Lilan Zhao

Introduction: The impact of rib invasion on the non-small cell lung cancer (NSCLC) T classifications remains unclear. Our study aims to verify the impact of rib invasion on survival in patients with NSCLC through multicenter data from the Surveillance, Epidemiology, and End Results (SEER) database, and proposed a more appropriate pT for the forthcoming 9^th tumor-node-metastasis (TNM) classifications.Method: The SEER database was used to collect T_2b-4N_0-2M₀ NSCLC cases from the period of 2010-2015 according to the 7^th TNM classification system. Subsequently, the T classification was restaged according to the 8^th TNM classification system based on the following codes: tumor size and tumor extension. Cases with T1-2 disease and incomplete clinicopathological information were excluded. Finally, 6479 T3 and T4 NSCLC patients were included in the present study and divided into a rib invasion group (n = 131), other pT3 group (n = 3835), and pT4 group (n = 2513). Propensity-score matching (PSM) balanced the known confounders of the prognosis, resulting in two sets (rib invasion group vs. other pT3 and pT4 group). Overall survival (OS) and cancer-specific survival (CSS) were investigated using Kaplan-Meier survival curves, and predictive factors of OS and CSS were assessed by Cox regression.Result: Survival outcomes of the rib invasion group were worse than the other pT3 group (OS: 40.5% vs. 46.5%, p = 0.035; CSS: 49.2% vs. 55.5%, p = 0.047), but comparable to the pT4 group (OS: 40.5% vs. 39.9%, p = 0.876; CSS: 49.2% vs. 46.3%, p = 0.659). Similar results were obtained after PSM. Multivariate analyses for all patients revealed that age at diagnosis, gender, N stage, T stage, surgical modalities, and adjuvant therapy had a predictive value for the prognosis.Conclusion: The rib invasion group had a worse prognosis than the other pT3 groups, but was similar to the pT4 group. Our recommendation is to change the classification of rib invasion to pT4 disease and further validate this in the forthcoming 9^th TNM classification.

Background. Ubiquitination is an important regulator in physiological and pathological conditions. Ubiquitin‐specific protease 2 (USP2), as a member of the USP family, exhibits oncogenic effects in multiple malignancies. However, the exact role of USP2 has not been well clarified in lung cancer pathogenesis and progression. Therefore, we aimed to further investigate the regulatory roles of USP2 in lung cancer in this study. Methods. Firstly, immunoprecipitation‐Mass Spectrometry (IP‐MS), Co‐immunoprecipitation (Co‐IP), combined with immunofluorescent colocalization method, was conducted for USP2 protein interaction analysis in lung cancer cell lines. qRT‐PCR, Western blot, and immunohistochemistry assays explored the USP2 expression pattern and USP2/ARID2‐ (AT‐rich interactive domain 2‐) specific shRNAs and overexpression vectors. Co‐IP assays were designed to validate USP2‐ARID2 protein interaction. Further functional studies including CHX chase assay, transwell assay, and wound healing assay were subsequently applied to evaluate the impact of USP2 modulation on lung cancer cells. Results. USP2 suppression was characteristic in lung cancer cell line models and lung cancer samples. USP2 and ARID2 demonstrated protein‐protein interaction and overlapping localization in cancer cell models. Functional experiments suggested USP2 inhibited lung cancer cell invasion and migration by reducing ARID2 protein degradation. Subsequent ubiquitination assays indicated ARID2 protein degradation via the ubiquitination was significantly reduced by USP2 interaction. Conclusions. Our study provided novel insight that USP2 might suppress lung cancer by reducing ARID2 protein degradation via ubiquitination.

Hepatocellular carcinoma (HCC) ranks among the five most common cancer entities worldwide and leads to hundred-thousands of deaths every year. Despite some groundbreaking therapeutical revelations during the last years, the overall prognosis remains poor. Although the immune system fights malignant transformations with a robust anti-tumor response, certain immune mediators have also been shown to promote cancer development. For example, interleukin (IL)-22 has been associated with HCC progression and worsened prognosis in multiple studies. However, the underlying mechanisms of the pathological role of IL-22-signaling as well as the role of its natural antagonist IL-22 binding protein (IL-22BP) in HCC remain elusive. Here, we corroborate the pathogenic role of IL-22 in HCC by taking advantage of two mouse models. Moreover, we observed a protective role of IL-22BP during liver carcinogenesis. While IL-22 was mainly produced by CD4⁺ T cells in HCC, IL-22BP was abundantly expressed by neutrophils during liver carcinogenesis. Hepatocytes could be identified as a major target of this pathological IL-22-signaling. Moreover, abrogation of IL-22 signaling in hepatocytes in IL22ra1^flox/flox × Alb^Cre+ mice reduced STEAP4 expression-a known oncogene-in HCC in vivo. Likewise, STEAP4 expression correlated with IL22 levels in human HCC samples, but not in healthy liver specimens. In conclusion, these data encourage the development of therapeutical approaches that target the IL-22–IL-22BP axis in HCC.

