Comprehensive analysis the prognostic and immune characteristics of mitochondrial transport-related gene SFXN1 in lung adenocarcinoma.

BACKGROUND: Mitochondria, which serve as the fundamental organelle for cellular energy and metabolism, are closely linked to the growth and survival of cancer cells. This study aims to identify and assess Sideroflexin1 (SFXN1), an unprecedented mitochondrial gene, as a potential prognostic biomarker for lung adenocarcinoma (LUAD). METHODS: The mRNA and protein levels of SFXN1 were investigated based on the Cancer Genome Atlas (TCGA) LUAD dataset, and then validated by real-time quantitative PCR, Western Blotting and immunohistochemistry from our clinical samples. The clinical correlation and prognostic value were evaluated by the TCGA cohort and verified via our clinical dataset (n = 90). The somatic mutation, drug sensitivity data, immune cell infiltration and single-cell RNA sequencing data of SFXN1 were analyzed through public databases. RESULTS: SFXN1 was markedly upregulated at both mRNA and protein levels in LUAD, and high expression of SFXN1 were correlated with larger tumor size, positive lymph node metastasis, and advanced clinical stage. Furthermore, SFXN1 upregulation was significantly associated with poor clinical prognosis. SFXN1 co-expressed genes were also analyzed, which were mainly involved in the cell cycle, central carbon metabolism, DNA repair, and the HIF-1α signaling pathway. Additionally, SFXN1 expression correlated with the expression of multiple immunomodulators, which act to regulate the tumor immune microenvironment. Results also demonstrated an association between SFXN1 expression and increased immune cell infiltration, such as activated CD8 + T cells, natural killer cells (NKs), activated dendritic cells (DCs), and macrophages. LUAD patients with high SFXN1 expression exhibited heightened sensitivity to multiple chemotherapies and targeted drugs and predicted a poor response to immunotherapy. SFXN1 represented an independent prognostic marker for LUAD patients with an improved prognostic value for overall survival when combined with clinical stage information. CONCLUSIONS: SFXN1 is frequently upregulated in LUAD and has a significant impact on the tumor immune environment. Our study uncovers the potential of SFXN1 as a prognostic biomarker and as a novel target for intervention in LUAD.

Clinico-pathological characteristics of IGFR1 and VEGF-A co-expression in early and locally advanced-stage lung adenocarcinoma.

BACKGROUND: Although targeted therapies and immunotherapy have achieved significant clinical benefits in patients with certain pathological types of lung cancer. However, prognosis for patients with lung adenocarcinoma still remains unsatisfactory. It is of extremely importance to find ideal prognostic indicators to predict the prognosis of lung adenocarcinoma patients, especially for patients with early and locally advanced-stage lung adenocarcinoma. The purpose of this study is to elucidate the significance of Insulin-like growth factor receptor 1 (IGFR1) and Vascular endothelial growth factor A (VEGF-A) expression in predicting progression-free survival (PFS) and overall survival (OS) in patients with early and locally advanced-stage lung adenocarcinoma. METHODS: In this study, IGFR1 and VEGF-A expression on 119 specimens of patients early and locally advanced-stage lung adenocarcinoma were analyzed by immunohistochemistry with an H-score system. RESULTS: Both high IGFR1 expression and VEGF-A expression patients were resulted in 59 (49.6%) separately. The numbers and proportions of IGFR1-&VEGF-A- subgroup, IGFR1-&VEGF-A+ subgroup, IGFR1+&VEGF-A- subgroup and IGFR1+&VEGF-A+ subgroup are 23 (19.3%), 37 (31.1%), 37 (31.1%) and 22 (18.5%) respectively. High IGFR1 expression was significantly associated with both poor PFS and OS of all patients in a univariate analysis. Multivariable analysis showed that patients with IGFR1+&VEGF-A+ expression exhibited a worst PFS and OS in the subgroup of lung adenocarcinoma patients with EGFR mutation. CONCLUSIONS: These results suggest that IGFR1+&VEGF-A+ is expected to be a disadvantageous factor for prognosis in the subgroup of EGFR mutation in patients with early and locally advanced-stage lung adenocarcinoma. What's more, this study may provide the theoretical possibility to screen optimal population for a combination therapy with anti-VEGF and anti-IGFR1 in patients with early and locally advanced-stage lung adenocarcinoma.

