Intraperitoneal-Free Cancer Cells Represent a Major Prognostic Factor in Colorectal Peritoneal Carcinomatosis

CD44, a surface marker for cancer stem cells, interacts with PKM2, a key regulator of aerobic glycolysis, and enhances the glycolytic phenotype of cancer cells leading to antioxidant protection and macromolecules’ synthesis. To clarify the clinical importance of this “cross-talk” as a mechanism of drug resistance, we assessed the expression both of PKM2 and of CD44 in cancer cells of patients with epithelial ovarian cancer (EOC) treated with platinum-based treatment. One hundred and seventy-one patients with EOC were assessed for PKM2mRNA expression and PKM2 and CD44 proteins detection. Associations with progression-free survival (PFS) and overall survival (OS) were assessed with Kaplan–Meier and adjusted Cox regression models. PKM2mRNA and protein as well as CD44 protein were detectable in the majority of patients. Positive correlation between PKM2 and CD44 protein expression was observed (Spearman rho = 0.2, p = 0.015). When we used the median to group patients into high versus low expression, high PKM2mRNA and protein levels were significantly associated with lower progression-free survival (PFS; p = 0.003 and p = 0.002, respectively) and shorter overall survival (OS; p ≤ 0.001 and p = 0.001, respectively). However, high CD44 protein expression was significantly correlated only with shorter OS (p = 0.004). Moreover, patients with both high PKM2 and CD44 protein levels experienced shorter PFS and OS (p = 0.007 and p = 0.003, respectively) compared to patients with low expression of both proteins. Finally, higher PKM2mRNA and protein expression as well as CD44 protein expression (HR: 2.16; HR: 1.82; HR: 1.01, respectively) were independent prognostic factors for decreased median OS (mOS), whereas only PKM2 protein expression (HR: 1.95) was an independent prognostic factor for decreased median PFS (mPFS). In conclusion, PKM2 expression is a negative prognostic factor in EOC patients, but the interaction between CD44 and PKM2 that may be implicated in EOC platinum-resistance needs further investigation.

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Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21197025 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7025

Author(s):

Katarzyna Ratajczak-Wielgomas ◽

Alicja Kmiecik ◽

Jedrzej Grzegrzołka ◽

Aleksandra Piotrowska ◽

Agnieszka Gomulkiewicz ◽

...

Keyword(s):

Lung Cancer ◽

Prognostic Factor ◽

Small Cell Lung Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Cell Lung Cancer ◽

Prognostic Significance ◽

Immunohistochemical Analysis ◽

Small Cell ◽

Small Cell Lung

Background: The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. Materials and Methods: Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. Results: Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. Conclusions: POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.

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Intraperitoneal free cancer cells in gastric cancer: pathology of peritoneal carcinomatosis and rationale for intraperitoneal chemotherapy/hyperthermic intraperitoneal chemotherapy in gastric cancer

Translational Gastroenterology and Hepatology ◽

10.21037/tgh.2016.08.03 ◽

2016 ◽

Vol 1 ◽

pp. 69-69 ◽

Cited By ~ 5

Author(s):

Zhong-He Ji ◽

Kai-Wen Peng ◽

Yan Li

Keyword(s):

Gastric Cancer ◽

Peritoneal Carcinomatosis ◽

Cancer Cells ◽

Intraperitoneal Chemotherapy ◽

Hyperthermic Intraperitoneal Chemotherapy ◽

Cancer Pathology

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Expression of Podoplanin in Sinonasal Squamous Cell Carcinoma and Its Clinical Significance

American Journal of Rhinology and Allergy ◽

10.1177/1945892420930976 ◽

2020 ◽

Vol 34 (6) ◽

pp. 800-809

Author(s):

Huan Wang ◽

Chunyan Hu ◽

Xiaole Song ◽

Li Hu ◽

Wanpeng Li ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Prognostic Factor ◽

Cell Carcinoma ◽

Cancer Cells ◽

Squamous Cell ◽

Disease Free Survival ◽

Positive Staining ◽

Primary Tumor Site ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded

Background It was recently suggested that the upregulation of podoplanin (PDPN) in cancer cells plays a significant role in tumor invasion and metastasis and that it is significantly associated with poor prognosis in oral, cutaneous, and esophageal squamous cell carcinoma. The aim of this study was to investigate the expression pattern of PDPN in sinonasal squamous cell carcinoma (SNSCC) and to evaluate its role as a prognostic factor for survival outcome. Patients and methods This study included 59 subjects with SNSCC. We retrospectively collected the clinical features of these patients from medical records and retrieved the associated formalin-fixed, paraffin-embedded tissues for PDPN immunohistochemical staining. Furthermore, PDPN expression was analyzed in relation to the patients’ clinicopathological features and prognosis. Results We observed positive staining for PDPN in both cancer cells and stromal cancer-associated fibroblasts (CAFs). Positive expression of PDPN in cancer cells of patients with SNSCC was significantly correlated with the primary tumor site (p = 0.009) and local recurrence (p = 0.024). In addition, patients with PDPN-positive cancer cells had significantly lower overall survival (OS) and disease-free survival (DFS) rates than did patients with PDPN-negative cancer cells (both p < 0.05). Multivariate analysis revealed that PDPN expression in cancer cells was an independent prognostic factor for both OS (p = 0.038) and DFS (p = 0.039). Conclusions Our findings demonstrated that PDPN overexpression may be both an independent prognostic biomarker and a therapeutic target in SNSCC.

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