Growth charts for children aged 6-17 years in Shanxi, China: comparison with other cities of China and WHO.

BACKGROUND: Growth charts are an important method for evaluating a child's health, growth, and nutritional status. It is essential to monitor the growth of children and adolescents using growth charts. OBJECTIVES: To present body mass index (BMI)-for-age references reflecting children's growth in Shanxi. We also compare our new data with growth references of other cities of China and World Health Organization (WHO) growth standards. METHODS: A stratified cluster random sampling method was used to recruit 5461 children and adolescents aged 6-17 years. Height and weight were measured and BMI was calculated. The LMS method was used to calculate the percentile values of body mass index by sex and age. Smoothed BMI-for-age growth curves were presented for both sexes and compared with reference data from other cities of China and WHO. RESULTS: BMI centiles increased with age but with different patterns in both boys and girls. The centile curves from the 3rd to the 50th had a slight increase, while a sharp increase was seen from 11 to 17 years in boys and from 6 to 14 years in girls in the higher centiles. In comparison with other cities of China, the values for the 50th percentile are higher than those reported for children from China 2009, Shanghai, Changsha and China 2010 in both sexes. In comparison with WHO growth references, Chinese girls and boys had higher values in all percentiles, whereas curves of girls look roughly the same. The medians for BMI in Shanxi increase linearly from 6 to 17 years in boys. CONCLUSIONS: The BMI percentiles of children aged 6-17 years in Shanxi differed significantly from the growth reference curves of other cities of China and WHO. Recommending the provision of BMI reference curves for local children and adolescents to assess their growth and development and monitor their nutritional status. Early detection of overweight and obesity in children provides a scientific basis for the prevention and control of overweight and obesity in children.

Comprehensive bioinformatics analysis identifies lncRNA HCG22 as a migration inhibitor in esophageal squamous cell carcinoma.

Esophageal cancer is one of the most lethal malignancies worldwide, and esophageal squamous cell carcinoma (ESCC) is the dominant histological type. However, the long noncoding RNA (lncRNA) alterations in ESCC have not been elucidated to date. In this study, reliable databases from Gene Expression Omnibus (GEO), which analyzed lncRNA expression in ESCC tumor tissues and adjacent normal tissues were searched, and common differentially expressed lncRNAs and genes were analyzed. Next, cis- trans analysis was performed to predict the underlying relationships between altered lncRNAs and mRNAs, and the lncRNA-mRNA regulatory network was established. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of altered lncRNA-related genes were performed. The promising lncRNA HCG22 was validated by quantitative polymerase chain reaction (qPCR), and clinicopathological data were collected to identify the relationship between lncRNA HCG22 expression level and clinical features. Finally, Transwell assays were performed to explore the biological functions of lncRNA HCG22 in ESCC cells. Two hundred forty-one lncRNAs and 835 mRNAs were observed to be remarkably altered between ESCC tumor tissues and adjacent normal tissues. The lncRNA-mRNA regulatory network showed the coexpression association between lncRNA HCG22 and SPINK7 and ADAMTS12. GO and KEGG analyses showed that HCG22 and ADAMTS12 had potential biological functions in the cell migration of ESCC. The downregulation of lncRNA HCG22 in ESCC tumor tissues was validated by qPCR, and the clinicopathological data showed a noticeable correlation between lncRNA HCG22 expression level and the ESCC differentiational degree and clinical TNM stage. Kaplan-Meier analysis showed that patients with ESCC having low lncRNA HCG22 expression in ESCC tissues had considerably shorter overall survival compared with patients with ESCC having high lncRNA HCG22 expression. Following Transwell assays confirmed the migratory role of lncRNA HCG22 in ESCC cells. In conclusion, lncRNA HCG22 was downregulated in ESCC tissues and can be a migration inhibitor of ESCC cells, and SPINK7 and ADAMTS12 are promising to be the regulatory targets of lncRNA HCG22.

