Xylan-directed cell wall assembly in grasses.

Xylan is the most abundant hemicellulosic polysaccharide in the cell walls of grasses and is pivotal for the assembly of distinct cell wall structures that govern various cellular functions. Xylan also plays a crucial role in regulating biomass recalcitrance, ultimately affecting the utilization potential of lignocellulosic materials. Over the past decades, our understanding of the xylan biosynthetic machinery and cell wall organization has substantially improved due to the innovative application of multiple state-of-the-art techniques. Notably, novel xylan-based nanostructures have been revealed in the cell walls of xylem vessels, promoting a more extensive exploration of the role of xylan in the formation of cell wall structures. This Update summarizes recent achievements in understanding xylan biosynthesis, modification, modeling, and compartmentalization in grasses, providing a brief overview of cell wall assembly regarding xylan. We also discuss the potential for tailoring xylan to facilitate the breeding of elite energy and feed crops.

The molecular characteristics could supplement the staging system of pT2/T3N0M0 esophageal squamous cell carcinoma: a translational study based on a cohort with over 20 years of follow-up.

OBJECTIVE: This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. METHODS: The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). RESULTS: A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients' prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001). CONCLUSIONS: Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone.

Comparison of Short-Term Outcomes Between Robot-Assisted and Video-Assisted Segmentectomy for Small Pulmonary Nodules: A Propensity Score-Matching Study.

BACKGROUND: Our study aimed to compare the short-term outcomes between robot-assisted segmentectomy (RAS) and video-assisted segmentectomy (VAS) for small pulmonary nodules. METHODS: The study included of 299 segmentectomies (132 RAS and 167 VAS procedures) for small pulmonary nodules between June 2018 and November 2021. The patients were divided into two groups: the RAS group and the VAS group. Propensity score-matching (PSM) analysis was performed to minimize bias. A logistic regression model was performed to identify the independent risk factors associated with complications. RESULTS: Before PSM, the following clinical variables were not balanced: age (P = 0.004), tumor size (P < 0.001), forced expiratory volume for 1 s (FEV1), and FEV1 percentage (P < 0.001). The patients with RAS had a shorter operative time (P = 0.014), less blood loss, a shorter postoperative hospital stay, less use of strong opioids, less drainage on postoperative day 1, and less postoperative total drainage, but more cost (all P < 0.001). Conversion to open surgery was performed for two patients in the VAS group but none in the RAS group. After PSM, 53 pairs were successfully matched. The data again suggested that the patients with RAS had less blood loss, a shorter postoperative hospital stay, and less use of strong opioids, but more cost (all P < 0.001). The operation time also was shorter in the RAS group, with a borderline statistically significant P value (0.053). CONCLUSIONS: In our study, RAS had better short-term outcomes than VAS, indicating a safer and more efficient technique than VAS.

Reconsidering N component of cancer staging for T1-2N0-2M0 small-cell lung cancer: a retrospective study based on multicenter cohort.

BACKGROUND: The current nodal (pN) classification still has limitations in stratifying the prognosis of small cell lung cancer (SCLC) patients with pathological classifications T1-2N0-2M0. Thus. This study aimed to develop and validate a modified nodal classification based on a multicenter cohort. MATERIALS AND METHODS: We collected 1156 SCLC patients with pathological classifications T1-2N0-2M0 from the Surveillance, Epidemiology, and End Results database and a multicenter database in China. The X-tile software was conducted to determine the optimal cutoff points of the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). The Kaplan-Meier method, the Log-rank test, and the Cox regression method were used in this study. We classified patients into three pathological N modification categories, new pN#1 (pN0-#ELNs > 3), new pN#2 (pN0-#ELNs ≤ 3 or pN1-2-#LNR ≤ 0.14), and new pN#3 (N1-2-#LNR > 0.14). The Akaike information criterion (AIC), Bayesian Information Criterion, and Concordance index (C-index) were used to compare the prognostic, predictive ability between the current pN classification and the new pN component. RESULTS: The new pN classification had a satisfactory effect on survival curves (Log-rank P < 0.001). After adjusting for other confounders, the new pN classification could be an independent prognostic indicator. Besides, the new pN component had a much more accurate predictive ability in the prognostic assessment for SCLC patients of pathological classifications T1-2N0-2M0 compared with the current pN classification in the SEER database (AIC: 4705.544 vs. 4731.775; C-index: 0.654 vs. 0.617, P < 0.001). Those results were validated in the MCDB from China. CONCLUSIONS: The multicenter cohort developed and validated a modified nodal classification for SCLC patients with pathological category T1-2N0-2M0 after surgery. Besides, we propose that an adequate lymph node dissection is essential; surgeons should perform and consider the situation of ELNs and LNR when they evaluate postoperative prognoses of SCLC patients.

