C-X-C chemokine receptor 4 (CXCR4) is frequently over-expressed in various types of cancer; many agents against CXCR4 are in clinical development currently despite variable data for the prognostic impact of CXCR4 expression. Here eighty-five studies with a total of 11,032 subjects were included to explore the association between CXCR4 and progression-free survival (PFS) or overall survival (OS) in subjects with cancer. Pooled analysis shows that CXCR4 over-expression is significantly associated with poorer PFS (HR 2.04; 95% CI, 1.72-2.42) and OS (HR=1.94; 95% CI, 1.71-2.20) irrespective of cancer types. Subgroup analysis indicates significant association between CXCR4 and shorter PFS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, renal cancer, gynecologic cancer, pancreatic cancer and liver cancer; the prognostic effects remained consistent across age, risk of bias, levels of adjustment, median follow-up period, geographical area, detection methods, publication year and size of studies. CXCR4 over-expression predicts unfavorable OS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, head and neck cancer, renal cancer, lung cancer, gynecologic cancer, liver cancer, prostate cancer and gallbladder cancer; these effects were independence of age, levels of adjustment, publication year, detection methods and follow-up period. In conclusion, CXCR4 over-expression is associated with poor prognosis in cancer.

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Microtubule-associated protein 1 light chain 3B (LC3B) was involved in autophagosome formation and had been as a marker of autophagy which played an important role in the development of breast cancer. The purpose of this study was to explore the level of LC3B expression in four stages of triple-negative breast cancer (TNBC) and to evaluate the prognostic significance of LC3B expression in TNBC. The ultimate aim was to identify the new factor that could be useful in predicting clinical behavior of TNBC. We evaluated the expression level of LC3B protein in four kinds of TNBC tissue samples, including intraductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) without metastases, IDC with lymph node metastases (LNM), and IDC with distant metastases (DM). Hundred and four primary TNBC patients were involved in present study, and the expression level of LC3B protein was assessed by immunohistochemistry. Medical records of these patients were reviewed, and the clinicopathological analysis was performed. High expression of LC3B was observed in 7.7 % of DCIS (1 of 13 cases), 16.2 % of IDC (6 of 37 cases), 35.7 % of LNM (15 of 42 cases), and 58.3 % of DM (7 of 12 cases). LC3B high expression was significantly associated with tumor size (P = 0.028), lymph node metastasis (P = 0.002), and Ki-67 expression (P = 0.047). LC3B high expression patients showed poorer DFS and OS rates compared with LC3B low expression patients (P = 0.024, and P = 0.047, respectively). Multivariate analyses confirmed that high LC3B expression was an independent and significant factor for predicting the poor outcome of TNBC patients. These preliminary results demonstrated that high LC3B expression was associated with lymph node and distant metastasis. Furthermore, high LC3B protein expression was correlated with shorter survival in patients with triple-negative breast carcinoma. These findings provided preliminary evidence for the function of LC3B on the progression of TNBC and suggested LC3B was a useful marker in prognostic evaluation for patients with TNBC.

Background: Inhibitors targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have unprecedented effects in cancer treatment. However, the objective response rates (ORRs), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 blockade monotherapy have not been systematically evaluated. Methods: We searched Embase, PubMed, and Cochrane database from inception to July 2019 for prospective clinical trials on single-agent PD-1/PD-L1 antibodies (avelumab, atezolizumab, durvalumab, cemiplimab, pembrolizumab, and nivolumab) with information regarding ORR, PFS, and OS. Results: Totally, 28,304 patients from 160 perspective trials were included. Overall, 4747 responses occurred in 22,165 patients treated with PD-1/PD-L1 monotherapy [ORR, 20.21%; 95% confidence interval (CI), 18.34–22.15%]. Compared with conventional therapy, PD-1/PD-L1 blockade immunotherapy was associated with more tumor responses (odds ratio, 1.98; 95% CI, 1.52–2.57) and better OS [hazard ratio (HR), 0.75; 95% CI, 0.67–0.83]. The ORRs varied significantly across cancer types and PD-L1 expression status. Line of treatment, clinical phase and drug target also impacted the response rates in some tumors. A total of 2313 of 9494 PD-L1 positive patients (ORR, 24.39%; 95% CI, 22.29–26.54%) and 456 of 4215 PD-L1 negative patients (ORR, 10.34%; 95% CI, 8.67–12.14%) achieved responses. For PD-L1 negative patients, the ORR (odds ratio, 0.92; 95% CI, 0.70–1.20) and PFS (HR, 1.15; 95% CI, 0.87–1.51) associated with immunotherapy and conventional treatment were similar. However, PD-1/PD-L1 blockade monotherapy decreased the risk of death in both PD-L1 positive (HR, 0.66; 95% CI, 0.60–0.72) and PD-L1 negative (HR, 0.86; 95% CI, 0.74–0.99) patients compared with conventional therapy. Conclusion: The efficacies associated with PD-1/PD-L1 monotherapy vary significantly across cancer types and PD-L1 expression. This comprehensive summary of clinical benefit from immunotherapy in cancer patients provides an important guide for clinicians.

Glioblastoma (GBM) is the most common and most aggressive central nervous system tumor in adults. Due to GBM cell invasiveness and resistance to chemotherapy, current medical interventions are not satisfactory, and the prognosis for GBM is poor. It is necessary to investigate the underlying mechanism of GBM metastasis and drug resistance so that more effective treatments can be developed for GBM patients. sushi repeat-containing protein, X-linked 2 (SRPX2) is a prognostic biomarker in many different cancer cell lines and is associated with poor prognosis in cancer patients. SRPX2 overexpression promotes interactions between tumor and endothelial cells, leading to tumor progression and metastasis. We hypothesize that SRPX2 also contributes to GBM chemotherapy resistance and metastasis. Our results revealed that GBM tumor samples from 42 patients expressed higher levels of SRPX2 than the control normal brain tissue samples. High-SRPX2 expression levels are correlated with poor prognosis in those patients, as well as resistance to temozolomide in cultured GBM cells. Up-regulating SRPX2 expression in cultured GBM cell lines facilitated invasiveness and migration of GBM cells, while down-regulating SRPX2 through RNA interference was inhibitory. These results suggest that SRPX2 plays an important role in GBM metastasis. Epithelial to mesenchymal transition (EMT) is one of the processes that facilitate GBM metastasis and resistance to chemotherapy. EMT marker expression was decreased in SRPX2 down-regulated GBM cells, and MAPK signaling pathway marker expression was also decreased when SRPX2 is knocked down in GBM-cultured cells. Blocking the MAPK signaling pathway inhibited GBM metastasis but did not inhibit cell invasion and migration in SRPX2 down-regulated cells. Our results indicate that SRPX2 facilitates GBM metastasis by enhancing the EMT process via the MAPK signaling pathway.