Phenotypic analysis of tumor-infiltrating lymphocytes from non-small cell lung cancer and their potential application for adoptive cell therapy.

AIM: Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) has demonstrated clinical benefits in metastatic melanoma treatment. However, the clinical application of TILs produced by a widely used standard protocol from non-small cell lung cancer (NSCLC) can be quite challenging because of the limited clinical benefits. A comprehensive phenotypic knowledge of TILs obtained from NSCLC is important for the development and improvement of personalized TIL therapy for NSCLC patients. METHODS: In this study, we successfully expanded TILs from 141 NSCLC tissues which can be used in clinical ACT after expansion by a rapid expansion protocol (REP). RESULTS: Our study indicates that the clinicopathological characteristics of patients have considerable impacts on the phenotype of in vitro TIL culture products. Different culture conditions are necessary for patients with different clinical features. Specific manipulations before REP expansion are required depending on the different phenotypes of TIL cultures (e.g. depletion of immune-suppressive γδT cells). With these optimizations, next-generation TIL therapy may become a treatment alternative for NSCLC patients in the future.

MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/ß-catenin axis in non-small-cell lung cancer.

MicroRNAs have been reported to play critical roles in the regulation of non-small-cell cancer (NSCLC) development, but the role of microRNA (miR)-331-3p in NSCLC is still unclear. In this study, the expression levels of miR-331-3p in NSCLC tumor tissues and adjacent normal tissues were examined by quantitative RT-PCR, and the relationship between miR-331-3p expression and patient clinicopathological characteristics was analyzed. The effects of miR-331-3p on epithelial-mesenchymal transition (EMT), migration, and metastasis of NSCLC cells were determined in vitro and vivo. Direct functional targets of miR-331-3p were identified by luciferase reporter assay, western blot assay, immunohistochemical staining, and rescue assay. The downstream pathway regulated by miR-331-3p was identified by immunofluorescence, immunoprecipitation, and Rac1 activity examination. Our results showed that miR-331-3p was significantly downregulated in NSCLC tumor tissues and was correlated with clinicopathological characteristics, and miR-331-3p could be an independent prognostic marker for NSCLC patients. Furthermore, miR-331-3p significantly suppressed EMT, migration and metastasis of NSCLC cells in vitro and in vivo. Both ErbB2 and VAV2 were direct functional targets of miR-331-3p. The activities of Rac1, PAK1, and ß-catenin were regulated by miR-331-3p through ErbB2 and VAV2 targeting. These results indicated that miR-331-3p suppresses EMT, migratory capacity, and metastatic ability by targeting ErbB2 and VAV2 through the Rac1/PAK1/ß-catenin axis in NSCLC.

SH2B1 promotes epithelial-mesenchymal transition through the IRS1/ß-catenin signaling axis in lung adenocarcinoma.

Lung adenocarcinoma (LADC), the most prevalent type of human lung cancer, is characterized by many molecular abnormalities. SH2B1, a member of the SH2-domain containing family, have recently been shown to act as tumor activators in multiple cancers, including LADC. However, the mechanisms underlying SH2B1 overexpression are not completely understood. Here, we reported that SH2B1 expression levels were significantly upregulated and positively associated with EMT markers and poor patient survival in LADC specimens. Modulation of SH2B1 levels had distinct effects on cell proliferation, cell cycle, migration, invasion, and morphology in A549 and H1299 cells in vitro and in vivo. At the molecular level, overexpression of SH2B1 resulted in the upregulation of the EMT markers, especially induced ß-catenin accumulation and activated ß-catenin signaling to promote LADC cell proliferation and metastasis, while silencing SH2B1 had the opposite effect. Furthermore, ectopic expression of SH2B1 in H1299 cells increased IRS1 expression level. Reduced expression of IRS1 considerably inhibited H1299 cell proliferation, migration, and invasion which were driven by SH2B1 overexpression. Collectively, these results provide unequivocal evidence to establish that SH2B1-IRS1-ß-catenin axis is required for promoting EMT, and might prove to be a promising strategy for restraining tumor progression in LADC patients.

