Neoadjuvant Immunotherapy in Oncogene-Positive Non-Small Cell Lung Cancer: A Multicenter Study.

BACKGROUND: Preoperative immunotherapy has shed light on the management of resectable non-small cell lung cancer (NSCLC). However, whether neoadjuvant immunotherapy benefits patients with oncogene-positive NSCLC remains unknown. METHODS: Data were retrieved from 4 institutions in the period from August 2018 to May 2021. Eligible patients were aged ≥18 years with histologically confirmed stage IIA to stage IIIB (T1-2 N1-2 or T3-4 N0-2) NSCLC that was deemed to be surgically resectable. The neoadjuvant regimen included immune checkpoint inhibitors alone or in combination with platinum-based doublets. Surgical resection was performed 4 to 6 weeks after the first day of the last cycle of treatment. The primary end point was major pathologic response (MPR; ≤10% viable tumor cells). Analyses were categorized according to the patients' oncogene (EGFR, ALK, KRAS, MET, BRAF, ROS1, RET) status. RESULTS: Overall, 137 patients were identified; 46 (33%) patients had nonsquamous cell cancer, and 114 (83%) had stage IIIA/B disease. Oncogene alterations were identified in 22 (16%) patients, of whom only 2 patients (2/22 [9%]) had an MPR compared with 65 (65/115 [56.5%]) in the oncogene-negative population (P < .001). Similar results were retained after propensity score matching for age, sex, smoking status, histologic type, stage, and cycles of neoadjuvant treatment. Squamous cell carcinoma (odds ratio, 2.54; 95% CI, 1.08-5.99) and positive oncogene status (odds ratio, 0.13; 95% CI, 0.03-0.64) were found to be indicators for MPR by logistic regression. The 1-year event-free survival rate was 75.4% in the oncogene-positive group, which was not significantly different from 85.5% in the oncogene-negative population (P = .23). CONCLUSIONS: Patients with stage II-III oncogene-positive NSCLCs respond less than patients with oncogene-negative NSCLCs after neoadjuvant immunotherapy.

Expression, Clinical Significance, Immune Infiltration, and Regulation Network of miR-3940-5p in Lung Adenocarcinoma Based on Bioinformatic Analysis and Experimental Validation.

Background: Based on bioinformatics analysis and experimental validation, we investigated the expression, clinical significance, immune infiltration, and potential signaling pathways of miR-3940-5p in lung adenocarcinoma (LUAD). Methods: 521 LUAD tissue samples and 46 normal lung tissue samples from The Cancer Genome Atlas (TCGA) database. We evaluated the relationship between clinical features and miR-3940-5p expression using Kruskal-Wallis, Wilcoxon sign-rank, and logistic regression, explored the relationship between miR-3940-5p expression and the prognosis of LUAD patients using Kaplan-Meier survival curve analysis. Several databases were used to identify miRNA targets. MiR-3940-5p target genes were analyzed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The significant role of miR-3940-5p in function was evaluated using immune infiltration analysis. LUAD cell lines were tested for miR-3940-5p expression using QRT-PCR. Results: There was a significant association between high miR-3940-5p expression in LUAD and T stage (P=0.005), pathologic stage (P=0.047), race (White vs Asian & Black or African American) (P=0.041), residual tumor (P=0.043), and anatomic neoplasm subdivision2 (P=0.030). MiR-3940-5p expression predicted poor overall survival (HR: 1.35; 95% CI: 1.01-1.81; P=0.045), disease-specific survival (HR: 1.53; 95% CI: 1.05-2.23; P=0.026), and progression-free survival (HR: 1.35; 95% CI: 1.03-1.77; P=0.032). BAP1, BBS1, CCR2, KCNE3, PEBP1, and RABL2A were all associated with poor OS in LUAD patients with low miR-3940-5p expression levels. According to GO and KEGG analyses, miR-3940-5p may play a role in LUAD development by regulating pathways such as measles, PI3K-Akt signaling pathway, and p53 signaling pathway. There was a correlation between the expression level of miR-3940-5p and immune infiltration. LUAD cell lines showed significantly higher levels of miR-3940-5p than Beas-2B cells. Conclusion: A high expression of miR-3940-5p is significantly associated with a poor prognosis in patients with LUAD, suggesting that it could be used as a prognostic biomarker.

LncRNA ADAMTS9-AS2 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Lung Adenocarcinoma.

