (non-operation group, n=38). Patients in both groups were followed up for a long time until death or deadline. The overall survival (OS), adverse reactions, recurrence and death results of the two groups were evaluated. The risk factors of poor prognosis were analyzed. Results: The two groups were comparable. The median follow-up time was 23.5 months in non-operation group and 112.9 months in operation group. The 1-year survival rate, 2-year survival rate and 5-year survival rate in non-operation group were 69.9%, 47.7% and 31.8%, respectively. The rates in operation group were 94.0%, 79.3% and 65.0%, respectively. The incidence of low hemoglobin was 73.7% (non-operation group) and 53.0% (operation group). The infection rates were 15.8% and 2.7%, respectively. There was no significant difference in the incidence of leukopenia, neutropenia and thrombocytopenia between the two groups. Multivariate analysis showed that recurrence and treatment were independent risk factors affecting the prognosis of patients. Conclusions: To sum up, no matter in terms of recurrence rate or OS rate, the prognosis of patients in the operation group was better than that in the non-operation group. Therefore, Neo-CRT combined with esophagectomy is recommended for locally advanced ESCC with acceptable surgical risk.

Lithium Bonds Enable Small Biomass Molecule-Based Ionoelastomers with Multiple Functions for Soft Intelligent Electronics.

Lipoic acid (LA), which originates from animals and plants, is a small biomass molecule and has recently shown great application value in soft conductors. However, the severe depolymerization of LA places a significant limitation on its utilization. A strategy of using Li-bonds as both depolymerization quenchers and dynamic mediators to melt transform LA into high-performance ionoelastomers (IEs) is proposed. They feature dry networks while simultaneously combining transparency, stretchability, conductivity, self-healing ability, non-corrosive property, re-mouldability, strain-sensitivity, recyclability, and degradability. Most of the existing soft conductors' drawbacks, such as the tedious synthesis, non-renewable polymer networks, limited functions, and single-use only, are successfully solved. In addition, the multi-functions allow IEs to be used as soft sensors in human-computer interactive games and wireless remote sports assistants. Notably, the recycled IE also provides an efficient conductive filler for transparent ionic papers, which can be used to design soft transparent triboelectric nanogenerators for energy harvesting and multidirectional motion sensing. This work creates a new direction for future research involving intelligent soft electronics.

Lymph node micrometastasis in non-small cell lung cancer.

Lung cancer has some of the highest morbidity and mortality rates of all cancers, and an important risk factor for mortality in patients with lung cancer is tumor metastasis. Even if a tumor is completely removed at an early stage of the disease, quite a number of patients still have the risk of recurrence. With the advent of molecular diagnostic and therapeutics, more and more studies have found that a poor prognosis may be related to lymph node micrometastasis. However, clinicians still find that predicting the prognosis and choosing the type of surgery and postoperative adjuvant chemotherapy are still challenging. Thus, this article reviews the current research status of lymph node micrometastasis in non-small cell lung cancer, envision to provide some updates and insights in this area.

Silencing of A-kinase anchor protein 4 inhibits the metastasis and growth of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most malignant tumors. The treatment of advanced NSCLC can be challenging due to drug resistance. The discovery of novel cancer-testis antigens to develop new strategies for advanced metastatic NSCLC is required. AKAP4 is an oncogene discovered in some malignant tumors, and its molecular function of AKAP4 in NSCLC is unknown. This study aimed to explore the potential function of AKAP4 in the development and progression of NSCLC. AKAP-4 was found to be significantly upregulated in both clinical NSCLC tissues and NSCLC cell lines. Cell viability and migration were suppressed, apoptosis was induced, and tube formation was inhibited by the knockdown of AKAP-4, accompanied by the downregulation of VEGF, N-cadherin, EphA2, and MMP-2, and upregulation of c-AMP, PKA, and E-cadherin. In vivo xenograft experiments revealed that tumor growth was inhibited by the knockdown of AKAP4, accompanied by the activation of c-AMP/PKA signaling and inhibition of epithelial-mesenchymal transition progression. Our results show that AKAP4 might be an important target for treating NSCLC because of its function in promoting the migration and proliferation of NSCLC cells.

