Clinical and genomic characterization of neutral tumor evolution in Head and Neck Squamous Cell Carcinoma.

Recent studies suggest that a significant proportion of cancers undergo neutral tumor evolution. We applied neutral evolution model in HNSCC patients from The Cancer Genome Atlas (TCGA). To ensure the accuracy of classification results, a sample with the purity of tumor <0.7 was excluded. A tumor sample was considered to evolve neutrally if R2 ≥ 0.98. We found that about 16% of HNSCC patients undergo neutral tumor evolution. We showed that neutral evolution HNSCC patients have better prognosis and higher activities of immune response pathways, and the numbers of co-occurring mutation events and significantly positive selection mutations are significantly less than non-neutral evolution HNSCC patients. In conclusion, we described a comprehensive clinical and genomic characteristics of neutral tumor evolution in Head and Neck Squamous Cell Carcinoma (HNSCC), and provided evidence that the evolution history of HNSCC has both clinical and biological implications.

Stair-Climbing Test Predicts Postoperative Cardiopulmonary Complications and Hospital Stay in Patients with Non-Small Cell Lung Cancer.

BACKGROUND There is currently no reliable method to predict major postoperative cardiopulmonary complications for patients with non-small cell lung cancer (NSCLC). In this study, we hypothesized that exercise oxygen desaturation (EOD) and heart rate change results in a stair-climbing test (SCT) would predict postoperative cardiopulmonary complications for patients with NSCLC. MATERIAL AND METHODS We examined 171 patients (41 females and 130 males) with NSCLC by preoperative SCT from January 2010 to July 2015. Among them, 27 underwent wedge resection, 122 underwent lobectomy, and 22 underwent pneumonectomy. The correlation between postoperative cardiopulmonary complications and parameters of SCT and pulmonary function test (PFT) parameters were analyzed retrospectively. RESULTS The overall 30-day postoperative morbidity of the patients was 46/171 (26.9%), with death occurring in 3/171(1.8%). The age, FEV1%, MVV, height of climbing, EOD, and heart rate change were found to be significantly different between the group with postoperative cardiopulmonary complications and those without. Binary logistic regression analysis showed that EOD and heart rate change were independently correlated with postoperative cardiopulmonary complications. In addition, a model predicting the probability of postoperative cardiopulmonary complication based on logistic regression for multivariable analysis was used to confirm our findings. CONCLUSIONS A symptom-limited SCT with oxygen saturation monitoring is a safe, simple, and low-cost method to evaluate cardiopulmonary function preoperatively.

[Comparison of the lymph node dissection and complications between video-assisted thoracoscopic (VATS) esophagectomy and conventional esophagectomy via right thoracotomic].

OBJECTIVE: Video-assisted thoracoscopic (VATS) esophagectomy has been performed for more than 10 years in China. However, compared with the conventional esophagectomy via right thoracotomy, whether VATS esophagectomy has more advantages or not in the lymph node (LN) dissection and prevention of perioperative complications is still controversial and deserves to be further investigated. The aim of this study was to explore whether there are significant differences in this issue between the two surgical modalities or not. METHODS: The results of lymph node dissection and perioperative complications as well as other parameters in the patients treated by VATS esophagectomy and those by conventional esophagectomy via right thoracotomy at our department from May 1, 2009 to July 30, 2013 were compared using SPSS 16.0 in order to investigate whether there was any significant difference between these two treatment modalities in the learning curve stage of VATS esophagectomy. RESULTS: One hundred and twenty-nine cases underwent VATS esophagectomy between May 1, 2009 and July 30, 2013, and another part 129 cases with the same preoperative cTNM stage treated by conventional esopahgectomy via right thoracotomy were selected in order to compare the results of lymph node dissection and perioperative complications as well as other parameters between those two groups of patients. There were no significant differences in the sex, age, lesion locations and cTNM stage between these two groups. The total LN metastatic rate in the VATS esophagectomy group was 35.7% and that of the conventional esophagectomy group was 37.2% (P > 0.05). The total average number of dissected lymph nodes was 12.1 vs. 16.2 (P < 0.001). The average dissected LN stations was 3.2 vs. 3.6 (P = 0.038). The total average number of dissected LN along the left recurrent laryngeal nerve was 2.0 vs. 3.7 (P = 0.012). The total average number of dissected LN along the right recurrent laryngeal nerve was 2.9 vs. 3.4 (P = 0.231). However, there was no significant difference in the total average number of dissected LN in the other thoracic LN stations, and in the perioperative complications between the two groups. The total postoperative complication rate was 41.1% in the VATS group versus 42.6% in the conventional group (P = 0.801). The cardiopulmonary complication rate was 25.6% vs. 27.1% (P = 0.777). The death rate was the same in the two groups (0.8%). The VATS group had less blood infusion (23.2% vs. 41.8%, P = 0.001) and shorter hospital stay (15.9 days vs. 19.2 days, P = 0.049) but longer operating time (161.3 min vs. 127.8 min, P < 0.01). CONCLUSIONS: In the learning curve stage of VATS esophagectomy, compared with the conventional esophagectomy, less LN number and stations can be dissected in the VATS group due to un-skillful VATS manipulation, especially it is more difficult in the LN dissection along the left recurrent laryngeal nerve. Therefore, it is more suitable to select patients with early esophageal cancer without obvious enlarged lymph nodes for VATS esophagectomy in the learning curve stage.

LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma.

BACKGROUND: Oesophageal cancer is one of the most deadly forms of cancer worldwide. Long non-coding RNAs (lncRNAs) are often found to have important regulatory roles. OBJECTIVE: To assess the lncRNA expression profile of oesophageal squamous cell carcinoma (OSCC) and identify prognosis-related lncRNAs. METHOD: LncRNA expression profiles were studied by microarray in paired tumour and normal tissues from 119 patients with OSCC and validated by qRT-PCR. The 119 patients were divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random Forest supervised classification algorithm and a nearest shrunken centroid algorithm, then validated in a test group and further, in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by multivariable Cox regression analysis. RESULTS: LncRNAs showed significantly altered expression in OSCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885.1, XLOC_013014 and ENST00000547963.1) which classified the patients into two groups with significantly different overall survival (median survival 19.2 months vs >60 months, p<0.0001). The signature was applied to the test group (median survival 21.5 months vs >60 months, p=0.0030) and independent cohort (median survival 25.8 months vs >48 months, p=0.0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for patients with OSCC. Stratified analysis suggested that the signature was prognostic within clinical stages. CONCLUSIONS: Our results suggest that the three-lncRNA signature is a new biomarker for the prognosis of patients with OSCC, enabling more accurate prediction of survival.

[Role of conventional pulmonary function tests and stair climbing test in the prediction of postoperative cardiopulmonary complications in non-small cell lung cancer patients after surgery].

OBJECTIVE: To evaluate and compare the value of stair climbing tests and conventional pulmonary function tests in the prediction of postoperative cardiopulmonary complications in non-small cell lung cancer patients underwent surgery. METHODS: From April 1, 2010 to Jan. 30, 2012, a total of 162 patients with thoracic carcinoma underwent stair climbing test (SCT) and conventional pulmonary function tests (PFT) preoperatively. The correlation of postoperative cardiopulmonary complications with the SCT and PFT parameters were analyzed retrospectively using chi-square test, independent sample t test and binary logistic regression analysis. RESULTS: Of the 162 patients, 19 without operation were excluded, due to an advanced stage (9 cases), poor cardiopulmonary function (5 cases), rejecting operation (4 cases) and exploration alone (1 case). 143 cases were eligible and evaluated eventually. Forty-one of the 143 patients (28.7%) had postoperative cardiopulmonary complications, but no death occurred. The patients were stratified into groups based on the time of stair climbing 5 stories (18.36 m, t, <92 s, ≥ 92 s). Exercise oxygen desaturation (EOD) during the stair climbing test (<5%, ≥ 5%) and the difference between the pulse at resting state and the pulse at end of stair climbing test (ΔP, <55 beats/min, ≥ 55 beats/min), respectively. The rate of postoperative cardiopulmonary complications was significantly higher in the group with t ≥ 92 s, EOD ≥ 5% and ΔP < 55 beats/min (38.5%, 42.0% and 35.1%, respectively) than that in the group with t<92 s, EOD<5% and ΔP ≥ 55 beats/min (16.9%, 21.5% and 18.2%, respectively). Binary logistic regression analysis showed that postoperative cardiopulmonary complications were independently correlated with EOD and lung function which did not meet the requirement of the lung resection operation mode. CONCLUSIONS: A symptom-limited stair climbing test is a safe, simple and low-cost method to evaluate the cardiopulmonary function preoperatively. It can predict the occurrence of postoperative cardiopulmonary complications in non-small cell lung cancer patients. Conventional pulmonary function tests and stair-climbing test can be recommended to be routinely performed in all patients with non-small cell lung cancer before thoracic surgery.