Background. Bone metastasis (BM) has been proven to be responsible for the poor prognosis of primary malignant bone neoplasms (PMBNs). We aimed to identify the prevalence, risk factors, and prognostic factors for PMBNs patients with BM based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods. 4,758 patients diagnosed with PMBNs from 2010 to 2018 were selected from the SEER database. All patients were divided into two groups: the BM group or the non-BM group. Pearson’s chi-square test and Fisher’s exact method were used to assess baseline characteristics, and logistic regression analysis was applied to assess risk factors. In addition, a nomogram was constructed based on the results of Cox regression analysis among 227 patients with BM. The good performance and clinical applicability of the nomogram were tested by the concordance index, operating characteristic curve, area under the curve, calibration curves, and decision curve analysis. Results. 227 (4.8%) patients had metastasis to bone at diagnosis. Primary site outside the extremities (axial: odds ratio, OR = 1.770 ; others: OR = 1.951 ), Ewing sarcoma ( OR = 2.845 ), larger tumor size (5–8 cm: OR = 3.403 ; >8 cm: OR = 5.562 ), tumor extension beyond the periosteum ( OR = 2.477 ), and regional lymph node metastasis ( OR = 2.900 ) were associated with a higher risk of BM at the initial diagnosis of PMBNs. Five independent prognostic factors were found in the survival analysis: pathological type (chondrosarcoma vs. osteosarcoma: hazard ratio, HR = 0.342 ; Ewing sarcoma vs. osteosarcoma: HR = 0.592 ; and chordoma vs. osteosarcoma: HR = 0.015 ), marital status ( HR = 2.457 ), pulmonary metastasis ( HR = 1.934 ), surgery at the primary site ( HR = 0.164 ), and chemotherapy ( HR = 0.084 ). A nomogram based on these prognostic factors could be a good predictor of cancer-specific survival. Conclusions. We identified the prevalence, risk factors, and prognostic factors correlated with BM in PMBNs patients. The related nomogram could be a practical tool for therapeutic decision-making and individual counseling.

Introduction: The current American Joint Committee on Cancer (AJCC) M1a staging of non‐small cell lung cancer (NSCLC) encompasses a wide disease spectrum, showing diverse prognosis.Methods: Patients who diagnosed in an earlier period formed the training cohort, and those who diagnosed thereafter formed the validation cohort. Kaplan–Meier analysis was performed for the training cohort by dividing the M1a stage into three subgroups: (I) malignant pleural effusion (MPE) or malignant pericardial effusion (MPCE); (II) separate tumor nodules in contralateral lung (STCL); and (III) pleural tumor nodules on the ipsilateral lung (PTIL). Gender, age, histologic, N stage, grade, surgery for primary site, lymphadenectomy, M1a groups, and chemotherapy were selected as independent prognostic factors using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. And a nomogram was constructed using Cox hazard regression analysis. Accuracy and clinical practicability were separately tested by Harrell's concordance index, the receiver operating characteristic (ROC) curve, calibration plots, residual plot, the integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA).Results: The concordance index (0.661 for the training cohort and 0.688 for the validation cohort) and the area under the ROC curve (training cohort: 0.709 for 1‐year and 0.727 for 2‐year OS prediction; validation cohort: 0.737 for 1‐year and 0.734 for 2‐year OS prediction) indicated satisfactory discriminative ability of the nomogram. Calibration curve and DCA presented great prognostic accuracy, and clinical applicability. Its prognostic accuracy preceded the AJCC staging with evaluated NRI (1‐year: 0.327; 2‐year: 0.302) and IDI (1‐year: 0.138; 2‐year: 0.130).Conclusion: Our study established a nomogram for the prediction of 1‐ and 2‐year OS in patients with NSCLC diagnosed with stage M1a, facilitating healthcare workers to accurately evaluate the individual survival of M1a NSCLC patients. The accuracy and clinical applicability of this nomogram were validated.

The clearance of apoptotic cells by Mφs favors malignant pleural effusion progression in a murine cancer model.

There is no conclusion about the most important contributor to the upswing of locally advanced colorectal cancer (LACRC) survival. Data from the Surveillance, Epidemiology, and End Results (SEER) database was extracted to identify colorectal adenocarcinoma cancer patients at stage II and III diagnosed in the two periods 1989–1990 and 2009–2010. The statistical methods included Pearson’s chi-squared test, log-rank test, Cox regression model and propensity score matching. The Cox regression model showed that hazard ratio (HR) of non-surgery dropped from 11.529 to 3.469 in right colon cancer (RCC), 5.214 to 2.652 in left colon cancer (LCC) and 3.275 to 3.269 in rectal cancer (RC) from 1989–1990 to 2009–2010. The 95% confidence intervals (CIs) for surgical resection in 2009–2010 were narrower than those in 1989–1990. HR became greater in LACRC without chemotherapy (from 1.337 to 1.779 in RCC, 1.269 to 2.017 in LCC, 1.317 to 1.811 in RC). There was no overlapping about the 95% CI of chemotherapy between the two groups. The progress of surgery was not linked to the improvement of overall survival (OS) of RCC (p = 0.303) and RC (p = 0.660). Chemotherapy had a significant association with OS of all colorectal cancer (CRC) patients (p = 0.017 in RCC; p = 0.006 in LCC; p = 0.001 in RC). Advancements in chemotherapy regimen were the main contributor to the upswing of CRC survival. The improvements in surgery had a limited effect on improvements in CRC survival.