Neoadjuvant chemoradiotherapy, chemotherapy, and radiotherapy do not significantly increase the incidence of anastomotic leakage after esophageal cancer surgery: a meta-analysis.

This study investigated whether neoadjuvant therapies, such as neoadjuvant chemoradiotherapy (NCRT), neoadjuvant chemotherapy (NCT), and neoadjuvant radiotherapy (NRT), would affect the incidence of anastomotic leakage (AL) after esophageal cancer surgery. Published randomized controlled trials were reviewed, and the incidence of AL after esophageal cancer was statistically analyzed in each study. Meta-analysis was performed using Revman and Stata software. A total of 17 randomized controlled trials with 2874 patients were reviewed showing that, in general, preoperative neoadjuvant therapies were not significant risk factors for AL after esophageal cancer surgery (relative risk [RR] = 0.82, 95% CI = 0.64-1.04). NCRT and NRT did not significantly increase the risk of postoperative AL in patients with esophageal cancer (RR = 0.81, 95% CI = 0.63-1.05; RR = 0.64, 95% CI = 0.14-2.97, respectively). Moreover, NCT has no significant correlation with the occurrence of AL (RR = 1.01, 95% CI = 0.57-1.80). NCRT, NCT, and NRT do not significantly increase the incidence of gastroesophageal AL after esophageal cancer surgery.

(Neo)adjuvant Chemoradiotherapy is Beneficial to the Long-term Survival of Locally Advanced Esophageal Squamous Cell Carcinoma: A Network Meta-analysis.

PURPOSE: To determine the most effective and safest treatment mode for locally advanced resectable esophageal squamous cell carcinoma through a network meta-analysis. METHOD: A Bayesian model was used for a network meta-analysis comparing the efficacy and safety of surgery alone, neoadjuvant therapy, and adjuvant therapy. RESULTS: Thirty clinical studies, including thirty-one articles, 4866 patients, were analyzed. Overall survival rate: Adjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy were significantly advantageous over surgery alone [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57-0.93; HR 0.75, 95%CI 0.65-0.86]. There was no statistically significant difference between adjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy [HR 0.97, 95%CI 0.75-1.28]. Disease-free survival rate: Compared with surgery alone, neoadjuvant chemoradiotherapy had significant benefits [HR 0.65, 95%CI 0.53-0.78]; adjuvant chemoradiotherapy had similar, but not significant benefits [HR 0.7, 0.95%CI 0.45-1.06]. The difference between neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy was also not statistically significant [HR 0.94, 0.95%CI 0.61-1.43]. Surgery after neoadjuvant chemoradiotherapy: The R0 resection rate was significantly improved [relative risk (RR) 0.25, 95%CI 0.07-0.86], but the overall postoperative morbidity rate and 30-day postoperative mortality rate tended to increase [RR 1.27, 95%CI 0.8-2.01; RR 1.59, 95%CI 0.7-3.22]. Neither neoadjuvant chemotherapy nor neoadjuvant radiotherapy significantly altered the surgical safety or R0 resection rate. CONCLUSION: Both neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy appear to be the best supplements to surgery for locally advanced resectable esophageal squamous cell carcinoma.