Multiple micromeningiomas coexist with primary lung adenocarcinoma: A case report.

Cases of multiple ectopic meningiomas in the lung coexisting with pulmonary malignancies are extremely rare in the clinic. On imaging, it is difficult to distinguish multiple ectopic meningiomas from lung cancer, which puts forward higher requirements for treatment. A 65-year-old female patient was admitted to our department for multiple nodules in both lungs. The patient underwent thoracoscopic wedge resection and segmental resection. Postoperative pathological examination found lung meningioma, atypical adenomatoid hyperplasia (AAH), carcinoma in situ (AIS), invasive adenocarcinoma, and other pathological types. In this case, pulmonary meningioma, AAH, AIS, and invasive adenocarcinoma of various pulmonary nodules were observed. This case, which has not been reported before, is unique in that it has multiple pathologic types in one organ. This puts forward higher requirements for clinical diagnosis and treatment.

Combination of STING agonist and CXCR3 antagonist disrupts immune tolerance to overcome anti-PD-L1 resistance in lung adenocarcinoma under oxidative stress.

We investigated the role of the STING1-CXCR3 axis using database data and verified it in a mouse model bearing Lewis lung carcinoma (LLC) cells exposed to hydrogen peroxide (H2O2). Mice were treated with STING agonist liposomes (STING-Lip), anti-programmed death-ligand 1 (PD-L1), or STING-Lip + anti-PD-L1. The database data revealed that immune response pathways were enriched in patients with lung adenocarcinoma with upregulated STING1 signaling. Upregulated STING1 signaling was associated with a high abundance of immunoregulatory and effector molecules, cytokines, activated CD8+ T cells, and M1 macrophages in patients with lung adenocarcinoma. In this study, H2O2-treated LLC cells promoted an immunosuppressive microenvironment and enhanced tumor growth in mice. STING-Lip inhibited distant, untreated, and H2O2-induced LLC growth by activating systemic immunity. STING-Lip + anti-PD-L1 failed to slow distant and untreated LLC growth, whereas STING-Lip + anti-PD-L1 + CXCR3 antagonist inhibited distant tumor growth in mice. The combination of STING1 activation and CXCR3 inhibition may be a novel immunotherapeutic strategy to overcome immune checkpoint inhibitor resistance in lung adenocarcinoma by activating systemic immunity in the tumor microenvironment under oxidative stress.

[Comparison of the results of lymph node dissection via left versus right thoracotomy].

OBJECTIVE: Up to now surgical treatment has been still the most effective treatment for esophageal cancer. However, postoperative lymph node recurrence is still a frequent event and affects long term survival considerably. The aim of this study is to compare the results of lymph node dissection via left vs. right thoracotomies and to verify whether there is any essential difference in lymphadenectomy between these two approaches. METHODS: Five hundred and fifty-nine cases with thoracic esophageal cancer were randomly selected from the database of esophageal cancer patients who underwent surgical treatment in our hospital between May 2005 and January 2011, including 282 cases through left thoracotomy and 277 cases through right thoracotomy. This series consisted of 449 males and 110 females with a mean age of 58.8 years (age range: 36 - 78 years). The pathological types were mainly squamous cell carcinoma (548 cases) and other rare types (11 cases). The data were analyzed and compared using Chi-square test. The P-value < 0.05 was considered as statistically significant. The actual 5-year survival rate was calculated based on the recent follow-up data of the patients who underwent surgery at least 5 years ago. RESULTS: The average number of dissected lymph nodes was 23.4 via left versus 24.6 via right thoracotomies. The overall lymph node metastasis rate was 48.9% via left thoracotomy and 53.8% via right thoracotomy, and 34.8% vs. 50.5% in the chest (P < 0.001), 29.1% vs. 17.7% in the abdomen (P = 0.001). The pathologically confirmed lymph node metastasis rate was 45.9%, 44.0% and 34.9% in the upper, middle and lower segments of thoracic esophagus, respectively. The lymph node metastasis rates detected via left and right thoracotomy in the stage T1 cases were 14.7% (5/34) vs. 42.9% (12/28) (P < 0.001), and in the stage T2 cases were 35.4% (17/48) vs. 52.8% (28/53) (P = 0.007); in the station of para-thoracic esophagus were 9.6% vs. 13.4%, in the left upper mediastinum were 2.1% vs. 7.6%, and in the right upper mediastinum were 1.4% vs. 26.0%, respectively. The preliminary actual 5-year survival rate was 38.2% in the cases via left thoracotomy vs. 42.1% in those via right thoracotomy. CONCLUSIONS: The results of this study demonstrate that lymph node dissection is more complete via right thoracotomy than via left thoracotomy, especially for the tracheoesophageal groove and para-recurrent laryngeal nerve nodes, which may eventually improve the survival of patients with esophageal cancer. Therefore, surgical treatment via right thoracotomy by Ivor-Lewis (two incisions) mode or Levis-Tanner (three incisions) mode with two-field or three-field complete lymph node dissection may become prevalent in the future.