Predictive and prognostic markers from endoscopic ultrasound with biopsies during definitive chemoradiation therapy in esophageal squamous cell carcinoma.

INTRODUCTION: Endoscopic ultrasound (EUS) may play a role in evaluating treatment response after definitive chemoradiation therapy (dCRT) for esophageal squamous cell carcinoma (ESCC). This study explored the prognostic markers of EUS with biopsies and developed two nomograms for survival prediction. METHODS: A total of 821 patients newly diagnosed with ESCC between January 2015 and December 2019 were reviewed. We investigated the prognostic value of the changes in tumor imaging characteristics and histopathological markers by an interim response evaluation, including presence of stenosis, ulceration, tumor length, tumor thickness, lumen involvement, and tumor remission. Independent prognostic factors of progression-free survival (PFS) and overall survival (OS) were determined using Cox regression analysis and further selected to build two nomogram models for survival prediction. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to respectively assess its discriminatory capacity, predictive accuracy, and clinical usefulness. RESULTS: A total of 155 patients were enrolled in this study and divided into the training (109 cases) and testing (46 cases) cohorts. Tumor length, residual tumor thickness, reduction in tumor thickness, lumen involvement, and excellent remission (ER) of spatial luminal involvement in ESCC (ER/SLI) differed significantly between responders and non-responders. For patients undergoing dCRT, tumor stage (P = 0.001, 0.002), tumor length (P = 0.013, 0.008), > 0.36 reduction in tumor thickness (P = 0.004, 0.004) and ER/SLI (P = 0.041, 0.031) were independent prognostic markers for both PFS and OS. Time-dependent ROC curves, calibration curves, and DCA indicated that the predicted survival rates of our two established nomogram models were highly accurate. CONCLUSION: Our nomogram showed high accuracy in predicting PFS and OS for ESCC after dCRT. External validation and complementation of other biomarkers are needed in further studies.

Effects of PEG in patients with esophageal squamous cell carcinoma during concurrent chemoradiotherapy: a prospective study.

BACKGROUND AND AIMS: This prospective study aimed to compare the changes in nutritional status and adverse events among patients with esophageal squamous cell carcinoma who received enteral nutrition through oral intake, PEG, and an enteral nasogastric tube (NGT) during concurrent chemoradiotherapy (CCRT). METHODS: Of 141 included patients, 38, 74, and 29 patients were fed through oral intake, PEG, and NGTs, respectively. The clinical characteristics and baseline nutritional status of the 3 groups were recorded and analyzed. The Patient-Generated Subjective Global Assessment score, skeletal muscle index, and quality of life were evaluated before and after CCRT; the incidence of adverse events during feeding using PEG and NGTs was also recorded. The correlations among the different nutritional pathways and the CCRT-related adverse events (eg, radiation esophagitis and myelosuppression) were assessed. RESULTS: At baseline, the oral intake group had a significantly better nutritional status and lower disease stage than those in the PEG and NGT groups. However, during CCRT, the oral intake group exhibited the most significant decreases in weight and skeletal muscle index. The synchronous chemotherapy completion rate was the highest in the PEG group. Multivariate analysis showed that the planning tumor volume and oral intake and NGT feeding pathways were associated with radiation esophagitis of at least grade 2. CONCLUSIONS: We found that PEG effectively maintained the body weight and skeletal muscle index of patients with esophageal cancer during CCRT. PEG also improved the synchronous chemotherapy completion rate and reduced the occurrence of at least grade 2 radiation esophagitis. (Clinical trial registration number: NCT04199832.).

Prognostic and immunological characteristics of CDK1 in lung adenocarcinoma: A systematic analysis.