Efficacy and Safety of Neoadjuvant Targeted Therapy vs. Neoadjuvant Chemotherapy for Stage IIIA EGFR-Mutant Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Purpose: The role of targeted therapy in the neoadjuvant field of stage IIIA epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is still controversial. We sought to evaluate the efficacy and safety of neoadjuvant targeted therapy (NTT) with neoadjuvant chemotherapy (NCT) used as a benchmark comparator. Methods: A systematic search was conducted in four databases (Pubmed, Cochrane Library, Embase, CNKI) for eligible studies on NTT published before October 2020. The primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade 3/4 adverse events (AEs). Statistical analysis and bias assessment were performed by RevMan 5.3. Results: A total of 319 patients, including 3 randomized controlled trials and 2 non-randomized controlled trials, were included in the meta-analysis. Perform the second subgroup analysis after excluding 2 non-randomized controlled trials. The meta-analysis reveals that, for EGFR mutation-positive stage IIIA NSCLC patients, compared with NCT, NTT can significantly increase ORR (relative risk [RR]:1.70, 95% confidence interval [CI]:1.35-2.15; subgroup-RR:1.56, 95% CI 1.23-2.0) and significantly reduce grade 3/4 AEs (RR:0.5, 95% CI 0.34-0.75; subgroup-RR: 0.53, 95% CI 0.26-1.08). The OS of the NTT arm is slightly higher, but the difference is not significant (hazards ratio [HR]: 0.74, 95% CI: 0.43-1.27; subgroup-HR: 0.64 95% CI 0.40-1.03). No difference in PFS was found (HR: 0.81, 95% CI 0.27-2.44). Conclusion: In neoadjuvant setting, targeted therapy has a definitive effect on patients with EGFR mutation-positive stage IIIA NSCLC and is even better than chemotherapy in terms of toxicity and tumor response rate. Systematic Review Registration: PROSPERO, identifier CRD42021221136.

Narrative review of pembrolizumab for the treatment of esophageal cancer: evidence and outlook.

OBJECTIVE: Based on the current evidence, review the efficacy and safety profile of pembrolizumab, along with its shortcomings, in an effort to define future research directions. BACKGROUND: The survival outcome of esophageal cancer (EC) is poor, especially in patients with advanced stage. Palliative surgery, chemotherapy, radiotherapy and chemoradiotherapy have limited efficacy in prolonging the survival time. Currently, immunotherapies, including adoptive cell therapy-based, antibody-based, and vaccine-based therapies, are attracting considerable attention. The mechanism of immunotherapy lies in the modification of immune response and prevention of immune escape. Immunomodulatory agents can block the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway, thereby allowing lymphocytes to attack tumor cells. This class of drugs has the potential to treat a variety of tumors and may substantially improve overall survival (OS) in some patients. Multiple clinical trials have shown that pembrolizumab has good efficacy and safety, enhances the EC treatment paradigm, and has even become the first-line treatment of choice for patients with PD-L1-positive recurrent or metastatic EC. METHODS: We reviewed the results of clinical trials of pembrolizumab for EC and gastroesophageal cancer presented at Embase, PubMed, the American Society of Clinical Oncology (ASCO) annual meetings, and the Cochrane Central Register of Controlled Trials. CONCLUSIONS: Pembrolizumab has good efficacy and tolerability profiles, and has emerged as a second-line option for the treatment of PD-L1-positive locally advanced or metastatic ESCC. Pembrolizumab has many promising applications, and further investigations into its mechanisms should be conducted.

Efficacy and Benefit of Postoperative Chemotherapy in Micropapillray or Solid Predominant Pattern in Stage IB Lung Adenocarcinoma: A Systematic Review and Meta-Analysis.