[Surgical treatment of sternal tumors: resection of the tumors and reconstruction of the chest wall defects].

OBJECTIVE: To investigate the efficacy of surgical treatment of sternal tumors and repairing methods of the chest wall defects. METHODS: Fifteen patients with sternal tumors were diagnosed and underwent resection of the sternal tumors according to the en-bolck principle and repair of the chest wall defects using various materials from January 1968 to December 2010 in our hospital. RESULTS: Of 6 patients with sternal manubrim tumors, one patient had reconstruction only with steel wire, other 5 patients healed completely after repair with soft materials. Of 7 patients with sternal body tumors, one patient recovered quickly without reconstruction because he had only partial resection; four patients had chest wall repair with soft materials, but they breathed hardly; and two patients had chest wall reconstruction with rigid materials. One patient had ventilatory support, another patient recovered quickly. Ventilatory support was needed in two patients treated by subtotal sternectomy because they had chest wall repair with soft materials. CONCLUSIONS: In surgical treatment of sternal tumors by manubrim sternetomy, the chest wall defects can be constructed with soft materials. After resection of sternal body tumors and subtotal sternectomy, the thoracic wall defects need to be reconstructed with rigid materials.

Registered Clinical Trials for Artificial Intelligence in Lung Disease: A Scoping Review on ClinicalTrials.gov.

Clinical trials are the most effective tools to evaluate the advantages of various diagnostic and treatment modalities. AI used in medical issues, including screening, diagnosis, and treatment decisions, improves health outcomes and patient experiences. This study's objective was to investigate the traits of registered trials on artificial intelligence for lung disease. Clinical studies on AI for lung disease that were present in the ClinicalTrials.gov database were searched, and fifty-three registered trials were included. Forty-six (72.1%) were observational trials, compared to seven (27.9%) that were interventional trials. Only eight trials (15.4%) were completed. Thirty (56.6%) trials were accepting applicants. Clinical studies often included a large number of cases; for example, 24 (32.0%) trials included samples of 100-1000 cases, while 14 (17.5%) trials included samples of 1000-2000 cases. Of the interventional trials, twenty (15.7%) were retrospective studies and twenty (65.7%) were prospective studies.

A huge Ewing's sarcoma of the rib presenting with superior vena cava syndrome and dysphagia.

A 24-year-old male patient was admitted to our center complaining of dizziness (superior vena cava syndrome [SVCS]), dysphagia and pain in the right chest wall. At the initial diagnosis, the patient had been found to have an irregular shaped 35 × 30 × 27 cm mass in the right side of his chest. On November 12, 2019, this patient received surgery in our center. The right sixth rib and the tumor were completely removed (R0), while preserving all the lung tissue and other organs in the chest. The patient recovered well after surgery, and his right lung was fully expanded.

Ureteral metastasis from pulmonary adenocarcinoma: A case report and literature review.

The occurrence of ureteral metastasis from distant primary tumors is uncommon, and appears to be especially rare when it originates from the lungs. In the case presented here, a patient with lumbago and left hydronephrosis was diagnosed with left ureteral metastasis of pulmonary adenocarcinoma after a CT-guided percutaneous transthoracic needle biopsy of the lung and retroperitoneal laparoscopic left nephroureterectomy. He accepted the targeted therapy because the lung tumor epidermal growth factor receptor mutation (exon19 deletion) was positive, and preoperative staging of lung adenocarcinoma was stage IVA. After an 8-month follow-up, he is still alive and well, with no local recurrence or distant metastases. The therapy outcome assessment is stable disease. Although rare, our case has demonstrated that pulmonary adenocarcinoma has the possibility of metastasizing to the ureter, a risk that should be considered in some lung cancer patients.