Analysis of risk factors and classification of aortic fistula after esophagectomy.

BACKGROUND: Aortic fistula after esophagectomy is a rare and serious complication. The aims of this study were to describe the causes of and classify the fistulas. MATERIALS AND METHODS: Between January 2008 and December 2017, a total of 1018 patients underwent esophageal resection, mainly for esophageal cancer; aortic fistula after esophagectomy was diagnosed in four patients. We perform a literature review through a database search for similar cases. Aortic fistulas may be classified into two types based on the site at which they occur in relation to the alimentary tract and area of anastomosis. Type 1 fistula occurs within the area of anastomosis, whereas type 2 fistula occurs above or below the anastomosis. The risk factors and clinical features associated with aortic fistulas are described, and comparison between the two types is made. RESULTS: Through a literature search, 39 cases were identified, of which 26 cases were classified as type 1, and 13 cases were classified as type 2. Of 13 patients (33.3%) who underwent emergent intervention, seven patients survived. Approximately 76.9% of aortic fistula were related to anastomotic fistula, which was more prevalent in type 1 aortic fistula than in type 2 (92% versus 50%, P = 0.005). There was no statistically significant difference in age, gender, side of thoracotomy, type of anastomosis, the postoperative day the hemorrhage occurred, warning hemorrhage, chest pain, or the outcome between the two types of fistula. CONCLUSIONS: Anastomotic fistula is the primary cause of type 1 aortic fistula after esophagectomy, and early diagnosis and intervention of aortic fistula can improve prognosis. This classification may be a useful guide in determining the approach for second-stage alimentary tract reconstruction.

Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition.

UNLABELLED: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide because of metastasis. Epithelial-mesenchymal transition (EMT) is widely considered to be crucial to the invasion-metastasis cascade during cancer progression. Actin-like 6A (ACTL6A) is initially verified important for cell proliferation, differentiation, and migration. In this study, we find that ACTL6A plays an essential role in metastasis and EMT of HCC. ACTL6A expression is up-regulated in HCC cells and tissues. A high level of ACTL6A in HCCs is correlated with aggressive clinicopathological features and is an independent poor prognostic factor for overall and disease-free survival of HCC patients. Ectopic expression of ACTL6A markedly promotes HCC cells migration, invasion, as well as EMT in vitro and promotes tumor growth and metastasis in the mouse xenograft model. Opposite results are observed when ACTL6A is knocked down. Mechanistically, ACTL6A promotes metastasis and EMT through activating Notch signaling. ACTL6A knockdown has the equal blockage effect as the Notch signaling inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butylester, in HCC cells. Further studies indicate that ACTL6A might manipulate SRY (sex determining region Y)-box 2 (SOX2) expression and then activate Notch1 signaling. CONCLUSIONS: ACTL6A promotes metastasis and EMT by SOX2/Notch1 signaling, indicating a prognostic biomarker candidate and a potential therapeutic target for HCC.

MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths owing to its high rate of postoperative recurrence and metastasis. New research is continuously identifying novel metastasis-associated oncogenes and tumor suppressor genes. miRNAs are noncoding RNAs that regulate protein synthesis post-translationally. miR-130b is one of several miRNAs involved in tumor metastasis. However, the role of miR-130b in HCC remains controversial. Here, we demonstrate that miR-130b is highly expressed in HCC and that it correlates with tumor number, vascular invasion, and TNM stage-important predictors of postoperative recurrence and metastases. Moreover, high levels of miR-130b predicted poor overall and disease-free survival of HCC patients, and in vitro and in vivo research revealed that knockdown or overexpression of miR-130b inhibited and promoted proliferation and metastasis of HCC cells, respectively. We identified PTEN as a direct functional target of miR-130b using miRNA databases and a dual luciferase report assay. Next, using a gain and loss assay and epithelial-mesenchymal transition (EMT) relative assays, we show that miR-130b may promote proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling. Collectively, our data suggests that miR-130b may have prognostic value in HCC. Additionally, the miR-130b/PTEN/p-AKT/HIF-1α axis identified in this study provides novel insight into the mechanisms of HCC metastasis, which may facilitate the development of new therapeutics against HCC.

MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying HCC progression are still not completely clear. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of a metastasis-associated miRNA named miR-188-5p in HCC. METHODS: miRNA array analysis was performed to search for metastasis-associated miRNAs in HCC. miR-188-5p expressions in tumor tissues and adjacent non-tumorous liver tissues of HCC patients and cell lines were evaluated by real-time PCR. The protein expression levels were analyzed by Western blot and immunohistochemistry. Luciferase reporter assays was used to validate the target of miR-188-5p. The effect of miR-188-5p on HCC progression was studied in vitro and in vivo. RESULTS: miR-188-5p was significantly decreased in HCC and its expression levels were highly correlated with multiple nodules, microvascular invasion, overall and disease-free survival of HCC. Ectopic expression of miR-188-5p suppressed HCC cell proliferation and metastasis in vitro and in vivo. Fibroblast growth factor 5 (FGF5) was identified as a major target of miR-188-5p. Enforced expression of miR-188-5p inhibited the expression of FGF5 significantly and the restoration of FGF5 expression reversed the inhibitory effects of miR-188-5p on HCC cell proliferation and metastasis. CONCLUSIONS: These findings collectively demonstrate a tumor suppressor role of miR-188-5p in HCC progression via targeting FGF5, suggesting that miR-188-5p could serve as a potential prognostic biomarker and therapeutic target for HCC.

MicroRNA-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting PH domain and leucine-rich repeat protein phosphatase.

UNLABELLED: Hepatocellular carcinoma (HCC) is a highly invasive tumor with frequent intrahepatic or pulmonary metastasis, which is the main reason for high recurrence and poor survival of HCC after liver resection. However, the mechanisms for metastasis remain incompletely clear. Given that microRNAs (miRNAs) are implicated in HCC progression, we explored a potential role of miRNAs in metastasis by performing miRNA expression profiling in three subtypes of HCC with different metastatic potentials. We discovered miR-331-3p as one of most significantly overexpressed miRNAs and highly associated with metastasis of HCC. Increased expression of miR-331-3p was correlated with poor long-term survival of HCC. We provided both in vivo and in vitro evidence demonstrating that miR-331-3p promoted proliferation and metastasis of HCC cells. Using an integrated approach, we uncovered that PH domain and leucine-rich repeat protein phosphatase (PHLPP) was a novel target of miR-331-3p. Indeed, the miR-331-3p-mediated effects were antagonized by reexpression of PHLPP or mimicked by silencing of PHLPP. We further showed that miR-331-3p-mediated inhibition of PHLPP resulted in stimulation of protein kinase B (AKT) and subsequent epithelial mesenchymal transition (EMT). Finally, inhibition of miR-331-3p through a jetPEI-mediated delivery of anti-miR-331-3p vector resulted in marked inhibition of proliferation and metastasis of HCC in xenograft mice. CONCLUSION: miR-331-3p promotes proliferation and EMT-mediated metastasis of HCC through suppression of PHLPP-mediated dephosphorylation of AKT. Our work implicates miR-331-3p as a potential prognostic biomarker and a novel therapeutic target.

MicroRNA-140-5p suppresses tumor growth and metastasis by targeting transforming growth factor ß receptor 1 and fibroblast growth factor 9 in hepatocellular carcinoma.

