Development and validation of an endoplasmic reticulum stress long non-coding RNA signature for the prognosis and immune landscape prediction of patients with lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD), the most common histotype of lung cancer, may have variable prognosis due to molecular variations. This work investigated long non-coding RNA (lncRNA) related to endoplasmic reticulum stress (ERS) to predict the prognosis and immune landscape for LUAD patients. Methods: RNA data and clinical data from 497 LUAD patients were collected in the Cancer Genome Atlas database. Pearson correlation analysis, univariate Cox regression, least absolute shrinkage and selection operator regression analyses, as well as the Kaplan-Meier method, were used to screen for ERS-related lncRNAs associated with prognosis. The risk score model was developed using multivariate Cox analysis to separate patients into high- and low-risk groups and a nomogram was constructed and evaluated. Finally, we explore the potential functions and compared the immune landscapes of two groups. Quantitative real-time PCR was used to verify the expression of these lncRNAs. Results: Five ERS-related lncRNAs were shown to be strongly linked to patients' prognosis. A risk score model was built by using these lncRNAs to categorize patients based on their median risk scores. For LUAD patients, the model was found to be an independent prognostic predictor (p < 0.001). The signature and clinical variables were then used to construct a nomogram. With 3-year and 5-year OS' AUC of 0.725 and 0.740, respectively, the nomogram's prediction performance is excellent. The 5-lncRNA signature was associated with DNA replication, epithelial-mesenchymal transition, and the pathway of cell cycle, P53 signaling. Between the two risk groups, immune responses, immune cells, and immunological checkpoints were found to be considerably different. Conclusion: Overall, our findings indicate that the 5 ERS-related lncRNA signature was an excellent prognostic indicator and helped to predict the immunotherapy response for patients with LUAD.

Independent-effect comparison of five crosslinking procedures for Progressive Keratoconus based on Keratometry and the ABCD Grading System using Generalized Estimating Equations (GEE).

PURPOSE: Corneal collagen crosslinking (CXL) is an effective treatment for progressive keratoconus. Multiple CXL modalities are clinically available. The present study compared the 1 year outcomes of five types of CXL procedures for progressive keratoconus in a Chinese population using generalized estimating equations (GEE). METHODS: This retrospective study included 239 eyes in 171 patients with keratoconus who underwent CXL and were followed up for 1 year. Five CXL procedures were assessed, including Accelerated Transepithelial CXL, Iontophoresis CXL for 10 min, CXL plus phototherapeutic keratectomy (CXL-plus-PTK), High-Fluence Accelerated CXL, and Accelerated CXL. Patients treated with the Accelerated CXL procedure represented the reference group. Primary outcomes were visual acuity change, spherical equivalence, endothelial cell density, mean keratometry (Kmean), maximum keratometry (Kmax), minimum corneal thickness (MCT), and the ABCD Grading System, consisting of A (staging index for ARC; ARC = anterior radius of curvature), B (staging index for PRC, PRC = posterior radius of curvature), and C (staging index for MCT) values 1 year postoperatively compared to baseline. Secondary outcomes were corrected GEE comparisons from each procedure versus the Accelerated CXL group. RESULTS: The Accelerated Transepithelial CXL group had lower performance than the Accelerated CXL group according to Kmean and Kmax. The CXL-plus-PTK group performed significantly better than the reference group as reflected by Kmax (ß = -0.935, P = 0.03). However, the CXL-plus-PTK group did not perform as well for B and C, and the Iontophoresis CXL group performed better for C. CONCLUSIONS: The CXL-plus-PTK procedure was more effective than the Accelerated CXL procedure based on Kmax, and the Iontophoresis CXL procedure performed better on the C value based on the ABCD Grading System.

A novel analysis of Scheimpflug total corneal refractive power following corneal cross-linking in mild to moderate keratoconus.