Heterogeneity and Clinical Effect of Epidermal Growth Factor Receptor in Primary Lung and Brain Metastases of Nonsmall Cell Lung Cancer.

INTRODUCTION: This study aimed to analyze the heterogeneity in epidermal growth factor receptor (EGFR) gene mutation and its impact on clinical outcomes in primary tumor and corresponding brain metastasis (BM) in nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Primary pulmonary tumors and paired BMs of 27 NSCLC patients were surgically removed. All brain lesions were histologically confirmed as metastatic NSCLC. EGFR gene mutation status was detected by using amplification refraction mutation system. McNemar test was performed to compare EGFR mutation status between lung primary tumors and metastatic brain tumors and Kappa test was performed to quantify the agreement between the two. RESULTS: Of the 27 patients, nine cases were found to have EGFR mutations in BMs and 10 had a positive EGFR mutation status in primary lung tumor tissue. The rate of consistency of the matched tumor was 24/27 (88.9%). Among the three cases presenting EGFR mutational heterogeneity, two patients harbored an EGFR mutation in the primary tumor but not in the BMs; meanwhile, the last patient demonstrated the opposite pattern. Compared to patients with consistent EGFR mutations, patients with inconsistent mutations showed better outcomes. Further analysis revealed that the two patients whose EGFR mutant-type primary tumor progressed to wild-type cerebral metastatic tumor had longer overall survival than the patient whose EGFR wild-type primary tumor progressed to mutant-type brain metastatic tumor. CONCLUSIONS: Heterogeneity of EGFR mutation status was observed between primary NSCLC and paired BM. Patients possessing a wild-type EGFR mutation in BM might have better outcomes, especially those with transition from mutant to wild-type.

Effect of low-intensity pulsed ultrasound combined with Rhodiola rosea on proliferation and differentiation of osteoblasts.

Osteoblasts (OB), as the mesenchymal progenitor cells differentiated from the inner and outer periosteum and the stroma in bone marrow, can specifically secrete a variety of bioactive substances, thereby regulating and influencing the process of bone formation and reconstruction. Therefore, promoting the proliferation and differentiation of OB plays an important role in promoting bone formation. Based on this, this study studied the proliferation and differentiation of OB by low-intensity pulsed ultrasound (LIPUS) combined with Rhodiola rosea to provide a reliable theoretical basis for bone repair. In this study, rat OB was used as the research material and divided into groups A, B, C and D according to different intervention methods after osteogenic culture. Joint Salvia miltiorrhiza LIPUS ever seen from the results of the study promotes the strongest OB proliferation, at the same time, effectively reduces the apoptosis rate of the OB and apoptosis-related proteins expression, and promotes the OCN and ALO protein expression, indicated by LIPUS Salvia miltiorrhiza can effectively promote the osteoblast proliferation, differentiation, in order to promote cartilage repair and bone strengthen provides an effective means.

Diterpenoids with an unusual tricyclo[10.3.0.02,9]pentadecane skeleton from Pedilanthus tithymaloides as multidrug resistance modulators.

Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.

Arabinosyl Deacetylase Modulates the Arabinoxylan Acetylation Profile and Secondary Wall Formation.