UNLABELLED: By comparing the expression profiles of microRNAs (miRNAs) in different hepatocellular carcinoma (HCC) subtypes, we identified miR-140-5p as an HCC-related miRNA. We found that miR-140-5p was significantly decreased in HCC tissues and all of six liver cancer cell lines examined and its expression levels were correlated with multiple nodules, vein invasion, capsular formation, and differentiation, as well as overall and disease-free survival of HCC. We also found that miR-140-5p suppressed HCC cell proliferation and HCC metastasis. Multipathway reporter arrays suggested that miR-140-5p inhibited transforming growth factor ß (TGF-ß) and mitogen-activated protein kinase / extracellular signal-regulated kinase (MAPK/ERK) signaling. TGFB receptor 1 (TGFBR1) and fibroblast growth factor 9 (FGF9) were then characterized as the direct targets for miR-140-5p after it was found that ectopic miR-140-5p expression suppressed TGFBR1 and FGF9 expression. Silencing TGFBR1 and FGF9 by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of TGFBR1 and FGF9 attenuated the effect of miR-140-5p on HCC growth and metastasis. CONCLUSION: These data elucidated a tumor suppressor role for miR-140-5p in HCC development and progression with therapeutic potential. Our correlation studies in clinical HCC samples further suggest that miR-140-5p could be a valuable biomarker for HCC prognosis.

The Causal Effect of Gut Microbiota and Plasma Metabolome on Lung Cancer and the Heterogeneity across Subtypes: A Mendelian Randomization Study.

The causal effect and pathways of gut microbiota and plasma metabolome on lung cancer have been important topics for personalized medicine; however, the heterogeneity of lung cancer subtypes has not gained enough attention in previous studies. This study sought to employ a Mendelian randomization analysis to screen the specific gut microbiota and plasma metabolome, which may have a causal effect on lung cancer. We further extended our analysis to estimate the effects of these exposures on various pathological subtypes of lung cancer. Furthermore, a mediation analysis was performed to identify the potential pathway underlying the influence of microbiota and metabolites. Our study identified 13 taxa and 15 metabolites with a causal association with the overall risk of lung cancer. Furthermore, we found 8 taxa and 14 plasma metabolites with a causal effect on lung adenocarcinoma, 4 taxa and 10 metabolites with a causal effect on squamous cell lung carcinoma, and 7 taxa and 16 metabolites with a causal effect on SCLC. We also identified seven mediation pathways that could potentially elucidate the influence of these microbiota and metabolites on overall lung cancer or special subtypes. Our study highlighted the heterogeneity of the gut microbiome and plasma metabolome in a lung cancer subtype and elucidated the potential underlying mechanisms. This could pave the way for more personalized lung cancer prevention and treatment.

Safety and clinical efficacy of immune checkpoint inhibitors in advanced gastric cancer in the real world.

BACKGROUND: To evaluate the clinical efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer in the real world. METHODS: The retrospective analysis was conducted on the clinical records of 402 patients with advanced gastric cancer who were admitted to the Nanjing Drum Tower Hospital between December 2017 and April 2022 and who had received immunotherapy. Observation target: drug use, treatment, adverse reaction type and grade, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). RESULTS: By retrospectively analyzing the data of patients with advanced gastric cancer treated with ICIs previously admitted to our medical center, we found some clinical characteristic factors associated with the occurrence of irAEs as well as the efficacy and prognosis: the presence or absence of hypertension, whether or not to receive targeted therapies can predict the occurrence of immune-related adverse events (irAEs), and the more the presence of irAEs, the better the prognosis. These can help clinicians in clinical drug selection. CONCLUSIONS: The results of this paper show that the occurrence of irAEs is associated with patients' OS. irAEs occurrence can prolong patients' OS. irAEs occurrence may serve as a surrogate marker for ICIs.

Case report: A case of advanced gastric cancer with multiple skin metastases, with significant relief from immunotherapy.