Clinical Trials for Artificial Intelligence in Cancer Diagnosis: A Cross-Sectional Study of Registered Trials in ClinicalTrials.gov.

Objective: Clinical trials are the most effective way to judge the merits of diagnosis and treatment strategies. The in-depth mining of clinical trial data enables us to grasp the application trend of artificial intelligence (AI) for cancer diagnosis. The aim of this study was to analyze the characteristics of registered trials on AI for cancer diagnosis. Methods: Clinical trials on AI for cancer diagnosis registered on the ClinicalTrials.gov database were searched and downloaded. Statistical analysis was performed by using SPSS 20.0 software. Results: A total of 97 registered trials were included. Of them, only 27 (27.8%) were interventional trials and 70 (72.1%) were observational trials. Fifteen (15.4%) trials had been completed. Fifty trials were in recruitment, and another 18 remained unrecruited. The number of cases included in the clinical trials tended to be large, 31 (32.0%) trials including samples ranging from 100 to 499 cases and 17 (17.5%) trials including samples ranging from 500 to 999 cases. Of the 27 interventional trials, only two trials reported trials' phase. Most (85.2%) interventional trials were for diagnosis, and a few (3.7%) were for the purpose of both the diagnosis and therapy of cancers. For the observational clinical trials, 46 (65.7%) were cohort studies, and 11 (15.7%) were case-only studies. Among the observational trials, 46 (65.7%) were prospective studies and 13 (18.6%) were retrospective studies. Among 97 trials, 37 (38.1%) involved colorectal cancer, 11 (11.3%) involved breast cancer, 43 (44.3%) were for imaging diagnosis, 33 (34.0%) were for endoscopic diagnosis, and 11 (11.3%) were for pathological diagnosis. For the interventional trials, 11 trials were parallel assignment (40.7%), and 14 were single group assignment (51.9%). Among the 27 interventional trials, 18 (66.7%) trials were performed without masking, 6 (22.2%) trials were performed with single masking, only 1 (3.7%) was performed with double masking, and 2 (7.4%) was performed with triple masking. Conclusion: It appears that most registered trials on AI for cancer diagnosis are observational design, and more trials are needed in this field.

LincRNA00494 Suppresses Non-small Cell Lung Cancer Cell Proliferation by Regulating SRCIN1 Expression as a ceRNA.

Background: Lung cancer is the most common malignant tumor worldwide. Accumulating results have shown that long non-coding RNAs (lncRNAs) play a key role in tumorigenesis. Patients and Methods: A total of 163 tumor tissues were collected from non-small cell lung cancer (NSCLC) patients from West China Hospital of Sichuan University. LincRNA00494 is a novel lncRNA, and its expression and biological effect in NSCLC were reported in this study. NSCLC cell lines were used in this study. Results: LincRNA00494 is mainly distributed in the cytoplasm. LincRNA00494 was downregulated in the tumor tissues compared with the adjacent non-tumor tissues. LincRNA00494 expression was positively correlated with SRCIN1 expression (R = 0.57, P < 0.05). Silencing of LincRNA00494 in the cell lines substantially decreased SRCIN1 expression at the mRNA and protein levels, whereas overexpression of LincRNA00494 enhanced the SRCIN1 levels. miR-150-3p significantly decreased the luciferase signals of LincRNA00494 and SRCIN1 reporters. After transfection with miR-150-3p mimics and miR-150-3p inhibitor, overexpression of LincRNA00494 decreased the proliferation of the H358 (36%) and H1299 (29%) cell lines compared with that of the control cells, as shown by CCK-8 assays, whereas silencing LincRNA00494 promoted the proliferation of the H358 (47%) and H1299 (35%) cells. Tumor growth from LincRNA00494-overexpressing xenografts was significantly decreased; additionally, LincRNA00494 silencing substantially increased tumor growth compared with that of the control cells. Conclusions: Functional experiments revealed that LincRNA00494 inhibited NSCLC cell proliferation, which might be related to the suppression of SRCIN1, a tumor suppressor gene, by acting as a decoy for miR-150-3p. The data showed that LincRNA00494 might have antineoplastic effects during NSCLC tumorigenesis through its role as a ceRNA.

Advances in Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer Based on Accurate Molecular Typing.