Acetylation, a prevalent modification of cell-wall polymers, is a tightly controlled regulatory process that orchestrates plant growth and environmental adaptation. However, due to limited characterization of the enzymes involved, it is unclear how plants establish and dynamically regulate the acetylation pattern in response to growth requirements. In this study, we identified a rice (Oryza sativa) GDSL esterase that deacetylates the side chain of the major rice hemicellulose, arabinoxylan. Acetyl esterases involved in arabinoxylan modification were screened using enzymatic assays combined with mass spectrometry analysis. One candidate, DEACETYLASE ON ARABINOSYL SIDECHAIN OF XYLAN1 (DARX1), is specific for arabinosyl residues. Disruption of DARX1 via Tos17 insertion and CRISPR/Cas9 approaches resulted in the accumulation of acetates on the xylan arabinosyl side chains. Recombinant DARX1 abolished the excess acetyl groups on arabinoxylan-derived oligosaccharides of the darx1 mutants in vitro. Moreover, DARX1 is localized to the Golgi apparatus. Two-dimensional 13C-13C correlation spectroscopy and atomic force microscopy further revealed that the abnormal acetylation pattern observed in darx1 interrupts arabinoxylan conformation and cellulose microfibril orientation, resulting in compromised secondary wall patterning and reduced mechanical strength. This study provides insight into the mechanism controlling the acetylation pattern on arabinoxylan side chains and suggests a strategy to breed robust elite crops.

Postoperative survival effect of the number of examined lymph nodes on esophageal squamous cell carcinoma with pathological stage T1-3N0M0.

BACKGROUND: The postoperative survival effect of the number of examined lymph nodes on patients of R0-resected esophageal squamous cell carcinoma with pathological stage T1-3N0M0 is still unclear. METHODS: Patients diagnosed with pathological stage T1-3N0M0 esophageal squamous cell carcinoma from two cancer databases-our cancer center (N = 707), and Surveillance Epidemiology and End Results (N = 151). The primary clinical endpoint was overall survival. The X-tile software was used to determine the optimal cutoff value of the number of examined lymph nodes, and propensity score matching was conducted to reduce selection bias according to the results of X-tile software. The cohort of 151 patients from another database was used for validation. RESULTS: X-tile software provided an optimal cutoff value of 15 examined lymph nodes based on 707 patients, and 231 pairs of matched patients were included. In the unmatched cohort, Cox proportional hazard regression analysis revealed better overall survival in patients with more than 15 examined lymph nodes (adjusted hazard ratio, 0.566, 95% confidence interval, 0.445-0.720; p < 0.001) compared with patients with 15 or fewer examined lymph nodes. In the validation cohort, patients with more than 15 examined lymph nodes also had better overall survival (adjusted hazard ratio 0.665, p = 0.047). CONCLUSIONS: The number of examined lymph nodes is a significant prognostic factor in esophageal squamous cell carcinoma patients with pathological stage T1-3N0M0, and more than 15 examined lymph nodes are associated with better overall survival. Although the difference is not significant, the survival curve of patients with examined lymph nodes > 30 is better than those with examined lymph nodes 15-30. We believe that the number of examined lymph nodes can provide prognostic guidance for those patients, and the more examined lymph nodes cause lesser occult lymph nodes metastasis and lead to a better prognosis. Therefore, surgeons and pathologists should try to examine as many lymph nodes as possible to evaluate the pathological stage precisely. However, we need more validation from other studies.

Improving the accuracy of prognosis for clinical stage I solid lung adenocarcinoma by radiomics models covering tumor per se and peritumoral changes on CT.