Background: The benefit of postoperative chemotherapy remains controversial for patients with either a micropapillary or solid pattern in stage IB non-small cell lung cancer. This study is designed to explore the significance of postoperative chemotherapy in patients with either a micropapillary or solid pattern in stage IB lung adenocarcinoma. Method: To conduct the meta-analysis, PubMed, Cochrane Library, Embase and Medline were used to collect literature on long-term follow-up studies published before March, 2021, involving postoperative chemotherapy for patients with both a micropapillary or solid pattern in stage IB lung adenocarcinoma as compared to non-postoperative chemotherapy. Survival data was extracted from the literature, including the overall survival and disease-free survival. Based on overall survival and disease-free survival, hazard ratios and their 95% of confidence intervals were applied to assess the prognostic effect of postoperative chemotherapy. Review Manager software was used to merge the effect size for the meta-analysis. Result: In total, 6 papers with 956 patients were included. In terms of the prognosis of patients suffering from lung cancer when receiving postoperative chemotherapy, this study comprehensively reviews and evaluates the available evidence of micropapillary or solid patterns. After excluding the heterogeneity between the studies, we found that the pooled results from 6 studies report that postoperative chemotherapy was associated with a better overall survival rate when compared with non-postoperative chemotherapy (hazard ratio = 0.58, 95% confidence interval, 0.44-0.77; P = 0.0002). Postoperative chemotherapy also significantly improved the disease-free survival in patients with either a micropapillary or a solid pattern in stage IB lung adenocarcinoma (postoperative chemotherapy vs. non-postoperative chemotherapy, hazard ratio = 0.51, 95% confidence interval, 0.40-0.64; P < 0.001). However, a subgroup analysis showed that compared with non-postoperative chemotherapy, tumor size was unrelated to the prognosis of patients in stage IB undergoing postoperative chemotherapy (hazard ratio = 0.98, 95% confidence interval, 0.94-1.02; P = 0.27). Conclusion: Postoperative chemotherapy results in a better long-term survival rate for patients with either a solid or a micropapillary pattern in stage IB lung adenocarcinoma. Multi-center, prospective, clinical trials are needed to validate our findings.

PFKP is highly expressed in lung cancer and regulates glucose metabolism.

PURPOSE: Although it has been reported that up-regulation of phosphofructokinase (PFK) expression is a major feature of malignant tumors, the role of platelet type PFK (PFKP) in tumor initiation and progression is as yet poorly understood. The objective of this study was to evaluate PFKP expression in lung cancer and its effect on glycolysis, and to explore correlations between PFKP expression levels and clinical lung cancer patient features. METHODS: PFKP mRNA expression levels in cancer tissues and adjacent normal tissues were compared using The Cancer Genome Atlas (TCGA) database. PFKP mRNA and protein expression levels in fresh lung cancer tissues and cell lines were assessed using quantitative real-time PCR and Western blotting. Immunohistochemistry (IHC) was used to assess PFKP expression in 150 archival lung adenocarcinoma samples, after which follow-up data and their correlations with clinical features and patient prognosis were evaluated. A retroviral shRNA-mediated method was used to construct stable cell lines expressing low levels of PFKP. Glucose, lactate and adenosine triphosphate concentrations in the cell culture supernatants were determined using enzymatic, spectrophotometric and enzyme-linked immunosorbent (ELISA) assays, respectively. The effect of PFKP expression on the proliferation of lung cancer cells was assessed using colony forming, MTT and flow cytometry assays, respectively. Finally, data from tissue samples of 533 patients with lung adenocarcinoma and 502 patients with lung squamous cell carcinoma were downloaded from the TCGA database, after which pathway and gene correlation information was retrieved using gene set enrichment analyses. RESULTS: We found that PFKP was highly expressed in lung cancer tissues and cell lines. Using IHC we found that PFKP was highly expressed in primary lung adenocarcinoma tissues and that a high expression was associated with a poor prognosis. Clinical data analysis revealed that the PFKP expression levels correlated with tumor size and patient survival. Lung cancer cell lines with decreased PFKP expression levels showed significant decreases in glucose uptake rates, lactate levels and adenosine triphosphate concentrations. They also exhibited significantly decreased proliferation rates, colony forming abilities and increased G2/M cell cycle phase percentages. Gene set enrichment analysis revealed that multiple pathways, including glycolytic pathways, may be involved in the regulation PFKP. CONCLUSIONS: Our data indicate that PFKP is highly expressed in lung cancer tissues and cell lines and is associated with tumor size and patient prognosis. As such, PFKP may serve as a prognostic biomarker. We also found that PFKP regulates the level of glycolysis in lung cancer cells and is associated with lung cancer cell proliferation. These data may be instrumental for the design of new lung cancer treatment options.