The essence of precision medicine is to achieve the goal of "individualized treatment" through genotyping of patients and targeted therapy. At present, the pathogenic genes of non-small cell lung cancer (NSCLC) have been studied most thoroughly and targeted therapy based on genotyping has been the most successful. This paper focuses on the precision treatment of NSCLC based on genotyping, comparing gene detection methods and summarize the latest progress of NSCLC immunotherapy.

Circulating tumor cells in pulmonary vein and peripheral arterial provide a metric for PD-L1 diagnosis and prognosis of patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of death caused by malignant tumors. PD-L1(programmed cell death protein-1) has shown tremendous achievement in treating NSCLC. We sought to find the relationship between CTCs in the pulmonary vein and postoperative PFS, besides we detected PD-L1 in CTCs. METHOD: We enrolled 112 NSCLC patients. CTC tests were performed at four time points (preoperative, pulmonary vein, intraoperative and postoperative) on every NSCLC patient who received surgery. The RNA of PD-L1 was tested by FISH. The levels of the PD-L1 mRNA and protein in tissue samples were detected. RESULTS: The CTCs in the PV were the highest (P< 0.001), and CTCs in the PPA were the lowest (P< 0.001). The PFS in the group with PV CTCs≥ 16/5 ml was shorter than that in the group with PV CTCs< 16/5 ml (11.1 months vs 21.2 months, respectively; P< 0.001). The PFS in the group with PPA CTCs≥ 3/5 ml was shorter than that in the group with CTCs< 3/5 ml (14.8 months vs 20.7 months, respectively; P< 0.001). The CTCs in stage I were lower than those in stage II-IV (P = 0.025). No linear relationship was found between the CTCs and tumor size (P> 0.05) or LN metastasis (P> 0.05). In total, fifty-two (50.5%) patients had positive PD-L1 expression in CTC. In PD-L1-positive CTC patients, the value of PD-L1 tissue expression was higher than that in PD-L1-negative CTC patients (P = 0.0153). CONCLUSION: CTCs in the pulmonary vein can be an effective prognosis indicator of NSCLC patients.

Detection of Circulating Tumor Cell Molecular Subtype in Pulmonary Vein Predicting Prognosis of Stage I-III Non-small Cell Lung Cancer Patients.

Background: There was rare studies on prognosis of pulmonary venous CTC and early or advanced NSCLC patients. We want to investigate whether CTCs and the subtype of it can predict the prognosis of NSCLC patients. Patients and Methods: One hundred and fourteen patients with stage I-III NSCLC were included CanPatrol™ CTC analysis. PD-L1 expression level were detected in CTC of pulmonary vein. PD-L1, number of CTC in pulmonary, CTC's subtype, clinical characteristics, prognosis of patients were analyzed. Results: 110/114 (96.5%) patients could be found CTCs in pulmonary vein, 58/114 (50.9%) patients had CTC≥15/ml in pulmonary vein, 53/110 patients (48.2%) were defined as having MCTC subtype and 56/110 patient were found have PD-L1 (+) CTC in pulmonary vein. Multivariate analyses showed that PVCTC, MCTC, and stage were independent factors of DFS (P < 0.05). No OS difference was found between number of CTC (P = 0.33) and other CTC factors (P > 0.05), only stage was independent factor of OS (P = 0.019). There were decreases of CTC number and MCTC number in EGFR mutant subgroup (P = 0.0009 and P = 0.007). There were increases of CTC (P = 0.0217), MCTC (P = 0.0041), and PD-L1 (+) CTC (P = 0.0002) number in KRAS mutant subgroup. There was increase of MCTC (P =0.0323) number in BRAF mutant. There were fewer CTCs in pulmonary vein for patients with EGFR mutant than in patients with full wild-type gene (P = 0.0346). There were more PD-L1 positive CTCs in pulmonary vein for patients with ALK rearrangement, KRAS mutant, BRAF mutant, or ROS1 mutant than in patients with full wild-type gene (P = 0.0610, P = 0.0003, P = 0.032, and P = 0.0237). There were more mesenchymal CTCs in pulmonary vein for patients with KRAS mutant and BRAF mutant than in patients with full wild-type gene (P = 0.073 and P = 0.0381). There were fewer mesenchymal CTCs in pulmonary vein for patients with EGFR mutant than in patients with full wild-type gene (P = 0.0898). Conclusions: The patients with high number of CTCs, MCTCs, or PD-L1 (+) CTCs in pulmonary vein experienced poor prognosis of DFS. There are obvious correlations between the CTC subtype of NSCLC and the gene subgroups of tumor tissue.