OBJECTIVES: To assess methods to improve the accuracy of prognosis for clinical stage I solid lung adenocarcinoma using radiomics based on different volumes of interests (VOIs). METHODS: This retrospective study included patients with postoperative clinical stage I solid lung adenocarcinoma from two hospitals, center 1 and center 2. Three databases were generated: dataset A (training set from center 1), dataset B (internal test set from center 1), and dataset C (external validation test from center 2). Disease-free survival (DFS) data were collected. CT radiomics models were constructed based on four VOIs: gross tumor volume (GTV), 3 mm external to the tumor border (peritumoral volume [PTV]0~+3), 6 mm crossing tumor border (PTV-3~+3), and 6 mm external to the tumor border (PTV0~+6). The area under the receiver operating characteristic curve (AUC) was used to compare the model accuracies. RESULTS: A total of 334 patients were included (204 and 130 from centers 1 and 2). The model using PTV-3~+3 (AUC 0.81 [95% confidence interval {CI}: 0.75, 0.94], 0.81 [0.63, 0.90] for datasets B and C) outperformed the other three models, GTV (0.73 [0.58, 0.81], 0.73 [0.58, 0.83]), PTV0~+3 (0.76 [0.52, 0.87], 0.75 [0.60, 0.83]), and PTV0~+6 (0.72 [0.60, 0.81], 0.69 [0.59, 0.81]), in datasets B and C, all p < 0.05. CONCLUSIONS: A radiomics model based on a VOI of 6 mm crossing tumor border more accurately predicts prognosis of clinical stage I solid lung adenocarcinoma than that based on VOIs including overall tumor or external rims of 3 mm and 6 mm. KEY POINTS: • Radiomics is a useful approach to improve the accuracy of prognosis for stage I solid adenocarcinoma. • The radiomics model based on VOIs that includes 3 mm within and external to the tumor border (peritumoral volume [PTV]-3~+3) outperformed models that included either only the tumor itself or those that only included the peritumoral volume.

The role of vascular invasion and lymphatic invasion in predicting recurrent thoracic oesophageal squamous cell carcinoma.

BACKGROUND: Numerous studies have addressed lymphovascular invasion (LVI) in patients with thoracic oesophageal squamous cell carcinoma (ESCC); however, little is known about the individual roles of lymphatic invasion (LI) and vascular invasion (VI). We aimed to analyse the prognostic significance of LI and VI in patients with thoracic ESCC from a single centre. METHODS: This retrospective study included 396 patients with thoracic ESCC who underwent oesophagectomy and lymphadenectomy in our hospital. The relationship between LI, VI and the other clinical features was analysed, and disease-free survival (DFS) was calculated. Survival analysis was performed by univariate and multivariate statistics. RESULTS: Briefly, VI and LI were present in 25.8% (102 of 396) and 23.7% (94 of 396) of ESCC patients, respectively, with 9.15% patients presenting both LI and VI; the remaining patients did not present LI or VI. We found that LI was significantly associated with pN stage (P<0.001) and pTNM stage (P<0.001), and similar results were found in VI. Moreover, survival analysis showed that pT stage (P<0.001), pN stage (P=0.001), pTNM stage (p<0.001), VI (P=0.001) and LI (P<0.001) were associated with DFS in ESCC. Furthermore, multivariate analysis suggested that pT stage (RR=1.4, P =0.032), pN stage (RR=1.9, P<0.001) and LI (RR=1.5, P=0.008) were independent predictive factors for DFS. Finally, relapse was observed in 110 patients (lymph node metastasis, 78 and distant, 32) and 147 patients with cancer-related deaths. Subanalysis showed that LI-positive patients had higher lymph node metastasis, although there was no significant difference (32.1% vs. 15.6%, P=0.100). CONCLUSIONS: LI and VI were common in ESCC; they were all survival predictors for patients with ESCC, and LI was independent. Patients with positive LI were more likely to suffer lymph node metastasis.

A prognostic model for stratification of stage IB/IIA esophageal squamous cell carcinoma: a retrospective study.