Gastric cancer is the fifth leading cause of cancer-related mortality worldwide, with a low 5-year survival rate in advanced stages. Cutaneous metastasis is rare in gastric cancer, with only 0.8-1% incidence. We reported a rare case of female gastric cancer. The patient had undergone subtotal gastrectomy and chemotherapy 13 years ago, followed by a subsequent surgery of residual stomach, partial jejunum, and partial colon resection 11 years later. The pathological examination revealed poorly differentiated stomach adenocarcinoma, Lauren classification: diffuse type. The patient received 2 cycles of SOX chemotherapy. Two years later, cauliflower-like skin nodules, which were surgically excised, appeared on the back. The histopathological examination showed a spindle cell tumor; no specific anti-tumor treatment was administered. Six months later, the skin lesions increased in size and number, spreading to the neck, chest, and abdomen, presenting as erythematous patches with some cauliflower-like elevations. A skin biopsy of a 1cm0.5cm0.3cm lesion on the left abdomen was performed, and based on the immunohistochemistry, clinical history, and the possibility of metastatic or infiltrating adenocarcinoma, the gastrointestinal origin was highly suspected. Genetic testing was performed on the gastric recurrence and skin lesions, revealing 103 shared genetic variations, further suggesting the skin metastasis originated from gastric cancer. Subsequently, the patient received 10 cycles of immunotherapy combined with intravenous chemotherapy (200mg Tislelizumab and 100mg albumin-bound paclitaxel). The treatment response was evaluated as partial remission, with significant improvement in the skin lesions compared to before. This case highlights the possibility of tumor metastasis in patients with extensive skin lesions in advanced gastric cancer. Early examination, diagnosis, skin biopsy, immunohistochemistry, and genetic sequencing are recommended.

SIN1 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition.

BACKGROUND: Stress-activated protein kinase (SAPK) interacting protein 1 (SIN1) is essential for early embryonic development and is the key regulator of Akt, which plays an important role in various pathological conditions such as cancer. However, the biological function and clinical significance of SIN1 in hepatocellular carcinoma (HCC) remains unknown. METHODS: Real-time quantitative reverse-transcriptase polymerase chain reaction analysis, western blot analysis, and immunohistochemical staining were used to test the expression level of SIN1, and its correlation with clinicopathologic parameters as well as the prognosis for patients with HCC were analyzed. In addition, the biological function and molecular mechanisms of SIN1 in HCC were investigated. RESULTS: SIN1 levels were elevated predominantly in HCC tissues, and its level in solitary large HCC was significantly lower than those in nodular HCC (P = .016), but showed no significant differences between solitary large HCC and small HCC (P > .05). Levels of SIN1 were up-regulated in highly metastatic HCC cell lines (HCCLM3 and MHCC97-H), whereas their invasion and migration significantly decreased after depletion of SIN1. High expression of SIN1 was associated with tumor number (P = .012), capsular formation (P = .037), and venous invasion (P = .023) and was an independent risk factor for overall survival (P = .046). Finally, SIN1 was capable of promoting invasion and metastasis of HCC by facilitating epithelial-mesenchymal transition. CONCLUSIONS: The current findings suggest that SIN1 plays an important role in HCC invasion and metastasis by facilitating epithelial-mesenchymal transition.

Safety and feasibility of robotic-assisted thoracic surgery after neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