Precise Prediction of Calpain Cleavage Sites and Their Aberrance Caused by Mutations in Cancer.

As a widespread post-translational modification of proteins, calpain-mediated cleavage regulates a broad range of cellular processes, including proliferation, differentiation, cytoskeletal reorganization, and apoptosis. The identification of proteins that undergo calpain cleavage in a site-specific manner is the necessary foundation for understanding the exact molecular mechanisms and regulatory roles of calpain-mediated cleavage. In contrast with time-consuming and labor-intensive experimental methods, computational approaches for detecting calpain cleavage sites have attracted wide attention due to their efficiency and convenience. In this study, we established a novel computational tool named DeepCalpain (http://deepcalpain.cancerbio.info/) for predicting the potential calpain cleavage sites by adopting deep neural network and the particle swarm optimization algorithm. Through critical evaluation and comparison, DeepCalpain exhibited superior performance against other existing tools. Meanwhile, we found that protein interactions could enrich the calpain-substrate regulatory relationship. Since calpain-mediated cleavage was critical for cancer development and progression, we comprehensively analyzed the calpain cleavage associated mutations across 11 cancers with the help of DeepCalpain, which demonstrated that the calpain-mediated cleavage events were affected by mutations and heavily implicated in the regulation of cancer cells. These prediction and analysis results might provide helpful information to reveal the regulatory mechanism of calpain cleavage in biological pathways and different cancer types, which might open new avenues for the diagnosis and treatment of cancers.

Intrapulmonary lymph node metastasis is common in clinically staged IA adenocarcinoma of the lung.

BACKGROUND: Intrapulmonary lymph nodes (LNs, stations 11-14) are usually omitted in postoperative pathological examination. Some non-small cell lung cancer (NSCLC) patients with intrapulmonary LN metastasis are incorrectly diagnosed as N0 cases. Furthermore, underestimation of intrapulmonary LN involvement in clinically early stage NSCLC may lead to the incorrect choice of surgical procedure: lobectomy or sublobar resection. This study was conducted to determine the status of intrapulmonary LN involvement in clinically staged IA (c-T1N0M0) peripheral adenocarcinoma of the lung. METHODS: Seventy-five lobectomy specimens of c-T1N0M0 peripheral adenocarcinoma of the lung were carefully dissected to find intrapulmonary LNs. The longest diameter of each intrapulmonary LN was measured and sent for pathological examination, together with hilar and mediastinal LNs, to investigate the relationship between LN metastasis and primary tumor size. RESULTS: Intrapulmonary LN metastasis was detected in 22.7%(17/75) of patients. Positive LNs were detected in 21.7% (10/46) of T1b patients and 45% (11/24) of T1c patients, while no metastasis (0/5) was observed in T1a patients (P = 0.036). The mean longest diameter of the 17 involved intrapulmonary LNs was only 6.5 ± 2.1 mm, which was not significantly different to the size of negative intrapulmonary LNs (5.2 ± 1.4 mm). CONCLUSIONS: Intrapulmonary LN metastasis is common in clinically staged IA peripheral adenocarcinoma of the lung. LN metastasis is related to tumor size, and this should be taken into account to determine appropriate surgical procedures and postoperative treatment. Computed tomography is not a reliable method to judge LN metastasis, particularly intrapulmonary LN metastasis.

Advances in evidence-based medicine for immunotherapy of non-small cell lung cancer.

Tumor immunotherapy is praised as "green therapy," which can attack tumor by mobilizing immune system. By removing the inhibition of immune cells, checkpoint inhibitors help T cells to identify and kill tumor cells. In recent years, more and more attention has been paid to its effectiveness as a tumor therapy with a large number of clinical data. Currently, inhibitors of 2 checkpoints, CTLA-4 and PD-1/PD-L1, have been approved to be listed. In particular, the latter has achieved breakthrough progress in non-small cell lung cancer in recent years, bringing about changes in the therapeutic strategy of lung cancer, as well as challenges to the evaluation criteria. This article focuses on the latest immunotherapy methods for lung cancer. The purpose of this article is to summarize the development of evidence-based medicine for lung cancer immunotherapy and to provide help for further understanding of lung cancer immunotherapy.