AIM: To detect an earlier improvement in mild to moderate keratoconus following corneal cross-linking (CXL) with total corneal refractive power (TCRP) using ray tracing method. METHODS: A total of 40 eyes of 30 consecutive patients who underwent CXL for progressive keratoconus were retrospectively enrolled. The following keratometric parameters provided by Pentacam HR, including maximum keratometry (Kmax), steepest keratometry (Ksteep), 3 mm zonal TCRP centered over corneal apex (TCRPapex,zone 3 mm), zonal mean keratometry and TCRP centered over corneal cone (Kmcone,zone and TCRPcone,zone 1, 2, 3 mm) were evaluated preoperatively and 1, 3, 6, and 12mo postoperatively. Groups 1 and 2 were defined based on Kmax at postoperative 1mo as improved (the initial improvement group) or worsen (the initial deterioration group) compared to the preoperative level. RESULTS: In the overall group, only keratometric parameters based on ray tracing method displayed significant improvement early at 3mo postoperatively, in which TCRPcone,zone 1 mm and 2 mm exhibited the largest flattening (0.57 D and 0.53 D, respectively). In Group 1, only Kmax, Kmcone,zone 2 mm and TCRPcone,zone 2 mm showed significant improvement initially at 1mo postoperatively, in which Kmax exhibited the largest improvement (1.05 D), followed by TCRPcone,zone 2 mm (0.82 D). In Group 2, only keratometric parameters based on ray tracing method and Kmcone,zone 3 mm showed slight but not significant improvement early at 3mo, in which TCRPcone,zone 3 mm displayed the most improvement (0.19 D), followed by TCRPcone,zone 2 mm (0.15 D). CONCLUSION: The findings indicate that a 2 mm zonal TCRP centered over Kmax could earlier detect keratometric improvement by CXL compared to other commonly used parameters in mild to moderate keratoconic eyes.

Assessment of Corneal Pachymetry Distribution and Morphologic Changes in Subclinical Keratoconus with Normal Biomechanics.

PURPOSE: To investigate the pachymetry distribution of central cornea and morphologic changes in subclinical keratoconus with normal biomechanics and determine their potential benefit for the screening of very early keratoconus. METHODS: This retrospective comparative study was performed in 33 clinically unaffected eyes with normal topography and biomechanics from 33 keratoconus patients with very asymmetric ectasia (VAE-NTB; Corvis Biomechanical Index defined) and 70 truly normal eyes from 70 age-matched subjects. Corneal topographic, tomographic, and biomechanical metrics were measured using Pentacam and Corvis ST. The distance and pachymetry difference between the corneal thinnest point and the apex were defined as DTCP-Apex and DPTCP-Apex, respectively, to evaluate the pachymetry distribution within the central cornea. The discriminatory power of metrics was analysed via the receiver operating characteristic curve. A logistic regression analysis was used to establish predictive models. RESULTS: The parameters, DTCP-Apex and DPTCP-Apex, were significantly higher in VAE-NTB than those in normal eyes. For differentiating normal and VAE-NTB eyes, the Belin-Ambrósio deviation (BAD-D) showed the largest area under the curve (AUC; 0.799), followed by ARTmax (0.798), DTCP-Apex (0.771), tomography and biomechanical index (0.760), maximum pachymetry progression index (PPImax, 0.756), DPTCP-Apex (0.753), and back eccentricity (B_Ecc, 0.707) with no statistically significant differences among these AUCs. In the VAE-NTB group, the parameter B_Ecc was significantly and positively correlated with DTCP-Apex (P=0.011) and DPTCP-Apex (P=0.035), whereas the posterior elevation difference had a significant positive association with DPTCP-Apex (P=0.042). A model using the indices DTCP-Apex, B_Ecc, PPImax, and index of height asymmetry demonstrated the highest AUC of 0.846 with 91.43% specificity. CONCLUSIONS: Abnormal pachymetry distribution within the central cornea and subtle morphologic changes are detectable in subclinical keratoconus with normal biomechanics. This may improve VAE-NTB eyes detection.