Background: Cyclin-dependent kinases (CDKs) play a key role in cell proliferation in lung adenocarcinoma (LUAD). Comprehensive analysis of CDKs to elucidate their clinical significance and interactions with the tumor immune microenvironment is needed. Methods: RNA expression, somatic mutation, copy number variation, and single-cell RNA sequencing data were downloaded from public datasets. First, we comprehensively evaluated the expression profile and prognostic characteristics of 26 CDKs in LUAD, and CDK1 was selected as a candidate for further analysis. Then, a systematic analysis was performed to explore the relationships of CDK1 with clinical characteristics and tumor immune microenvironment factors in LUAD. Results: CDK1 was markedly upregulated at both the mRNA and protein level in LUAD. Moreover, overexpression of CDK1 was related to poor clinical outcomes. CDK1 coexpressed genes were mainly involved in the cell cycle, the DNA repair process, and the p53 signaling pathway. In addition, CDK1 expression was found to be correlated with the expression of multiple immunomodulators and chemokines, which participate in activating and suppressing the immune microenvironment. CDK1 expression was also correlated with increased infiltration of numerous immune cells, including CD4+ T cells and M1 macrophages. Patients with high CDK1 expression tended to have a poor response to immunotherapy but were sensitive to multiple chemotherapies and targeted drugs. The MDK-NCL and SPP1-CD44 ligand-receptor pairs were markedly activated in the intercellular communication network. CDK1 was an independent prognostic factor for LUAD and improved the ability to predict overall survival when combined with tumor stage. Conclusion: CDK1 plays an essential role in reshaping the tumor immune microenvironment and might be a prognostic and treatment biomarker in LUAD.

Radiotherapy plus camrelizumab affects peripheral CD8 T-cell differentiation subsets expressing PD-1, TIGIT, and CTLA-4 in esophageal squamous cell carcinoma.

Our previous phase Ib trial (NCT03222440) showed that radiotherapy plus the anti-PD-1 antibody camrelizumab is a safe and feasible first-line therapy for locally advanced esophageal squamous cell carcinoma. In this study, we divided peripheral CD8 T-cell differentiation subsets into 4 subpopulations (naive T cells, central memory T cells, effector memory T cells, and CD45RA+ effector memory T cells). We then investigated the influence of radiotherapy plus camrelizumab therapy on the proportions of the 4 subsets and their PD-1, TIGIT, and CTLA-4 expression as well as their proliferative activity and compared the effects with those of concurrent chemoradiotherapy. Nineteen and 15 patients with esophageal squamous cell carcinoma who received radiotherapy plus camrelizumab therapy and concurrent chemoradiotherapy, respectively, were enrolled in this study. We isolated peripheral blood mononuclear cells from these patients before treatment and longitudinally after the delivery of 40 Gy radiotherapy. Flow cytometry was conducted to detect peripheral CD8 T-cell subsets and PD-1, TIGIT, CTLA-4, and Ki67 expression levels in patients with esophageal squamous cell carcinoma. We found that radiotherapy plus camrelizumab therapy did not change the proportions of the 4 subsets or the expression of CTLA-4, but this therapy decreased PD-1 expression by the 4 subsets and TIGIT expression by effector memory T cells, as well as significantly enhanced the proliferative activity of CD8 T cells, whereas concurrent chemoradiotherapy produced different effects. In addition, we further identified peripheral biomarkers that potentially predict the outcome of radiotherapy plus camrelizumab therapy.

A Clinical Scoring Model to Predict the Effect of Induction Chemotherapy With Definitive Concurrent Chemoradiotherapy on Esophageal Squamous Cell Carcinoma Prognosis.

PURPOSE: The aim of the study was to compare the clinical outcomes of induction chemotherapy (IC) followed by definitive concurrent chemoradiotherapy (dCCRT) versus chemoradiotherapy alone in patients with esophageal squamous cell carcinoma (ESCC) on the basis of a clinical scoring model. METHODS: A retrospective review of 599 patients with ESCC treated with dCCRT at our institution from 2010 to 2019 was conducted. The patients were divided into two groups based on whether they received IC. A clinical scoring model was performed using the significant variables obtained from the multivariate analysis. The PFS and OS rates were estimated using the Kaplan-Meier method. RESULTS: During the study period, 182 patients receiving IC followed by dCCRT and 417 dCCRT alone were identified. No significant differences in the PFS and OS rates were observed between the IC group (P=0.532) and the non-IC group (P=0.078). A clinical scoring model was constructed based on independent prognostic factors with scores ranging from 0 to 10.4. The patients were divided into high- and low-risk groups by using the median score as the cutoff value. The PFS rate of patients receiving IC was higher than that of patients treated without IC (P=0.034), while there was no improvement in the OS rate (P=0.794) in the high-risk group. No significant differences in the PFS (P=0.207) or OS (P=0.997) rate were found between the two treatment groups in the low-risk group. CONCLUSIONS: The addition of IC followed by dCCRT for patients with ESCC might be associated with better PFS rates based on a clinical scoring model but has no impact on OS rates. Further prospective studies are warranted for the validation of this model.

