45ca8f9673aaa214d820ac89a3d7cb8b pmc_10890005.pdf 0edb42a1b64575cff4b929b3ba137a12c7210873 pmc_10890005.pdf f2660e0cc08bcde92d15375e3207f17029d39b8faa00c87ee5c17587cf34cdb9 pmc_10890005.pdf Title: Influence of Tumor Stroma on the Aggressiveness of Poorly Cohesive Gastric Carcinoma Subject: Tumor-stroma crosstalk promotes the adaptation of cancer cells to the local microenvironment and sustains their growth. We assessed the quantitative and qualitative impact of intralesional stroma on clinic-pathological features and the prognosis of poorly cohesive gastric cancer (PCGC) variants. Tissue microarrays including 75 PCGC specimens were immunostained for cytokeratin 8/18 and -smooth muscle actin to assess the relative proportion of neoplastic cells versus stromal components and the cases were subsequently divided into stroma-rich (SR) and stroma-poor (SP) tumors. Stromal status is significantly associated with the depth of tumor invasion. Patient survival rate was found to be higher in the SP compared to the SR tumor group and, hence, abundant stroma was identified as a significant risk factor in univariable analysis but had no independent prognostic impact. We also investigated the mRNA levels of KRT8 and the associated transcriptional signatures using the molecular data of 82 PCGC cases divided into KRT8-high and KRT8-low groups. KRT8-high tumors were enriched in proteins localized in the extracellular compartment and their expression levels correlated with longer survival in the KRT8-high group and shorter overall survival in the KRT8-low group. Comprehensively, we find that relative intralesional stromal content is a marker of aggressiveness in PCGC tumors and that extracellular proteins characterize functionally and clinically different PCGC subgroups. Keywords: gastric cancer; intratumoral stroma; poorly cohesive; diffuse type Author: Giorgio Malpeli, Federica Filippini, Fabrizio Tedone, Lorena Torroni, Mariella Alloggio, Claudia Castelli, Mariagiulia Dal Cero, Roberto Perris, Anna Tomezzoli, Giovanni De Manzoni and Maria Bencivenga Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Feb 9 10:08:15 2024 CET ModDate: Fri Feb 9 10:16:28 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3092167 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CQZVIY+VnURWPalladioL Type 1 Custom yes yes yes 10 0 ZXDKIP+EURM10 Type 1 Builtin yes yes yes 16 0 KKBYEV+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 PNMKOO+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 FNTRZH+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 UIJACC+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 48 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 51 0 HPBFCD+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 78 0 HPBFCE+PalatinoLinotype CID TrueType Identity-H yes yes yes 81 0 HPBFCF+PalatinoLinotype TrueType WinAnsi yes yes no 87 0 HPBFCH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 90 0 HPBFHH+PalatinoLinotype TrueType MacRoman yes yes no 93 0 HPBFCD+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 104 0 HPBFCE+PalatinoLinotype CID TrueType Identity-H yes yes yes 107 0 HPBFCF+PalatinoLinotype TrueType WinAnsi yes yes no 113 0 HPBFCH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 116 0 HPBFHH+PalatinoLinotype TrueType MacRoman yes yes no 119 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 129 0 BFJOJL+CMSY10 Type 1 Builtin yes yes yes 134 0 HPBHFO+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 149 0 HPBHNM+Arial CID TrueType Identity-H yes yes yes 152 0 HPBFCD+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 158 0 HPBFCE+PalatinoLinotype CID TrueType Identity-H yes yes yes 161 0 HPBFCF+PalatinoLinotype TrueType WinAnsi yes yes no 167 0 HPBFCH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 170 0 HPBFHH+PalatinoLinotype TrueType MacRoman yes yes no 173 0 HPBFCD+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 192 0 HPBFCE+PalatinoLinotype CID TrueType Identity-H yes yes yes 195 0 HPBFCF+PalatinoLinotype TrueType WinAnsi yes yes no 201 0 HPBFCH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 204 0 HPBFHH+PalatinoLinotype TrueType MacRoman yes yes no 207 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-04-30 02:51:37 CEST RepresentationInformation: pmc_10890005.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-04-09 02:35:33 CEST Size: 3092167 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 357 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Samples Destination: subsection.2.1 Item: Title: Immunohistochemistry Destination: subsection.2.2 Item: Title: Gene Expression Analysis Destination: subsection.2.3 Item: Title: Statistical Methods Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Demographic, Histopathological and Clinical Characteristics at Baseline Destination: subsection.3.1 Item: Title: Long-Term Prognosis Destination: subsection.3.2 Item: Title: Enrichment in Cell Content and Predicted Function of Genes Upregulated in the KRT8-High versus KRT8-Low PCGC Groups Destination: subsection.3.3 Item: Title: Enhanced Transcription of Genes Encoding Extracellular Proteins Associated with Increased Overall Survival in the KRT8-High Group and Reduced Overall Survival in the KRT8-Low Group of PC GC Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Influence of Tumor Stroma on the Aggressiveness of Poorly Cohesive Gastric Carcinoma Author: Giorgio Malpeli, Federica Filippini, Fabrizio Tedone, Lorena Torroni, Mariella Alloggio, Claudia Castelli, Mariagiulia Dal Cero, Roberto Perris, Anna Tomezzoli, Giovanni De Manzoni and Maria Bencivenga Subject: Tumor-stroma crosstalk promotes the adaptation of cancer cells to the local microenvironment and sustains their growth. We assessed the quantitative and qualitative impact of intralesional stroma on clinic-pathological features and the prognosis of poorly cohesive gastric cancer (PCGC) variants. Tissue microarrays including 75 PCGC specimens were immunostained for cytokeratin 8/18 and -smooth muscle actin to assess the relative proportion of neoplastic cells versus stromal components and the cases were subsequently divided into stroma-rich (SR) and stroma-poor (SP) tumors. Stromal status is significantly associated with the depth of tumor invasion. Patient survival rate was found to be higher in the SP compared to the SR tumor group and, hence, abundant stroma was identified as a significant risk factor in univariable analysis but had no independent prognostic impact. We also investigated the mRNA levels of KRT8 and the associated transcriptional signatures using the molecular data of 82 PCGC cases divided into KRT8-high and KRT8-low groups. KRT8-high tumors were enriched in proteins localized in the extracellular compartment and their expression levels correlated with longer survival in the KRT8-high group and shorter overall survival in the KRT8-low group. Comprehensively, we find that relative intralesional stromal content is a marker of aggressiveness in PCGC tumors and that extracellular proteins characterize functionally and clinically different PCGC subgroups. 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