Objectives: This study aimed to evaluate the safety and feasibility of robotic-assisted thoracic surgery (RATS) after neoadjuvant chemoimmunotherapy in NSCLC. Methods: We retrospectively collected data for NSCLC patients who received thoracic surgery after neoadjuvant chemoimmunotherapy from May 2020 to August 2022. Surgery details, pathological response, and perioperative outcome were compared between video-assisted thoracic surgery (VATS) group and RATS group. Inverse probability of treatment weighting (IPTW) was used to equal the baseline characteristics. Results: A total of 220 patients were divided into 78 VATS patients and 142 RATS patients. There was no 90-day mortality in either group. RATS patients demonstrated better results in conversion rate to thoracotomy (VATS vs. RATS: 28.2% vs. 7.5%, P < 0.001), number of lymph node stations harvested (5.63 ± 1.75 vs. 8.09 ± 5.73, P < 0.001), number of lymph nodes harvested (13.49 ± 9.325 vs. 20.35 ± 10.322, P < 0.001), yield pathologic-N (yp-N) assessment (yp-N0, 88.5% vs. 67.6%; yp-N1, 7.6% vs. 12.6%; yp-N2, 3.8% vs. 19.7%; P < 0.001), and visual analog scale pain score after surgery (4.41 ± 0.93 vs. 3.77 ± 1.21, P=0.002). However, there were no significant differences in pathological response evaluation for neoadjuvant chemoimmunotherapy (P = 0.493) and complication rate (P = 0.803). After IPTW-adjustment, these results remained constant. Conclusions: RATS reduced the risk of conversion to thoracotomy, provided a better yp-N stage evaluation, and improved pain score; this suggests that RATS is safe and feasible for NSCLC patients after neoadjuvant chemoimmunotherapy.

Prognostic significance of tumor-associated macrophages polarization markers in lung cancer: a pooled analysis of 5105 patients.

BACKGROUND: The prognostic significance of tumor-associated macrophages (TAMs) in patients with lung cancer (LCa) remains controversial. We therefore conducted the present study to systematically evaluate the role of different TAMs markers and histologic locations on the prognosis of LCa. METHODS: Searches of Web of Science, PubMed, and EMBASE databases were performed up to 28 February 2022. The pooled analysis was conducted in random-effect or fixed-effects model with hazard risk (HR) and 95% confidence interval (CI) for survival data including overall survival (OS), and disease-free survival (DFS) from raw or adjusted measures, according to different TAMs markers and histologic locations. RESULTS: Including a total of 5105 patients from 30 eligible studies, the results indicated that the total count of CD68+ TAMs was negatively associated with OS and DFS, which was also observed in the relationship of CD68+ or CD204+ TAMs in tumor stroma (TS) with OS and DFS (all P<0.05). Conversely, higher CD68+ TAMs density in tumor nest (TN) or TN/TS ratio of CD68+ TAMs predicted better OS (all P<0.05). Similarly, higher HLA-DR+ TAMs density was correlated with better OS in TN and TS (all P<0.05). Besides, neither nest CD163+ TAM density nor stromal CD163+ TAM density was a prognostic factor in LCa patients (all P>0.05). CONCLUSION: Our study indicated that different TAMs markers and histologic locations could bring about different prognostic effects in LCa patients. Great understanding of the infiltration modes of TAMs may contribute to improve outcomes of LCa patients.

Bioinformatics construction and experimental validation of a cuproptosis-related lncRNA prognostic model in lung adenocarcinoma for immunotherapy response prediction.

Cuproptosis is a newly form of cell death. Cuproptosis related lncRNA in lung adenocarcinoma (LUAD) has also not been fully elucidated. In the present study, we aimed to construct a prognostic signature based on cuproptosis-related lncRNA in LUAD and investigate its association with immunotherapy response. The RNA-sequencing data, clinical information and simple nucleotide variation of LUAD patients were obtained from TCGA database. The LASSO Cox regression was used to construct a prognostic signature. The CIBERSORT, ESTIMATE and ssGSEA algorithms were applied to assess the association between risk score and TME. TIDE score was applied to reflect the efficiency of immunotherapy response. The influence of overexpression of lncRNA TMPO-AS1 on A549 cell was also assessed by in vitro experiments. The lncRNA prognostic signature included AL606834.1, AL138778.1, AP000302.1, AC007384.1, AL161431.1, TMPO-AS1 and KIAA1671-AS1. Low-risk group exhibited much higher immune score, stromal score and ESTIMATE score, but lower tumor purity compared with high-risk groups. Also, low-risk group was associated with a much higher score of immune cells and immune related function sets, indicating an immune activation state. Low-risk patients had relative higher TIDE score and lower TMB. External validation using IMvigor210 immunotherapy cohort demonstrated that low-risk group had a better prognosis and might more easily benefit from immunotherapy. Overexpression of lncRNA TMPO-AS1 promoted the proliferation, migration and invasion of A549 cell line. The novel cuproptosis-related lncRNA signature could predict the prognosis of LUAD patients, and helped clinicians stratify patients appropriate for immunotherapy and determine individual therapeutic strategies.

