Sequential Shrinkage Estimate for COX Regression Models with Uncertain Number of Effective Variables

In the applications of COX regression models, we always encounter data sets that contain too many variables that only a few of them contribute to the model. Therefore, it will waste much more samples to estimate the “noneffective” variables in the inference. In this paper, we use a sequential procedure for constructing the fixed size confidence set for the “effective” parameters to the model based on an adaptive shrinkage estimate such that the “effective” coefficients can be efficiently identified with the minimum sample size. Fixed design is considered for numerical simulation. The strong consistency, asymptotic distributions and convergence rates of estimates under the fixed design are obtained. In addition, the sequential procedure is shown to be asymptotically optimal in the sense of Chow and Robbins (1965).

Stratified Cox Regression Analysis of Survival under CIMAvax^(■)EGF Vaccine

Background: The Center of Molecular Immunology (CIM) is a center in Cuba devoted to the research, development and manufacturing of biotechnological products. CIMAvax?EGF is a vaccine for the treatment of non-small cell lung cancer patients (NSCL). Purpose: The aim of this work is to evaluate the effects of some potential prognostic factors on the overall survival of patients treated with CIMAvax?EGF vaccine, based on data collected in a phase II and a phase III clinical trials. Methods: The stratified Cox regression model is used to evaluate the effects of these prognostic factors, based on separate analysis for each trial, and on the combined data from both trials. Results: Patients with Performance status 0 or 1, with IV stage of tumor and male under 60 years obtain more benefit in terms of overall survival if they receive CIMAvax?EGF. Conclusions: Vaccinated group has a better performance if patients have a performance status 0 or 1, stage IV and age under 60 years. These prognostic factors influence overall survival in a positive way for those patients that received CIMAvax?EGF.

The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

Retrospective analysis of clinical characteristics and prognostic factors for pathologic fracture in 44 patients with extremity osteosarcoma

Objective: The aim of this study was to identify the clinical features and prognostic factors associated with extremity osteosarcoma with pathologic fracture. Methods: The clinical records of 271 patients with extremity osteosarcomas were retrospectively reviewed. The data obtained covered the period from October 2003 to May 2012, and included sex, age, tumor site etc. The mean follow-up time was 25.2 months(ranged from 1 to 117). Chi-square method and Kaplan-Meier method were used to compare clinical differences and overall survival between patients with or without pathologic fracture, respectively. The univariate analysis was used to determine the prognostic factors related with survival rate by log-rank test. The multivariate analysis of prognosis was performed by COX proportional hazards regression model. Results: The proportions of patients having a tumor's diameter of 10 cm or more(P = 0.038), locating upper limbs(P = 0.004) and receiving amputation surgery(P = 0.02) were significantly higher with pathological fracture group than without pathological fracture group. The local recurrence rate(P = 0.000) was also significantly higher in the pathological fracture group. The median survival time of patients with or without pathological fracture was 16(95% confidence interval: 14.6–17.4) months and 22(95% confidence interval: 19.8–24.1) months(P = 0.002). The Log-rank univariate analysis indicated that the tumor size, Enneking's surgical staging, Karnofsky performance status(KPS) score, cycles of adjuvant chemotherapy, local recurrence and metastasis were significantly related to overall survival. Multivariate Cox regression analysis revealed KPS score, cycles of adjuvant chemotherapy and metastasis were independent prognostic factors(P < 0.05). Conclusion: Compared with the patients without pathological fracture, a higher proportion of patients receiving amputation surgery or having larger tumor size, humeral osteosarcoma or local recurrence was observed in patients with pathological fracture, and the prognosis of these patients was poor. The independent prognostic factors of extremity osteosarcoma with pathologic fracture were the KPS score, cycles of adjuvant chemotherapy and metastasis.

Transcriptomic analysis reveals key lnc RNAs associated with ribosomal biogenesis and epidermis differentiation in head and neck squamous cell carcinoma

Objective： In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma （HNSCC）-associated long noncoding RNAs （IncRNAs）, and to discover potential IncRNA prognostic biomarkers for HNSCC based on next-generation RNA-seq. Methods： RNA-seq data of 546 samples from patients with HNSCC were downloaded from The Cancer Genome Atlas （TCGA）, including 43 paired samples of tumor tissue and adjacent normal tissue. An integrated analysis incorporating differential expression, weighted gene co-expression networks, functional enrichment, clinical parameters, and survival analysis was conducted to discover HNSCC-associated IncRNAs. The function of CYTOR was verified by cell-based experiments. To further identify IncRNAs with prognostic significance, a multivariate Cox proportional hazard regression analysis was performed. The identified IncRNAs were validated with an independent cohort using clinical feature relevance analysis and multivariate Cox regression analysis. Results： We identified nine HNSCC-relevant IncRNAs likely to play pivotal roles in HNSCC onset and development. By functional enrichment analysis, we revealed that CYTOR might participate in the multistep pathological processes of cancer, such as ribosome biogenesis and maintenance of genomic stability. CY-I-OR was identified to be positively correlated with lymph node metastasis, and significantly negatively correlated with overall survival （OS） and disease free survival （DFS） of HNSCC patients. Moreover, CYTOR inhibited cell apoptosis following treatment with the chemotherapeutic drug diamminedichloroplatinum （DDP）. HCG22, the most dramatically down-regulated IncRNA in tumor tissue, may function in epidermis differentiation. It was also significantly associated with several clinical features of patients with HNSCC, and positively correlated with patient survival. CYTOR and HCG22 maintained their prognostic values in- dependent of several clinical features in multivariate Cox hazards analysis. Notably, validation either based on an independent HNSCC cohort or by laboratory experiments confirmed these findings. Conclusions： Our transcriptomic analysis suggested that dysregulation of these HNSCC-associated IncRNAs might be involved in HNSCC oncogenesis and progression. Moreover, CYTOR and HCG22 were confirmed as two independent prognostic factors for HNSCC patient survival, providing new insights into the roles of these IncRNAs in HNSCC as well as clinical applications.