BACKGROUND: To explore the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients with stage IB/IIA, using a prognostic score (PS). METHODS: Stage IB/IIA ESCC patients who underwent esophagectomy from 1999 to 2010 were included. We retrospectively recruited 153 patients and extracted their medical records. Moreover, we analyzed the programmed death ligand-1 (PD-L1) expression of their paraffin tissue. The cohort were randomly divided into a training group (N = 123) and a validation group (N = 30). We selected overall survival (OS) as observed endpoint. Prognostic factors with a multivariable two-sided P < 0.05 met standard of covariate inclusion. RESULTS: Univariable and multivariable analyses identified pTNM stage, the number of lymph nodes (NLNs) and PD-L1 expression as independent OS predictors. Primary prognostic score which comprised above three covariates adversely related with OS in two cohorts. PS discrimination of OS was comparable between the training and internal validation cohorts (C-index = 0.774 and 0.801, respectively). In addition, the PS system had an advantage over pTNM stage in the identification of high-risk patients (C-index = 0.774 vs. C-index = 0.570, P < 0.001). Based on PS cutoff, training and validation datasets generated low-risk and high-risk groups with different OS. Our three-factor PS predicted OS (low-risk subgroup vs. high-risk subgroup 60-month OS, 74% vs. 23% for training cohort and 83% vs. 45% for validation cohort). CONCLUSION: Our study suggested a PS for significant clinical stratification of IB/IIA ESCC to screen out subgroups with poor prognosis.

The plant cell wall: Biosynthesis, construction, and functions.

The plant cell wall is composed of multiple biopolymers, representing one of the most complex structural networks in nature. Hundreds of genes are involved in building such a natural masterpiece. However, the plant cell wall is the least understood cellular structure in plants. Due to great progress in plant functional genomics, many achievements have been made in uncovering cell wall biosynthesis, assembly, and architecture, as well as cell wall regulation and signaling. Such information has significantly advanced our understanding of the roles of the cell wall in many biological and physiological processes and has enhanced our utilization of cell wall materials. The use of cutting-edge technologies such as single-molecule imaging, nuclear magnetic resonance spectroscopy, and atomic force microscopy has provided much insight into the plant cell wall as an intricate nanoscale network, opening up unprecedented possibilities for cell wall research. In this review, we summarize the major advances made in understanding the cell wall in this era of functional genomics, including the latest findings on the biosynthesis, construction, and functions of the cell wall.

Identification of a 4-lncRNA signature predicting prognosis of patients with non-small cell lung cancer: a multicenter study in China.

BACKGROUND: Previous findings have indicated that the tumor, nodes, and metastases (TNM) staging system is not sufficient to accurately predict survival outcomes in patients with non-small lung carcinoma (NSCLC). Thus, this study aims to identify a long non-coding RNA (lncRNA) signature for predicting survival in patients with NSCLC and to provide additional prognostic information to TNM staging system. METHODS: Patients with NSCLC were recruited from a hospital and divided into a discovery cohort (n = 194) and validation cohort (n = 172), and detected using a custom lncRNA microarray. Another 73 NSCLC cases obtained from a different hospital (an independent validation cohort) were examined with qRT-PCR. Differentially expressed lncRNAs were determined with the Significance Analysis of Microarrays program, from which lncRNAs associated with survival were identified using Cox regression in the discovery cohort. These prognostic lncRNAs were employed to construct a prognostic signature with a risk-score method. Then, the utility of the prognostic signature was confirmed using the validation cohort and the independent cohort. RESULTS: In the discovery cohort, we identified 305 lncRNAs that were differentially expressed between the NSCLC tissues and matched, adjacent normal lung tissues, of which 15 are associated with survival; a 4-lncRNA prognostic signature was identified from the 15 survival lncRNAs, which was significantly correlated with survivals of NSCLC patients. This signature was further validated in the validation cohort and independent validation cohort. Moreover, multivariate Cox analysis demonstrates that the 4-lncRNA signature is an independent survival predictor. Then we established a new risk-score model by combining 4-lncRNA signature and TNM staging stage. The receiver operating characteristics (ROC) curve indicates that the prognostic value of the combined model is significantly higher than that of the TNM stage alone, in all the cohorts. CONCLUSIONS: In this study, we identified a 4-lncRNA signature that may be a powerful prognosis biomarker and can provide additional survival information to the TNM staging system.

Rice Homeobox Protein KNAT7 Integrates the Pathways Regulating Cell Expansion and Wall Stiffness.