Cuproptosis Depicts Immunophenotype and Predicts Immunotherapy Response in Lung Adenocarcinoma.

BACKGROUND: Although significant progress has been made in immunotherapy for lung adenocarcinoma (LUAD), there is an urgent need to identify effective indicators to screen patients who are suitable for immunotherapy. Systematically investigating the cuproptosis-related genes (CRGs) in LUAD may provide new ideas for patients' immunotherapy stratification. METHOD: We comprehensively analyzed the landscape of 12 CRGs in a merged TCGA and GEO LUAD cohort. We investigated the associations between tumor microenvironment and immunophenotypes. We utilized a risk score to predict the prognosis and immunotherapy response for an individual patient. Additionally, we conducted CCK-8 experiments to evaluate the impact of DLGAP5 knockdown on A549 cell proliferation. RESULT: We utilized an integrative approach to analyze 12 CRGs and differentially expressed genes (DEGs) in LUAD samples, resulting in the identification of two distinct CRG clusters and two gene clusters. Based on these clusters, we generated immunophenotypes and observed that the inflamed phenotype had the most abundant immune infiltrations, while the desert phenotype showed the poorest immune infiltrations. We then developed a risk score model for individual patient prognosis and immunotherapy response prediction. Patients in the low-risk group had higher immune scores and ESTIMATE scores, indicating an active immune state with richer immune cell infiltrations and higher expression of immune checkpoint genes. Moreover, the low-risk group exhibited better immunotherapy response according to IPS, TIDE scores, and Imvigor210 cohort validation results. In addition, our in vitro wet experiments demonstrated that DLGAP5 knockdown could suppress the cell proliferation of A549. CONCLUSION: Novel cuproptosis molecular patterns reflected the distinct immunophenotypes in LUAD patients. The risk model might pave the way to stratify patients suitable for immunotherapy and predict immunotherapy response.

A PD-L1 targeting nanotheranostic for effective photoacoustic imaging guided photothermal-immunotherapy of tumor.

Tumor immunotherapy has been partly effective for specific cancers. However, problems such as low immune response, limited antitumor effectiveness, and high antibody costs still persist. Synergistic therapeutic approaches, such as immune checkpoint inhibition in conjunction with photothermal therapy and photoacoustic imaging, are expected to provide approaches for more precise and efficient immunotherapy of tumors. Furthermore, developing alternatives for antibodies, such as PD-L1 aptamers and nanocarriers, would reduce the cost of tumor immunotherapy. Herein, we develop a PD-L1-targeting nanotheranostic to block immune checkpoints for synergistic photothermal-immunotherapy against tumors, along with effective photoacoustic (PA) imaging. The nanotheranostic is synthesized by the modification of gold nanorods (GNRs) with the PD-L1 aptamer (APDL1), which can sensitively and specifically recognize PD-L1 on the tumor cell surface, and mediate nanoparticle accumulation and strong PA signals in tumors. The aptamer is released from GNR through a competition of glutathione (GSH) and is then functionalized as a PD-L1 blockade. In collaboration with the concurrent photothermal therapy, antitumor immunity is significantly augmented by enhancing the filtration of matured dendritic cells and suppressing regulatory T cells, followed by the activation of cytotoxic T cells and inhibition of T cell exhaustion. Such a nanotheranostic modality effectively suppresses tumor growth in mice, representing an appealing platform for both biological imaging and photoimmunotherapy of tumors.