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Abstract Pancreatic ductal adenocarcinoma (PDAC) presents a clinical challenge due to its poor prognosis and high mortality rate. Here, we aimed to enhance the prognostic prediction of patients with PDAC by studying collagen features in tumor microenvironment using multiphoton microscopy (MPM) combining with image processing technique. We identified eight distinct tumor-associated collagen signatures (TACS1-8) from multiphoton images of PDAC tissues and developed an optical biomarker, TACS-score, based on the TACS1-8 using ridge regression analysis. Additionally, we also extracted 142 microscopic TACS (M-TACS) from second-harmonic generation (SHG) images and constructed a new robust biomarker, M-TACS-score, using the least absolute shrinkage and selection operator (LASSO) regression analysis. Our statistical results demonstrate that as two new optical biomarkers, TACS- and M-TACS-score, are independent prognostic factors and have good discriminatory ability (high AUC) as well as risk stratification (high HR) comparing with traditional clinical model (combining seven clinical risk factors, age, sex, TNM stage, tumor location and differentiation, perineural and lymph-vascular invasion) in predicting overall survival (OS) of patients with PDAC, highlighting their potential prognostic and predictive value. A combination of label-free multiphoton imaging technique and computer-aided image processing method may offer a novel and promising approach for finding new biomarkers to improve prognosis prediction and thereby tailor treatment strategies more effectively.

Abstract Recent studies indicate that CISD3 is crucial in mitochondrial function and tumorigenesis. Using various databases, we systematically analyzed its expression, prognostic value, and immune activity. Our findings show CISD3 is mainly expressed in tumor cells across cancers, with higher mRNA but lower protein levels, degraded post-translationally via the lysosomal pathway. In certain cancers, CISD3 expression is positively correlated with tumor-infiltrating immune cells. Prognostic analysis suggests dual roles as both protective and risk factors, notably an independent prognostic predictor in renal cell carcinoma (RCC). CISD3 copy number variations are linked to homologous recombination defects and tumor-specific neoantigens, negatively correlated with methylation levels. Pathway analysis reveals CISD3 involvement in oncogenic processes, such as proliferation inhibition and epithelial-mesenchymal transition. Protein interactions underline its role in mitochondrial metabolism and redox balance. Experiments confirm low CISD3 expression in cancers, with overexpression reducing proliferation, migration, invasion, and tumor growth in mice. Mechanistic studies indicate CISD3 overexpression disrupts mitochondrial function, increases ROS levels, decreases GSH/GSSG ratios and mitochondrial membrane potential, inhibiting antioxidant activity and promoting cell damage and ferroptosis, thus impeding cancer progression. This study highlights CISD3’s potential as a prognostic biomarker and therapeutic target.

Abstract Tumor cells promote malignant behaviors such as proliferation, invasion, and metastasis of cancer cells through glucose metabolic reprogramming, but the role of the H-dependent sugar cotransporter SLC45A4 in regulating metabolic reprogramming in ovarian cancer (OC) remains largely unknown. This study aimed to investigate the effects of SLC45A4 silencing on the transcriptome spectrum of ovarian cancer cells (OCC), glucose uptake, lactic acid production, intracellular ATP levels, and the expression and activity of HIF-α glycolysis signaling pathway. The results showed that SLC45A4 is overexpressed in OC and its elevated expression correlates with adverse clinical outcomes in OC patients. Silencing of SLC45A4 significantly inhibited the proliferation, invasion, and metastasis of OCC by suppressing glucose uptake and glycolysis, and it also reduced the expression of HIF-α glycolysis signaling pathway in OC tissues. In vivo experiments using shRNA to knock down SLC45A4 in xenograft models in nude mice demonstrated a significant inhibition of tumor growth. These findings suggest that SLC45A4 silencing can restrain the malignant progression of OC by inhibiting glucose uptake in OCC and affecting the reprogramming of glycolytic energy metabolism, indicating that SLC45A4 may serve as a potential therapeutic target for OC intervention.

IntroductionInvasive Stratified Mucin-producing Carcinoma (ISMC) of the cervix is a newly named cervical adenocarcinoma associated with Human Papilloma virus (HPV). Due to its relative rarity, clinical data, pathological features, and molecular characteristics of ISMC are still under exploration. This study aims to retrospectively analyze the clinical data and pathological features of ISMC patients, summarizing the clinical and pathological morphological characteristics of ISMC. Immunohistochemistry for SLC7A11, SLC3A2, and PD-L1 will be performed on tumor tissues from ISMC patients to preliminarily explore potential therapeutic targets for ISMC.MethodsWe retrospectively reviewed the electronic medical records and pathological slides of 22 ISMC patients, and performed immunohistochemical staining for solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2), and programmed death-ligand 1 (PD-L1).ResultsThe patients were aged between 31 and 70 years old. The most common symptoms were abnormal vaginal bleeding and unusual vaginal discharge. HPV testing indicated that the infection rate of HPV type 18 was the highest. All patients underwent extensive hysterectomy and pelvic lymph node dissection. The progression-free survival (PFS) ranged from 3 to 112 months, with a postoperative recurrence rate of 22.7% (5/22). ISMC exhibited diverse characteristic microstructures. Immunohistochemistry results showed that the positive rates of SLC7A11 and SLC3A2 were both 91.0% (20/22). The staining intensity of SLC7A11 in frequent ISMC recurrence cases was significantly stronger than in non-recurrent ISMC cases. PD-L1 positivity was observed in 86.4% (19/22) of cases, defined as having a Combined Positive Score(CPS)≥1.DiscussionISMC demonstrates a high rate of lymph node metastasis and a high recurrence rate, indicating strong invasiveness. Additionally, ISMC exhibits a wide morphological spectrum. SLC7A11, SLC3A2, and PD-L1 are all highly expressed in ISMC tissues. The high expression of SLC7A11 may indicate a high recurrence rate for ISMC. Immunotherapy with checkpoint inhibitors and iron death-related treatments show potential in the treatment of ISMC, with SLC7A11, SLC3A2, and PD-L1 serving as potential therapeutic targets for ISMC.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest types of cancer, and it will be meaningful to search for new biomarkers with prognostic value to help clinicians tailor therapeutic strategies. Methods Here we tried to use an advanced optical imaging technique, multiphoton microscopy (MPM) combining second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging, for the label-free detection of PDAC tissues from a cohort of 149 patients. An automated image processing method was used to extract collagen features from SHG images and the Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the prognostic value of collagen signatures. Results SHG images clearly show the different characteristics of collagen fibers in tumor microenvironment. We gained eight collagen morphological features, and a Feature-score was derived for each patient by the combination of these features using ridge regression. Statistical analyses reveal that Feature-score is an independent factor, and can predict the overall survival of PDAC patients as well as provide well risk stratification. Conclusions SHG imaging technique can potentially be a tool for the accurate diagnosis of PDAC, and this optical biomarker (Feature-score) may help clinicians make more approximate treatment decisions.