Annual report of the esophageal cancer radiation group of the Department of Radiotherapy, Tianjin Medical University Cancer Institute & Hospital.

BACKGROUND: This report describes the clinical work in esophageal cancer radiation group at the Department of Radiotherapy, Tianjin Medical University Cancer Institute & Hospital (TJMUCH). METHODS: We retrospectively analyzed the clinical data of patients with esophageal cancer who received radiotherapy (RT) at TJMUCH during the 5-year period between 2015 and 2019, including RT procedures, RT methods, treatment types, treatment outcomes and complications, and clinical trials. RESULTS: In 2015-2019, 1,464 patients with esophageal cancer received RT at the Department of Radiotherapy, TJMUCH. Of these, 1,176 patients received definitive chemoradiotherapy (CRT), 100 received preoperative neoadjuvant CRT, 120 received postoperative adjuvant RT, 49 received post-relapse RT, and 19 received palliative RT for advanced esophageal cancer. Among the patients who received definitive CRT, the incidences of grade 2 and higher radiation esophagitis, radiation pneumonitis, and leukopenia were 19.4%, 3.6%, and 19.7%, respectively; the incidences of grade 3-4 radiation esophagitis, radiation pneumonitis, and leukopenia were 9.4%, 1.2%, and 5.4%, respectively; no grade 5 acute adverse events were observed. Esophageal fistula was the major side effect during the advanced stage of RT. In 2015-2018, 44 patients (5%, 44/846) developed esophageal fistula; of these, 34 cases occurred after RT, and 10 cases occurred during RT. The overall survival was based on the data of 544 patients with esophageal cancer who underwent definitive RT at TJMUCH between March 2010 and September 2016. The median follow-up time was 21.6 months. The median survival was 19.6 months; and the 1-, 3-, and 5-year overall survival rates were 69.4%, 37.2%, and 32.3%, respectively. In 2015-2019, approximately 201 patients participated in different prospective clinical trials. CONCLUSIONS: RT is a crucial and effective treatment for esophageal cancer. Standardized treatment procedures, multidisciplinary cooperation, are the foundations for good treatment effects. Many promising ongoing clinical trials will be helpful to improve the prognosis and survival of esophageal cancer patients in the future.

The efficacy and safety of simultaneous integrated dose reduction in clinical target volume with intensity-modulated radiotherapy for patients with locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Compelling research to explore the effectiveness of simultaneous integrated dose reduction in clinical target volume (CTV) with intensity-modulated radiotherapy (SIR-IMRT) for locally advanced esophageal squamous cell carcinoma (ESCC) are limited. This study aimed to compare the clinical efficacy and treatment-related toxicity between SIR-IMRT and conventional IMRT (C-IMRT) in the treatment of ESCC. METHODS: From March 2010 to September 2016, the clinical data of 257 patients with ESCC who received definitive IMRT in the Tianjin Medical University Cancer Institute and Hospital were collected and retrospectively analyzed. Among these patients, 137 patients received C-IMRT with a prescribed dose of 60 Gy in 30 fractions for planning target volume (PTV), while 120 patients received SIR-IMRT with a prescribed dose of 60 Gy in 30 fractions for the planning gross tumor volume (PGTV) and a prescribed dose of 54 Gy in 30 fractions for PTV. All of the patients received definitive IMRT with elective nodal irradiation. Locoregional control, survival, treatment toxicity and dose to organs at risk (OAR) were compared between the groups. RESULTS: Patients who received SIR-IMRT showed a similar locoregional failure rate compared to the C-IMRT group (27.5% versus 29.9%, P=0.668). The 1-, 2- and 3-year overall survival (OS) rates were 71.5%, 44.3%, 44.3% vs. 77.9%, 52.1%, 32.9% in the C-IMRT and SIR-IMRT groups, respectively (P=0.825). No significant differences were observed in PFS and LRRFS between the two groups (P=0.880 and P=0.216, respectively). The dose of lung V30 and the maximum dose of spinal cord in the C-IMRT group were significantly higher than those in the SIR-IMRT group (P=0.013, P=0.047). The incidence of acute radiation esophagitis was significantly lower in the SIR-IMRT group (P=0.046), although no statistical difference was observed in the incidence of acute severe adverse events between the two groups. CONCLUSIONS: SIR-IMRT offers an effective and safe option for patients with unresectable ESCC who receive definitive RT. Further prospective and larger sample size studies are warranted to confirm our results.