BACKGROUND: The role of long noncoding RNA (LncRNA) ADAMTS9 antisense RNA 2 (ADAMTS9-AS2) is unclear in lung adenocarcinoma (LUAD). The aim of this study was to explore the relationship between ADAMTS9-AS2 and LUAD, based on The Cancer Genome Atlas (TCGA) database and bioinformatics analysis. METHODS: Various statistical methods, Kaplan-Meier method, Cox regression analysis, GSEA, and immune infiltration analysis were used to evaluate the relationship between clinical features and ADAMTS9-AS2 expression, prognostic factors, and the significant involvement of ADAMTS9-AS2 in function. RESULTS: In LUAD patients, low expression of ADAMTS9-AS2 was associated with N stage (P=0.011), gender (P=0.002), number of packs smoked (P=0.024) and smoker (P<0.001). Low ADAMTS9-AS2 expression predicted a poorer overall survival (OS) (HR: 0.68; 95% CI: 0.51-0.91; P=0.01). And ADAMTS9-AS2 expression (HR: 0.626; 95% CI: 0.397-0.986; P=0.043) was independently correlated with OS in LUAD patients. Unwinding of DNA, extrinsic pathway, polo-like kinase-mediated events, cori cycle, MCM pathway, proteasome pathway, lagging strand synthesis and PCNA-dependent long patch base excision repair were differentially enriched in ADAMTS9-AS2 high expression phenotype. ADAMTS9-AS2 expression was correlated with certain immune infiltrating cells. CONCLUSION: In LUAD patients, ADAMTS9-AS2 expression was significantly associated with poor survival and immune infiltration. ADAMTS9-AS2 may be a promising biomarker of prognosis and response to immunotherapy for LUAD.

Modified inflammation-based score as an independent malignant predictor in patients with pulmonary focal ground-glass opacity: a propensity score matching analysis.

Pulmonary focal Ground-glass Opacities (fGGOs) would frequently be identified after widely implementation of low-dose computed tomography (LDCT) screening. Because of the high false-positive rate of LDCT, antibiotics should be regarded as advocates in clinical management for detected fGGOs. Retrospectively review consecutive patients with fGGOs between August 2006 and August 2012. Then, relative Glasgow prognostic score (GPS) were constructed in three different systems, traditional GPS system (tGPS), modified GPS system 1 (m1GPS), and modified GPS system 2 (m2GPS). Moreover, propensity score matching (PSM) was employed in balancing baseline covariates. After PSM, patients were matched and included in benign and malignant groups as 1:1 ratio. All reported parameters were balanced in both groups and no statistical differences could be detected. Finally, m1GPS exhibited remarkable different distribution between benign and malignant fGGOs. In detail, m1GPS 1 was more frequently observed in benign fGGOs nodules, while m1GPS 2 in malignant fGGOs nodules. Modified inflammation-based score was identified as an independent predictor of malignancies in patients with pulmonary fGGOs. Patients with m1GPS 1 were more likely to be benign fGGOs, while victims with m1GPS 2 more likely to be malignant.

Nomogram to Predict Occult N2 Lymph Nodes Metastases in Patients With Squamous Nonsmall Cell Lung Cancer.

For nonsmall cell lung cancer (NSCLC) patients without distant metastases, occult involvement of N2 lymph nodes would be of the utmost importance in determining both treatment and survival. The key to optimal treatment strategies relied on accurate diagnosis, in particular accurate clinical tumor staging. Patients with clinical N0 or N1 staging preoperatively had a sizeable risk to have occult N2 lymph nodes metastases.From November 2004 to March 2007, the entire database in a tertiary hospital of all patients with a pathologic diagnosis of squamous NSCLC underwent anatomical pulmonary resection and systematic mediastinal lymph node dissection were retrospectively collected and reviewed. A nomogram was developed on the basis of a multivariable logistic regression model with a combination of all potential variables. In order to surmount the potential of overestimating predictive performance, both bootstrapping for internal validation and an independent external validation set were employed.A nomogram incorporating the significant risk factors was created to predict the probability of occult N2 lymph nodes metastases. The calibration plot for the probability of occult N2 lymph nodes metastases showed an optimal agreement between the predicted probabilities by nomogram and actual observed probabilities. An objective and accurate nomogram predictive model for occult N2 lymph nodes metastases was drawn up and validated internally and externally in patients with squamous NSCLC.The nomogram model, as a robust tool in predicting occult N2 lymph nodes involvement, could be involved in a cost-effective application of specific diagnostic and therapeutic strategies.

Combination of body mass index and oxidized low density lipoprotein receptor 1 in prognosis prediction of patients with squamous non-small cell lung cancer.