During growth, plant cells must coordinate cell expansion and cell wall reinforcement by integrating distinct regulatory pathways in concert with intrinsic and external cues. However, the mechanism underpinning this integration is unclear, as few of the regulators that orchestrate cell expansion and wall strengthening have been identified. Here, we report a rice (Oryza sativa) Class II KNOX-like homeobox protein, KNOTTED ARABIDOPSIS THALIANA7 (KNAT7), that interacts with different partners to govern cell expansion and wall thickening. A loss-of-function mutation in KNAT7 enhanced wall mechanical strength and cell expansion, resulting in improved lodging resistance and grain size. Overexpression of KNAT7 gave rise to the opposite phenotypes, with plants having weaker cell walls and smaller grains. Biochemical and gene expression analyses revealed that rice KNAT7 interacts with a secondary wall key regulator, NAC31, and a cell growth master regulator, Growth-Regulating Factor 4 (GRF4). The KNAT7-NAC31 and KNAT7-GRF4 modules suppressed regulatory pathways of cell expansion and wall reinforcement, as we show in internode and panicle development. These modules function in sclerenchyma fiber cells and modulate fiber cell length and wall thickness. Hence, our study uncovers a mechanism for the combined control of cell size and wall strengthening, providing a tool to improve lodging resistance and yield in rice production.

Polyphyllosides A-F, six new spirostanol saponins from the stems and leaves of Paris polyphylla var. chinensis.

The first phytochemical investigation on the steroidal saponins from the stems and leaves of Paris polyohylla var. chinensis led to the discovery and characterization of six new spirostanol saponins, named polyphyllosides A-F (1-6), along with four known analogues (7-10). Their structures were unambiguously established via extensive spectroscopic data and chemical methods. Both polyphyllosides A and B had a rare aglycone with a C-4/C-5 double bond and a C-6 hydroxy group moiety, whereas polyphylloside C represents the first saponin with a unique aglycone sharing a C-6/C-7 double bond and a C-5 hydroxy group unit. All these saponins were evaluated for their cytotoxic activities against five selected human cancer cell lines. Among these, the known saponins 7 and 10 exhibited significant cytotoxic effects on HeLa cells with IC50 values of 4.16 and 4.45 µM, respectively. The structure-activity relationships (SAR) of these isolates were also discussed. Flow cytometric analysis indicated that 7 could induce MDA-MB-231 cell death in a concentration-dependent manner. Saponin 7 was proved to affect the cell cycle distribution and induced G2/M phase arrest in MDA-MB-231 cells.

Association between number of dissected lymph nodes and survival in stage IA non-small cell lung cancer: a propensity score matching analysis.

BACKGROUND: For patients with stage IA non-small cell lung cancer (NSCLC) with tumor size ≤ 2 cm, the prognostic significance of the number of removed lymph nodes (NLNs) through different surgical methods remains unclear. To determine the association of NLNs with cancer-specific survival (CSS) and overall survival (OS) in patients with stage IA NSCLC with tumor size ≤ 2 cm who underwent different lung surgeries. METHODS: We retrospectively enrolled 7293 patients from the Surveillance, Epidemiology and End Results database. Median NLNs was used to classify the patients into two groups: group A with NLNs ≤ 5 and group B with NLNs > 5. Propensity score matching (PSM) was performed to decrease selection bias. Kaplan-Meier analysis and Cox regression analysis were performed to identify the association between NLNs and survival outcomes. RESULTS: Group B had better survival than group A in the unmatched cohort and matched cohort (all P < 0.05). Multivariable analyses revealed that the NLNs significantly affected CSS and OS of eligible cases in the unmatched cohort and matched cohort. Additionally, we found that the NLNs was a protective prognostic predictor of OS for patients who underwent wedge resection, segmental resection, or lobectomy. CONCLUSION: The NLNs was a protective prognostic factor in NSCLC patients with tumor size ≤ 2 cm. We demonstrated that patients with > 5 NLNs in the cohort of wedge resection, segmental resection, or lobectomy exhibited a significantly better OS.