Abstract Background The histological grade is an important factor in the prognosis of invasive breast cancer and is vital to accurately identify the histological grade and reclassify of Grade2 status in breast cancer patients. Methods In this study, data were collected from 556 invasive breast cancer patients, and then randomly divided into training cohort (n = 335) and validation cohort (n = 221). All patients were divided into actual low risk group (Grade1) and high risk group (Grade2/3) based on traditional histological grade, and tumor-infiltrating lymphocyte score (TILs-score) obtained from multiphoton images, and the TILs assessment method proposed by International Immuno-Oncology Biomarker Working Group (TILs-WG) were also used to differentiate between high risk group and low risk group of histological grade in patients with invasive breast cancer. Furthermore, TILs-score was used to reclassify Grade2 (G2) into G2 /Low risk and G2/High risk. The coefficients for each TILs in the training cohort were retrieved using ridge regression and TILs-score was created based on the coefficients of the three kinds of TILs. Results Statistical analysis shows that TILs-score is significantly correlated with histological grade, and is an independent predictor of histological grade (odds ratio [OR], 2.548; 95%CI, 1.648–3.941; P 0.05 in the univariate analysis). Moreover, the risk of G2/High risk group is higher than that of G2/Low risk group, and the survival rate of patients with G2/Low risk is similar to that of Grade1, while the survival rate of patients with G2/High risk is even worse than that of patients with G3. Conclusion Our results suggest that TILs-score can be used to predict the histological grade of breast cancer and potentially to guide the therapeutic management of breast cancer patients.

Abstract Our previous studies have shown that upregulation of SLC7A1 in epithelial ovarian cancer (EOC) tumor cells significantly increases cancer cell proliferation, migration, and cisplatin resistance; however, the molecular mechanism by which SLC7A1 functions in EOC remains unknown. In later studies, we found that SLC7A1 is also highly expressed in the interstitial portion of high‐grade serous ovarian cancer (HGSOC), but the significance of this high expression in the interstitial remains unclear. Here, we showed the Interstitial high expression of SLC7A1 in HGSOC by immunohistochemistry. SLC7A1 enriched in cancer‐associated fibroblasts (CAFs) was upregulated by TGF‐β1. Transwell assay, scratch assay, cck8 assay and cell adhesion assay showed that SLC7A1 highly expressed in CAFs promoted tumor cells invasion, migration and metastasis in vitro. The effect of SLC7A1 on MAPK and EMT pathway proteins in ovarian cancer (OC) was verified by RNA sequencing and western blotting. Overexpression of SLC7A1 in OC is involved in MAPK/ ERK pathway and EMT. In general, in HGSOC, CAFs overexpressing SLC7A1 supported the migration and invasion of tumor cells; SLC7A1 is highly expressed in ovarian cancer and is involved in ERK phosphorylation and EMT signaling in MAPK signaling pathway. This suggests that SLC7A1 may be a potential therapeutic target for OC metastasis.

The tumor microenvironment (TME) is now recognized as an important participant of tumor progression. As the most abundant extracellular matrix component in TME, collagen plays an important role in tumor development. The imaging study of collagen morphological feature in TME is of great significance for understanding the state of tumor. Multiphoton microscopy (MPM), based on second harmonic generation (SHG) and two-photon excitation fluorescence (TPEF), can be used to monitor the morphological changes of biological tissues without labeling. In this study, we used MPM for large-scale imaging of early invasive breast cancer from the tumor center to normal tissues far from the tumor. We found that there were significant differences in collagen morphology between breast cancer tumor boundary, near tumor transition region and normal tissues far from the tumor. Furthermore, the morphological feature of eight collagen fibers was extracted to quantify the variation trend of collagen in three regions. These results may provide a new perspective for the optimal negative margin width of breast-conserving surgery and the understanding of tumor metastasis.

By introducing a circular Dammann grating (CDG) into the pump unit, we demonstrated an endpumped Nd:YAG laser that emitted a vortex and first-order LG mode with high laser efficiency and high power. In our scheme, the CDG was used to reshape the pumping light into an annular profile, and the adaptation of it was realized easily by inserting it into the pump unit of a conventional end-pumped solid-state laser; the laser cavity was simple, compact, and consisted of only a laser crystal and an output coupler. The beam power of this laser reached 1.86 W at an absorbed pump power of 6.38 W with a slope efficiency of 34.5%. [ABSTRACT FROM AUTHOR]