Lung cancer, especially non-small cell lung cancer (NSCLC), represents enormous challenges in continuously achieving treatment improvements. Besides cancer, obesity is becoming ever more prevalent. Obesity is increasingly acknowledged as a major risk factor for several types of common cancers. Significant mechanisms overlap in the pathobiology of obesity and tumorigenesis. One of these mechanisms involves oxidized low density lipoprotein receptor 1 (OLR1), as a link between obesity and cancer. Additionally, body mass index (BMI) has been widely used in exploiting the role of obesity on a series of diseases, including cancer. Significantly, squamous NSCLC revealed to be divergent clinical and molecular phenotypes compared with non-squamous NSCLC. Consequently, OLR1 immunostaining score and BMI were assessed by Fisher's linear discriminant analysis to discriminate if progression-free survival (PFS) would exceed 2 years. In addition, the final model was utilized to calculate the discriminant score in each study participant. Finally, 131 patients with squamous NCSLC were eligible for analysis. And a prediction model was established for PFS based on these 2 markers and validated in a second set of squamous NCSLC patients. The model offers a novel tool for survival prediction and could establish a framework for future individualized therapy for patients with squamous NCSLC.

Immunological markers predict the prognosis of patients with squamous non-small cell lung cancer.

Lung cancer has become the leading cause of cancer-related death worldwide. However, treatment failures still represent enormous challenges, and it is doubtful whether standard treatment modalities could continuously achieve substantial improvements. As one of the novel therapy strategies, PD-L1 has been shown the function of down-regulating T cell activation through receptor PD-1. Moreover, prognosis of cancer patients is based not only on tumor-related factors but also on host-related factors, particularly systemic inflammatory response. Significantly, squamous non-small cell lung cancer (NSCLC) revealed to be divergent clinical and molecular phenotypes compared with non-squamous NSCLC. Monocyte ratio, neutrophils to lymphocytes ratio, PD-L1 immunostaining score and PD-1-positive stained tumor-infiltrating lymphocyte counts were assessed by Fisher's linear discriminant analysis to discriminate whether overall survival (OS) would exceeding 5 years. Finally, a prediction model was established for OS based on these immunological markers. Furthermore, this prediction model was validated in a second set of squamous NSCLC patients. The model offers a novel tool for survival prediction and could have important clinical implications for patients with squamous NSCLC, thus providing a framework for future individualized therapy.

[Changes of electrical property of the twelve source-points in encephaloma patients before and after surgery].

OBJECTIVE: To observe the changes of electrical property of the 12 Source-points in encephaloma patients undergoing surgery. METHODS: A total of 116 encephaloma patients and 60 healthy people who signed the informed consent were enlisted in the present study. The regional cutaneous electric resistance (CER) of the bilateral 12 Yuan (Source)-points was measured in the afternoon (14:00-16:00) before and one week after surgery under room temperature [(22 +/- 3) degrees C, (55 +/- 10)% in humidity] by using "Meridian Energy Analysis Device". RESULTS: In comparison with normal subjects, CER values of the 12 Source-points on both sides of the body in encephaloma patients were significantly lower (P < 0.01). Before surgery, CER values of Wangu (SI 4), Taibai (SP 3), Taichong (LR 3) and Chongyang (ST 42) on the left side were significantly higher than those of the isonym points on the right side (P < 0.01, P < 0.05), suggesting an imbalance of the bilateral Small Intestine, Spleen, Liver and Stomach Meridians. After surgery, CER values of Shenmen (HT 7), Wangu (SI 4), Yangchi (SJ 4) and Taibai (SP 3) on the left side were markedly higher than those of the isonym points on the right side (P < 0.05, P < 0.01), suggesting an imbalance of the bilateral Heart, Small Intestine, Trienergizer and Spleen Meridians. Comparison between pre- and post-surgery showed that CER values of Taiyuan (LU 9), Daling (PC 7), Taibai (SP 3), Taichong (LR 3), Taixi (KI 3), Jinggu (BL 64), Qiuxu (GB 40) and Chongyang (ST 42) on both sides, and Wangu (SI 4) on the right side lessened obviously post-surgery (P < 0.01, P < 0.05), suggesting an imbalance of the bilateral meridians found in more meridians, including yang meridians entering the brain as the Bladder, Gallbladder, Stomach Meridians. CONCLUSION: In encephaloma patients, the CER values of some Source-points on the left side are significantly higher than those on the right side, suggesting an imbalance of the bilateral meridians in functional activities.