Intratumor heterogeneity comparison among different subtypes of non-small-cell lung cancer through multi-region tissue and matched ctDNA sequencing.

Understanding of intratumor heterogeneity (ITH) among different non-small cell lung cancer (NSCLC) subtypes is necessary. Whether circulating tumor DNA (ctDNA) profile could represent these ITH is still an open question. We performed 181 multi-region tumor tissues sequencing and matched ctDNA sequencing from 32 operative NSCLC to compare ITH among different NSCLC subtypes, including EGFR-mutant lung adenocarcinoma (LUAD), KRAS-mutant LUAD, EGFR&KRAS-wild-type LUAD, and lung squamous cell carcinoma (LUSC), and examine potential value of ctDNA for ITH analysis. ITH is evaluated by ITH index (ITHi). If the somatic genetic alteration is shared by all the tissue regions, it is defined as trunk mutation. Otherwise, it is called branch mutation. The ITHi will be higher, if the tumor has less trunk mutations. We found EGFR-mutant LUAD showed significantly higher ITHi than KRAS-mutant LUAD/wild-type LUAD (P = 0.03) and numerically higher ITH than LUSC. For trunk mutations, driver mutations were identified at a higher proportion than passenger mutations (60% vs. 40%, P = 0.0023) in overall, especially in EGFR-mutant LUAD (86% vs. 14%, P = 0.0004), while it was opposite in KRAS-mutant LUAD (40% vs. 60%, P = 0.18). For branch mutations, the proportions of driver mutations and passenger mutations were similar for each NSCLC subtype. ctDNA analysis showed unsatisfactory detections of tumor-derived trunk and branch mutations (43% vs. 23%, P = 4.53e-6) among all NSCLC subtypes. In summary, EGFR-mutant LUAD has the highest ITH than other NSCLC subtypes, offering further understanding of tumorigenesis mechanisms among different NSCLC subtypes. Besides, ctDNA maybe not an appropriate method to reflect ITH.

Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis.

The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets.

A Model Shows Utility in Predicting Postoperative Recurrence and Distant Metastasis in Curatively Resected Esophageal Squamous Cell Cancer.

After curative treatment of esophageal squamous cell cancer (ESCC), patients are at high risk for recurrence. The objective of this study was to develop an index with a high sensitivity and specificity to predict ESCC patients' recurrence and prognosis. A retrospective analysis was conducted on consecutive patients with EC who underwent esophagectomy. In total, 1417 patients were included in the current investigation. In total, 770 patients were included in the current study's exploratory group. Alcohol consumption, TNM classification, number of lymph node station metastases, and number of lymph node metastases were significantly correlated with recurrence. Multivariate logistical regression analysis resulted in the development of an equation for predicting recurrence and prognosis (REEC). When using the REEC value to predict recurrence, the cutoff value was 1.095, the area under the curve (AUC) values of the REEC were 0.68 ( p < 0.001) in the Exploratory Group and 0.65 ( p < 0.001) in the Validation Group, and the sensitivity and specificity were 76.68% and 51.18%, respectively. When using the REEC value to predict prognosis, the cutoff value was 1.215, the AUC values of the REEC were 0.65 ( p < 0.001) in the Exploratory Group and 0.64 ( p < 0.001) in the Validation Group, and the sensitivity and specificity were 73.12% and 50.67%, respectively. In the Exploratory Group, when the REEC value was >1.095, patients had a longer median overall survival (OS) and median disease-free survival (DFS) than those whose REEC value was < 1.095 (70.01±2.01 months versus 50.92±2.85 months and 75.66±1.35 months versus 53.68±2.81 months, respectively, p < 0.001). The differences were confirmed to still exist in the Validation Group (48.12±1.47 vs 32.68±2.53 months and 55.61±1.32 vs 35.68±2.73 months respectively, p < 0.001).This study reported an index that can predict esophageal cancer recurrence and prognosis, and its use can benefit patients.